JP2021517589A - 癌の治療のための化学免疫療法を増強するためのカロリー制限模倣物の使用 - Google Patents
癌の治療のための化学免疫療法を増強するためのカロリー制限模倣物の使用 Download PDFInfo
- Publication number
- JP2021517589A JP2021517589A JP2020572608A JP2020572608A JP2021517589A JP 2021517589 A JP2021517589 A JP 2021517589A JP 2020572608 A JP2020572608 A JP 2020572608A JP 2020572608 A JP2020572608 A JP 2020572608A JP 2021517589 A JP2021517589 A JP 2021517589A
- Authority
- JP
- Japan
- Prior art keywords
- malignant
- tumor
- cancer
- cell
- adenocarcinoma
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 287
- 201000011510 cancer Diseases 0.000 title claims abstract description 104
- 235000020827 calorie restriction Nutrition 0.000 title claims abstract description 48
- 238000011342 chemoimmunotherapy Methods 0.000 title abstract description 8
- 238000011282 treatment Methods 0.000 title description 67
- ZMJBYMUCKBYSCP-UHFFFAOYSA-N Hydroxycitric acid Chemical compound OC(=O)C(O)C(O)(C(O)=O)CC(O)=O ZMJBYMUCKBYSCP-UHFFFAOYSA-N 0.000 claims abstract description 81
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 claims abstract description 81
- 238000002512 chemotherapy Methods 0.000 claims abstract description 70
- 229940063673 spermidine Drugs 0.000 claims abstract description 35
- 229940089491 hydroxycitric acid Drugs 0.000 claims abstract description 20
- 235000019136 lipoic acid Nutrition 0.000 claims abstract description 20
- 229960002663 thioctic acid Drugs 0.000 claims abstract description 20
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 claims abstract 5
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 119
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 119
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims description 117
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims description 117
- -1 benzodopa Chemical class 0.000 claims description 115
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 111
- 229960001156 mitoxantrone Drugs 0.000 claims description 107
- 210000004027 cell Anatomy 0.000 claims description 99
- 239000005557 antagonist Substances 0.000 claims description 81
- 238000000034 method Methods 0.000 claims description 77
- 239000000203 mixture Substances 0.000 claims description 70
- 239000002246 antineoplastic agent Substances 0.000 claims description 62
- 229940127089 cytotoxic agent Drugs 0.000 claims description 61
- 230000003211 malignant effect Effects 0.000 claims description 51
- 239000003112 inhibitor Substances 0.000 claims description 44
- 229960001756 oxaliplatin Drugs 0.000 claims description 39
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 38
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 35
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 34
- 229960001592 paclitaxel Drugs 0.000 claims description 33
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 30
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 30
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 29
- 201000009030 Carcinoma Diseases 0.000 claims description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 229930012538 Paclitaxel Natural products 0.000 claims description 25
- 208000009956 adenocarcinoma Diseases 0.000 claims description 24
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 24
- 229960004562 carboplatin Drugs 0.000 claims description 24
- 229960000975 daunorubicin Drugs 0.000 claims description 23
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 22
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 22
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 229960002949 fluorouracil Drugs 0.000 claims description 20
- 229960003301 nivolumab Drugs 0.000 claims description 20
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 19
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 19
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 19
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 19
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 18
- 229960004316 cisplatin Drugs 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 229960002621 pembrolizumab Drugs 0.000 claims description 18
- 229960005079 pemetrexed Drugs 0.000 claims description 18
- 229950002916 avelumab Drugs 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 229960004679 doxorubicin Drugs 0.000 claims description 17
- 229950009791 durvalumab Drugs 0.000 claims description 17
- 208000032839 leukemia Diseases 0.000 claims description 17
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 16
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 229960003668 docetaxel Drugs 0.000 claims description 16
- 229960005386 ipilimumab Drugs 0.000 claims description 16
- 108010092160 Dactinomycin Proteins 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 15
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 15
- 229960003087 tioguanine Drugs 0.000 claims description 14
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 13
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 13
- 206010039491 Sarcoma Diseases 0.000 claims description 13
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 12
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 12
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 12
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 12
- 101000882390 Homo sapiens Histone acetyltransferase p300 Proteins 0.000 claims description 12
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 12
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 12
- 229960001904 epirubicin Drugs 0.000 claims description 12
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 12
- 229960000908 idarubicin Drugs 0.000 claims description 12
- 229910052697 platinum Inorganic materials 0.000 claims description 12
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 claims description 11
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 11
- 229960003048 vinblastine Drugs 0.000 claims description 11
- 102100038885 Histone acetyltransferase p300 Human genes 0.000 claims description 10
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 10
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 10
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 claims description 10
- 108010006654 Bleomycin Proteins 0.000 claims description 9
- 239000003242 anti bacterial agent Substances 0.000 claims description 9
- 229940088710 antibiotic agent Drugs 0.000 claims description 9
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 9
- 229960000684 cytarabine Drugs 0.000 claims description 9
- 229960000640 dactinomycin Drugs 0.000 claims description 9
- 229960005277 gemcitabine Drugs 0.000 claims description 9
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 9
- 229960004768 irinotecan Drugs 0.000 claims description 9
- 201000001441 melanoma Diseases 0.000 claims description 9
- 229960001428 mercaptopurine Drugs 0.000 claims description 9
- 229960000485 methotrexate Drugs 0.000 claims description 9
- 229960004857 mitomycin Drugs 0.000 claims description 9
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 claims description 9
- 108010058566 130-nm albumin-bound paclitaxel Proteins 0.000 claims description 8
- YIMDLWDNDGKDTJ-QLKYHASDSA-N 3'-deamino-3'-(3-cyanomorpholin-4-yl)doxorubicin Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1C#N YIMDLWDNDGKDTJ-QLKYHASDSA-N 0.000 claims description 8
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 claims description 8
- CHPZKNULDCNCBW-UHFFFAOYSA-N gallium nitrate Chemical compound [Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O CHPZKNULDCNCBW-UHFFFAOYSA-N 0.000 claims description 8
- 150000004676 glycans Chemical class 0.000 claims description 8
- 229960001101 ifosfamide Drugs 0.000 claims description 8
- 229920001282 polysaccharide Polymers 0.000 claims description 8
- 239000005017 polysaccharide Substances 0.000 claims description 8
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 8
- 229960001099 trimetrexate Drugs 0.000 claims description 8
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 claims description 8
- 229950009811 ubenimex Drugs 0.000 claims description 8
- 229960004528 vincristine Drugs 0.000 claims description 8
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 8
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 8
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 7
- 102000004146 ATP citrate synthases Human genes 0.000 claims description 7
- 108090000662 ATP citrate synthases Proteins 0.000 claims description 7
- 229940123576 Acetyltransferase inhibitor Drugs 0.000 claims description 7
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 7
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 claims description 7
- 206010025323 Lymphomas Diseases 0.000 claims description 7
- 201000000053 blastoma Diseases 0.000 claims description 7
- 229960004117 capecitabine Drugs 0.000 claims description 7
- 201000008184 embryoma Diseases 0.000 claims description 7
- 229960001196 thiotepa Drugs 0.000 claims description 7
- 229950007217 tremelimumab Drugs 0.000 claims description 7
- INAUWOVKEZHHDM-PEDBPRJASA-N (7s,9s)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2r,4s,5s,6s)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1 INAUWOVKEZHHDM-PEDBPRJASA-N 0.000 claims description 6
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 claims description 6
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 6
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 claims description 6
- 206010018338 Glioma Diseases 0.000 claims description 6
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 6
- 229960002749 aminolevulinic acid Drugs 0.000 claims description 6
- 229960002756 azacitidine Drugs 0.000 claims description 6
- 229960002092 busulfan Drugs 0.000 claims description 6
- 108010075600 citrate-binding transport protein Proteins 0.000 claims description 6
- 210000003298 dental enamel Anatomy 0.000 claims description 6
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 claims description 6
- 229960005156 digoxin Drugs 0.000 claims description 6
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 claims description 6
- 208000005017 glioblastoma Diseases 0.000 claims description 6
- BTXNYTINYBABQR-UHFFFAOYSA-N hypericin Chemical compound C12=C(O)C=C(O)C(C(C=3C(O)=CC(C)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 BTXNYTINYBABQR-UHFFFAOYSA-N 0.000 claims description 6
- 229940005608 hypericin Drugs 0.000 claims description 6
- PHOKTTKFQUYZPI-UHFFFAOYSA-N hypericin Natural products Cc1cc(O)c2c3C(=O)C(=Cc4c(O)c5c(O)cc(O)c6c7C(=O)C(=Cc8c(C)c1c2c(c78)c(c34)c56)O)O PHOKTTKFQUYZPI-UHFFFAOYSA-N 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- 210000004379 membrane Anatomy 0.000 claims description 6
- SSKVDVBQSWQEGJ-UHFFFAOYSA-N pseudohypericin Natural products C12=C(O)C=C(O)C(C(C=3C(O)=CC(O)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 SSKVDVBQSWQEGJ-UHFFFAOYSA-N 0.000 claims description 6
- 229930002330 retinoic acid Natural products 0.000 claims description 6
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 6
- 229960001727 tretinoin Drugs 0.000 claims description 6
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 claims description 6
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 claims description 5
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 claims description 5
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 5
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 claims description 5
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 5
- MKQWTWSXVILIKJ-LXGUWJNJSA-N Chlorozotocin Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](C=O)NC(=O)N(N=O)CCCl MKQWTWSXVILIKJ-LXGUWJNJSA-N 0.000 claims description 5
- WDJUZGPOPHTGOT-OAXVISGBSA-N Digitoxin Natural products O([C@H]1[C@@H](C)O[C@@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@@](C)([C@H](C6=CC(=O)OC6)CC5)CC4)CC3)CC2)C[C@H]1O)[C@H]1O[C@@H](C)[C@H](O[C@H]2O[C@@H](C)[C@@H](O)[C@@H](O)C2)[C@@H](O)C1 WDJUZGPOPHTGOT-OAXVISGBSA-N 0.000 claims description 5
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 claims description 5
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims description 5
- 229920001491 Lentinan Polymers 0.000 claims description 5
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 claims description 5
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 5
- 229930183665 actinomycin Natural products 0.000 claims description 5
- 229960003896 aminopterin Drugs 0.000 claims description 5
- 229960001220 amsacrine Drugs 0.000 claims description 5
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 claims description 5
- 150000008209 arabinosides Chemical class 0.000 claims description 5
- 229940127093 camptothecin Drugs 0.000 claims description 5
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 5
- 229960003261 carmofur Drugs 0.000 claims description 5
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 5
- 229960004630 chlorambucil Drugs 0.000 claims description 5
- 229960001480 chlorozotocin Drugs 0.000 claims description 5
- WDJUZGPOPHTGOT-XUDUSOBPSA-N digitoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)CC5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O WDJUZGPOPHTGOT-XUDUSOBPSA-N 0.000 claims description 5
- 229960000648 digitoxin Drugs 0.000 claims description 5
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 5
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 5
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 claims description 5
- 229930182470 glycoside Natural products 0.000 claims description 5
- 229940015872 ibandronate Drugs 0.000 claims description 5
- 229940115286 lentinan Drugs 0.000 claims description 5
- 230000002438 mitochondrial effect Effects 0.000 claims description 5
- 229960002340 pentostatin Drugs 0.000 claims description 5
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 claims description 5
- 229950010131 puromycin Drugs 0.000 claims description 5
- 210000004500 stellate cell Anatomy 0.000 claims description 5
- 229940063683 taxotere Drugs 0.000 claims description 5
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 5
- FLWWDYNPWOSLEO-HQVZTVAUSA-N (2s)-2-[[4-[1-(2-amino-4-oxo-1h-pteridin-6-yl)ethyl-methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1C(C)N(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FLWWDYNPWOSLEO-HQVZTVAUSA-N 0.000 claims description 4
- TVIRNGFXQVMMGB-OFWIHYRESA-N (3s,6r,10r,13e,16s)-16-[(2r,3r,4s)-4-chloro-3-hydroxy-4-phenylbutan-2-yl]-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H](O)[C@@H](Cl)C=2C=CC=CC=2)C/C=C/C(=O)N1 TVIRNGFXQVMMGB-OFWIHYRESA-N 0.000 claims description 4
- NOPNWHSMQOXAEI-PUCKCBAPSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-(2,3-dihydropyrrol-1-yl)-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCC=C1 NOPNWHSMQOXAEI-PUCKCBAPSA-N 0.000 claims description 4
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 claims description 4
- BOMZMNZEXMAQQW-UHFFFAOYSA-N 2,5,11-trimethyl-6h-pyrido[4,3-b]carbazol-2-ium-9-ol;acetate Chemical compound CC([O-])=O.C[N+]1=CC=C2C(C)=C(NC=3C4=CC(O)=CC=3)C4=C(C)C2=C1 BOMZMNZEXMAQQW-UHFFFAOYSA-N 0.000 claims description 4
- PWMYMKOUNYTVQN-UHFFFAOYSA-N 3-(8,8-diethyl-2-aza-8-germaspiro[4.5]decan-2-yl)-n,n-dimethylpropan-1-amine Chemical compound C1C[Ge](CC)(CC)CCC11CN(CCCN(C)C)CC1 PWMYMKOUNYTVQN-UHFFFAOYSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 206010004593 Bile duct cancer Diseases 0.000 claims description 4
- 102100038078 CD276 antigen Human genes 0.000 claims description 4
- 101710185679 CD276 antigen Proteins 0.000 claims description 4
- SAMRUMKYXPVKPA-VFKOLLTISA-N Enocitabine Chemical compound O=C1N=C(NC(=O)CCCCCCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 SAMRUMKYXPVKPA-VFKOLLTISA-N 0.000 claims description 4
- OBMLHUPNRURLOK-XGRAFVIBSA-N Epitiostanol Chemical compound C1[C@@H]2S[C@@H]2C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 OBMLHUPNRURLOK-XGRAFVIBSA-N 0.000 claims description 4
- 229930189413 Esperamicin Natural products 0.000 claims description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 4
- 208000004463 Follicular Adenocarcinoma Diseases 0.000 claims description 4
- 208000017604 Hodgkin disease Diseases 0.000 claims description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 4
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 claims description 4
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 claims description 4
- 229930192392 Mitomycin Natural products 0.000 claims description 4
- KGTDRFCXGRULNK-UHFFFAOYSA-N Nogalamycin Natural products COC1C(OC)(C)C(OC)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=C4C5(C)OC(C(C(C5O)N(C)C)O)OC4=C3C3=O)=C3C=C2C(C(=O)OC)C(C)(O)C1 KGTDRFCXGRULNK-UHFFFAOYSA-N 0.000 claims description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 4
- BXFOFFBJRFZBQZ-QYWOHJEZSA-N T-2 toxin Chemical compound C([C@@]12[C@]3(C)[C@H](OC(C)=O)[C@@H](O)[C@H]1O[C@H]1[C@]3(COC(C)=O)C[C@@H](C(=C1)C)OC(=O)CC(C)C)O2 BXFOFFBJRFZBQZ-QYWOHJEZSA-N 0.000 claims description 4
- FYAMXEPQQLNQDM-UHFFFAOYSA-N Tris(1-aziridinyl)phosphine oxide Chemical compound C1CN1P(N1CC1)(=O)N1CC1 FYAMXEPQQLNQDM-UHFFFAOYSA-N 0.000 claims description 4
- 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 claims description 4
- 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 claims description 4
- 229960000473 altretamine Drugs 0.000 claims description 4
- BBDAGFIXKZCXAH-CCXZUQQUSA-N ancitabine Chemical compound N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 BBDAGFIXKZCXAH-CCXZUQQUSA-N 0.000 claims description 4
- 229950000242 ancitabine Drugs 0.000 claims description 4
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 4
- 229960001561 bleomycin Drugs 0.000 claims description 4
- 229960005243 carmustine Drugs 0.000 claims description 4
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 108010089438 cryptophycin 1 Proteins 0.000 claims description 4
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 claims description 4
- 108010090203 cryptophycin 8 Proteins 0.000 claims description 4
- PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 claims description 4
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 4
- NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 claims description 4
- 229950004683 drostanolone propionate Drugs 0.000 claims description 4
- 229950000549 elliptinium acetate Drugs 0.000 claims description 4
- 229950011487 enocitabine Drugs 0.000 claims description 4
- 208000010932 epithelial neoplasm Diseases 0.000 claims description 4
- 229950002973 epitiostanol Drugs 0.000 claims description 4
- LJQQFQHBKUKHIS-WJHRIEJJSA-N esperamicin Chemical compound O1CC(NC(C)C)C(OC)CC1OC1C(O)C(NOC2OC(C)C(SC)C(O)C2)C(C)OC1OC1C(\C2=C/CSSSC)=C(NC(=O)OC)C(=O)C(OC3OC(C)C(O)C(OC(=O)C=4C(=CC(OC)=C(OC)C=4)NC(=O)C(=C)OC)C3)C2(O)C#C\C=C/C#C1 LJQQFQHBKUKHIS-WJHRIEJJSA-N 0.000 claims description 4
- QSRLNKCNOLVZIR-KRWDZBQOSA-N ethyl (2s)-2-[[2-[4-[bis(2-chloroethyl)amino]phenyl]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound CCOC(=O)[C@H](CCSC)NC(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 QSRLNKCNOLVZIR-KRWDZBQOSA-N 0.000 claims description 4
- 229960000961 floxuridine Drugs 0.000 claims description 4
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 4
- 229940044658 gallium nitrate Drugs 0.000 claims description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 4
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims description 4
- DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 claims description 4
- 229950008097 improsulfan Drugs 0.000 claims description 4
- 210000002751 lymph Anatomy 0.000 claims description 4
- MQXVYODZCMMZEM-ZYUZMQFOSA-N mannomustine Chemical compound ClCCNC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CNCCCl MQXVYODZCMMZEM-ZYUZMQFOSA-N 0.000 claims description 4
- 229950008612 mannomustine Drugs 0.000 claims description 4
- 229960005485 mitobronitol Drugs 0.000 claims description 4
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 claims description 4
- 229950009266 nogalamycin Drugs 0.000 claims description 4
- KGTDRFCXGRULNK-JYOBTZKQSA-N nogalamycin Chemical compound CO[C@@H]1[C@@](OC)(C)[C@@H](OC)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=C4[C@@]5(C)O[C@H]([C@H]([C@@H]([C@H]5O)N(C)C)O)OC4=C3C3=O)=C3C=C2[C@@H](C(=O)OC)[C@@](C)(O)C1 KGTDRFCXGRULNK-JYOBTZKQSA-N 0.000 claims description 4
- 230000002611 ovarian Effects 0.000 claims description 4
- 208000004019 papillary adenocarcinoma Diseases 0.000 claims description 4
- 229960000952 pipobroman Drugs 0.000 claims description 4
- NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 claims description 4
- NUKCGLDCWQXYOQ-UHFFFAOYSA-N piposulfan Chemical compound CS(=O)(=O)OCCC(=O)N1CCN(C(=O)CCOS(C)(=O)=O)CC1 NUKCGLDCWQXYOQ-UHFFFAOYSA-N 0.000 claims description 4
- 229950001100 piposulfan Drugs 0.000 claims description 4
- 229960000624 procarbazine Drugs 0.000 claims description 4
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 4
- WOLQREOUPKZMEX-UHFFFAOYSA-N pteroyltriglutamic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(=O)NC(CCC(=O)NC(CCC(O)=O)C(O)=O)C(O)=O)C(O)=O)C=C1 WOLQREOUPKZMEX-UHFFFAOYSA-N 0.000 claims description 4
- 229960000460 razoxane Drugs 0.000 claims description 4
- BMKDZUISNHGIBY-UHFFFAOYSA-N razoxane Chemical compound C1C(=O)NC(=O)CN1C(C)CN1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-UHFFFAOYSA-N 0.000 claims description 4
- 229950006315 spirogermanium Drugs 0.000 claims description 4
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims description 4
- 229960000303 topotecan Drugs 0.000 claims description 4
- 229960001670 trilostane Drugs 0.000 claims description 4
- KVJXBPDAXMEYOA-CXANFOAXSA-N trilostane Chemical compound OC1=C(C#N)C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@@]32O[C@@H]31 KVJXBPDAXMEYOA-CXANFOAXSA-N 0.000 claims description 4
- 229960000875 trofosfamide Drugs 0.000 claims description 4
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 claims description 4
- 229960000653 valrubicin Drugs 0.000 claims description 4
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 claims description 4
- 229940053867 xeloda Drugs 0.000 claims description 4
- CGMTUJFWROPELF-YPAAEMCBSA-N (3E,5S)-5-[(2S)-butan-2-yl]-3-(1-hydroxyethylidene)pyrrolidine-2,4-dione Chemical compound CC[C@H](C)[C@@H]1NC(=O)\C(=C(/C)O)C1=O CGMTUJFWROPELF-YPAAEMCBSA-N 0.000 claims description 3
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 3
- AGNGYMCLFWQVGX-AGFFZDDWSA-N (e)-1-[(2s)-2-amino-2-carboxyethoxy]-2-diazonioethenolate Chemical compound OC(=O)[C@@H](N)CO\C([O-])=C\[N+]#N AGNGYMCLFWQVGX-AGFFZDDWSA-N 0.000 claims description 3
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims description 3
- CEIZFXOZIQNICU-UHFFFAOYSA-N Alternaria alternata Crofton-weed toxin Natural products CCC(C)C1NC(=O)C(C(C)=O)=C1O CEIZFXOZIQNICU-UHFFFAOYSA-N 0.000 claims description 3
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 3
- 229930193152 Dynemicin Natural products 0.000 claims description 3
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 3
- IVDYZAAPOLNZKG-KWHRADDSSA-N Mepitiostane Chemical compound O([C@@H]1[C@]2(CC[C@@H]3[C@@]4(C)C[C@H]5S[C@H]5C[C@@H]4CC[C@H]3[C@@H]2CC1)C)C1(OC)CCCC1 IVDYZAAPOLNZKG-KWHRADDSSA-N 0.000 claims description 3
- 108091007638 Mitochondrial pyruvate carriers Proteins 0.000 claims description 3
- 208000005890 Neuroma Diseases 0.000 claims description 3
- 229940124060 PD-1 antagonist Drugs 0.000 claims description 3
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- CGMTUJFWROPELF-UHFFFAOYSA-N Tenuazonic acid Natural products CCC(C)C1NC(=O)C(=C(C)/O)C1=O CGMTUJFWROPELF-UHFFFAOYSA-N 0.000 claims description 3
- UMILHIMHKXVDGH-UHFFFAOYSA-N Triethylene glycol diglycidyl ether Chemical compound C1OC1COCCOCCOCCOCC1CO1 UMILHIMHKXVDGH-UHFFFAOYSA-N 0.000 claims description 3
- ZYVSOIYQKUDENJ-ASUJBHBQSA-N [(2R,3R,4R,6R)-6-[[(6S,7S)-6-[(2S,4R,5R,6R)-4-[(2R,4R,5R,6R)-4-[(2S,4S,5S,6S)-5-acetyloxy-4-hydroxy-4,6-dimethyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-7-[(3S,4R)-3,4-dihydroxy-1-methoxy-2-oxopentyl]-4,10-dihydroxy-3-methyl-5-oxo-7,8-dihydro-6H-anthracen-2-yl]oxy]-4-[(2R,4R,5R,6R)-4-hydroxy-5-methoxy-6-methyloxan-2-yl]oxy-2-methyloxan-3-yl] acetate Chemical class COC([C@@H]1Cc2cc3cc(O[C@@H]4C[C@@H](O[C@@H]5C[C@@H](O)[C@@H](OC)[C@@H](C)O5)[C@H](OC(C)=O)[C@@H](C)O4)c(C)c(O)c3c(O)c2C(=O)[C@H]1O[C@H]1C[C@@H](O[C@@H]2C[C@@H](O[C@H]3C[C@](C)(O)[C@@H](OC(C)=O)[C@H](C)O3)[C@H](O)[C@@H](C)O2)[C@H](O)[C@@H](C)O1)C(=O)[C@@H](O)[C@@H](C)O ZYVSOIYQKUDENJ-ASUJBHBQSA-N 0.000 claims description 3
- USDJGQLNFPZEON-UHFFFAOYSA-N [[4,6-bis(hydroxymethylamino)-1,3,5-triazin-2-yl]amino]methanol Chemical compound OCNC1=NC(NCO)=NC(NCO)=N1 USDJGQLNFPZEON-UHFFFAOYSA-N 0.000 claims description 3
- 229950011321 azaserine Drugs 0.000 claims description 3
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 claims description 3
- 229960002286 clodronic acid Drugs 0.000 claims description 3
- 229960003901 dacarbazine Drugs 0.000 claims description 3
- 229960005237 etoglucid Drugs 0.000 claims description 3
- 150000002338 glycosides Chemical class 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 229960001330 hydroxycarbamide Drugs 0.000 claims description 3
- 229950009246 mepitiostane Drugs 0.000 claims description 3
- 229960001221 pirarubicin Drugs 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 229960001052 streptozocin Drugs 0.000 claims description 3
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims description 3
- 230000007704 transition Effects 0.000 claims description 3
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 claims description 3
- 229950001353 tretamine Drugs 0.000 claims description 3
- 229960001055 uracil mustard Drugs 0.000 claims description 3
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-N 0.000 claims description 2
- 208000003200 Adenoma Diseases 0.000 claims description 2
- 208000004804 Adenomatous Polyps Diseases 0.000 claims description 2
- 208000006468 Adrenal Cortex Neoplasms Diseases 0.000 claims description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 2
- 229940122361 Bisphosphonate Drugs 0.000 claims description 2
- 208000007690 Brenner tumor Diseases 0.000 claims description 2
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 claims description 2
- 229930188224 Cryptophycin Natural products 0.000 claims description 2
- 108010002156 Depsipeptides Proteins 0.000 claims description 2
- AUGQEEXBDZWUJY-ZLJUKNTDSA-N Diacetoxyscirpenol Chemical compound C([C@]12[C@]3(C)[C@H](OC(C)=O)[C@@H](O)[C@H]1O[C@@H]1C=C(C)CC[C@@]13COC(=O)C)O2 AUGQEEXBDZWUJY-ZLJUKNTDSA-N 0.000 claims description 2
- 208000003098 Ganglion Cysts Diseases 0.000 claims description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
- 208000008999 Giant Cell Carcinoma Diseases 0.000 claims description 2
- 206010018691 Granuloma Diseases 0.000 claims description 2
- 208000002291 Histiocytic Sarcoma Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 102000017578 LAG3 Human genes 0.000 claims description 2
- 206010024305 Leukaemia monocytic Diseases 0.000 claims description 2
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 claims description 2
- 208000007369 Malignant Mixed Tumor Diseases 0.000 claims description 2
- 208000007054 Medullary Carcinoma Diseases 0.000 claims description 2
- 208000002030 Merkel cell carcinoma Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 2
- 241000232901 Nephroma Species 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- XOMRRQXKHMYMOC-UHFFFAOYSA-N O-palmitoylcarnitine Chemical compound CCCCCCCCCCCCCCCC(=O)OC(CC([O-])=O)C[N+](C)(C)C XOMRRQXKHMYMOC-UHFFFAOYSA-N 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000007871 Odontogenic Tumors Diseases 0.000 claims description 2
- 235000008331 Pinus X rigitaeda Nutrition 0.000 claims description 2
- 235000011613 Pinus brutia Nutrition 0.000 claims description 2
- 241000018646 Pinus brutia Species 0.000 claims description 2
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Porfiromycine Chemical compound O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 claims description 2
- 108091080027 Short-chain family Proteins 0.000 claims description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 2
- 208000005400 Synovial Cyst Diseases 0.000 claims description 2
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 claims description 2
- 201000002454 adrenal cortex cancer Diseases 0.000 claims description 2
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 claims description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229960003437 aminoglutethimide Drugs 0.000 claims description 2
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 claims description 2
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 claims description 2
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 claims description 2
- 201000007436 apocrine adenocarcinoma Diseases 0.000 claims description 2
- 150000001541 aziridines Chemical class 0.000 claims description 2
- 150000004663 bisphosphonates Chemical class 0.000 claims description 2
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 claims description 2
- 210000004252 chorionic villi Anatomy 0.000 claims description 2
- 208000009060 clear cell adenocarcinoma Diseases 0.000 claims description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 2
- 210000002919 epithelial cell Anatomy 0.000 claims description 2
- 230000001605 fetal effect Effects 0.000 claims description 2
- 201000008825 fibrosarcoma of bone Diseases 0.000 claims description 2
- 235000019152 folic acid Nutrition 0.000 claims description 2
- 239000011724 folic acid Substances 0.000 claims description 2
- 229960000304 folic acid Drugs 0.000 claims description 2
- 150000002224 folic acids Chemical class 0.000 claims description 2
- 230000003325 follicular Effects 0.000 claims description 2
- 201000003444 follicular lymphoma Diseases 0.000 claims description 2
- 230000000762 glandular Effects 0.000 claims description 2
- 210000004565 granule cell Anatomy 0.000 claims description 2
- 230000002440 hepatic effect Effects 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 claims description 2
- 201000010985 invasive ductal carcinoma Diseases 0.000 claims description 2
- 125000003473 lipid group Chemical group 0.000 claims description 2
- 229960003538 lonidamine Drugs 0.000 claims description 2
- WDRYRZXSPDWGEB-UHFFFAOYSA-N lonidamine Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl WDRYRZXSPDWGEB-UHFFFAOYSA-N 0.000 claims description 2
- 230000000527 lymphocytic effect Effects 0.000 claims description 2
- 208000025036 lymphosarcoma Diseases 0.000 claims description 2
- 230000036244 malformation Effects 0.000 claims description 2
- 201000007054 malignant Sertoli cell tumor Diseases 0.000 claims description 2
- 201000006812 malignant histiocytosis Diseases 0.000 claims description 2
- 208000021810 malignant mixed neoplasm Diseases 0.000 claims description 2
- 201000009020 malignant peripheral nerve sheath tumor Diseases 0.000 claims description 2
- 208000025854 malignant tumor of adrenal cortex Diseases 0.000 claims description 2
- 208000027202 mammary Paget disease Diseases 0.000 claims description 2
- 201000008749 mast-cell sarcoma Diseases 0.000 claims description 2
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims description 2
- 201000010225 mixed cell type cancer Diseases 0.000 claims description 2
- 208000029638 mixed neoplasm Diseases 0.000 claims description 2
- 201000006894 monocytic leukemia Diseases 0.000 claims description 2
- 201000010879 mucinous adenocarcinoma Diseases 0.000 claims description 2
- 208000025113 myeloid leukemia Diseases 0.000 claims description 2
- YBZRLMLGUBIIDN-DKOJYIQKSA-N n-[2-[[(2r,3r,4r,5s,6s)-2-[(1s)-1,2-dihydroxyethyl]-4,5-dihydroxy-6-(7h-purin-6-ylamino)oxan-3-yl]amino]-2-oxoethyl]-14-methylpentadecanamide Chemical compound O1[C@@H]([C@@H](O)CO)[C@H](NC(=O)CNC(=O)CCCCCCCCCCCCC(C)C)[C@@H](O)[C@H](O)[C@H]1NC1=NC=NC2=C1NC=N2 YBZRLMLGUBIIDN-DKOJYIQKSA-N 0.000 claims description 2
- 208000025351 nephroma Diseases 0.000 claims description 2
- 208000029974 neurofibrosarcoma Diseases 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 208000027825 odontogenic neoplasm Diseases 0.000 claims description 2
- 229950010773 pidilizumab Drugs 0.000 claims description 2
- 208000015768 polyposis Diseases 0.000 claims description 2
- 150000003212 purines Chemical class 0.000 claims description 2
- 230000002207 retinal effect Effects 0.000 claims description 2
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 claims description 2
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 claims description 2
- YBZRLMLGUBIIDN-UHFFFAOYSA-N spicamycin Natural products O1C(C(O)CO)C(NC(=O)CNC(=O)CCCCCCCCCCCCC(C)C)C(O)C(O)C1NC1=NC=NC2=C1NC=N2 YBZRLMLGUBIIDN-UHFFFAOYSA-N 0.000 claims description 2
- 239000013589 supplement Substances 0.000 claims description 2
- 206010042863 synovial sarcoma Diseases 0.000 claims description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 2
- 229960001278 teniposide Drugs 0.000 claims description 2
- 210000000115 thoracic cavity Anatomy 0.000 claims description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims description 2
- 208000029335 trabecular adenocarcinoma Diseases 0.000 claims description 2
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims 4
- 208000037828 epithelial carcinoma Diseases 0.000 claims 3
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 3
- 208000017708 myomatous neoplasm Diseases 0.000 claims 3
- 150000007513 acids Chemical class 0.000 claims 2
- QCXJFISCRQIYID-IAEPZHFASA-N 2-amino-1-n-[(3s,6s,7r,10s,16s)-3-[(2s)-butan-2-yl]-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-10-propan-2-yl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-4,6-dimethyl-3-oxo-9-n-[(3s,6s,7r,10s,16s)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propa Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N=C2C(C(=O)N[C@@H]3C(=O)N[C@H](C(N4CCC[C@H]4C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]3C)=O)[C@@H](C)CC)=C(N)C(=O)C(C)=C2O2)C2=C(C)C=C1 QCXJFISCRQIYID-IAEPZHFASA-N 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 206010014958 Eosinophilic leukaemia Diseases 0.000 claims 1
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 claims 1
- 101150030213 Lag3 gene Proteins 0.000 claims 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims 1
- 206010051696 Metastases to meninges Diseases 0.000 claims 1
- 208000003423 Mucocele Diseases 0.000 claims 1
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 claims 1
- 206010061332 Paraganglion neoplasm Diseases 0.000 claims 1
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 claims 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 claims 1
- 229930013930 alkaloid Natural products 0.000 claims 1
- 229940045713 antineoplastic alkylating drug ethylene imines Drugs 0.000 claims 1
- 208000019493 atypical carcinoid tumor Diseases 0.000 claims 1
- 210000004204 blood vessel Anatomy 0.000 claims 1
- 108700002839 cactinomycin Proteins 0.000 claims 1
- 229950009908 cactinomycin Drugs 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 239000012829 chemotherapy agent Substances 0.000 claims 1
- 208000021668 chronic eosinophilic leukemia Diseases 0.000 claims 1
- 208000002445 cystadenocarcinoma Diseases 0.000 claims 1
- 230000002538 fungal effect Effects 0.000 claims 1
- 208000029824 high grade glioma Diseases 0.000 claims 1
- 208000003747 lymphoid leukemia Diseases 0.000 claims 1
- 201000011614 malignant glioma Diseases 0.000 claims 1
- 208000010492 mucinous cystadenocarcinoma Diseases 0.000 claims 1
- 201000000050 myeloid neoplasm Diseases 0.000 claims 1
- 229940127075 other antimetabolite Drugs 0.000 claims 1
- 201000010198 papillary carcinoma Diseases 0.000 claims 1
- 201000010210 papillary cystadenocarcinoma Diseases 0.000 claims 1
- 208000024641 papillary serous cystadenocarcinoma Diseases 0.000 claims 1
- 208000007312 paraganglioma Diseases 0.000 claims 1
- 150000003230 pyrimidines Chemical class 0.000 claims 1
- 208000000649 small cell carcinoma Diseases 0.000 claims 1
- 208000010485 smooth muscle tumor Diseases 0.000 claims 1
- 238000009169 immunotherapy Methods 0.000 abstract description 42
- 150000001875 compounds Chemical class 0.000 abstract description 41
- 230000000694 effects Effects 0.000 abstract description 25
- 102000008203 CTLA-4 Antigen Human genes 0.000 abstract description 23
- 108010021064 CTLA-4 Antigen Proteins 0.000 abstract description 23
- 230000003278 mimic effect Effects 0.000 abstract description 19
- 230000028993 immune response Effects 0.000 abstract description 11
- 230000001093 anti-cancer Effects 0.000 abstract description 10
- 230000008685 targeting Effects 0.000 abstract description 9
- 230000006698 induction Effects 0.000 abstract description 8
- 229920000768 polyamine Polymers 0.000 abstract description 3
- 230000001681 protective effect Effects 0.000 abstract description 3
- 238000010586 diagram Methods 0.000 abstract description 2
- 238000010172 mouse model Methods 0.000 abstract description 2
- 230000004904 long-term response Effects 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 72
- 239000000523 sample Substances 0.000 description 51
- 210000001519 tissue Anatomy 0.000 description 49
- 210000001744 T-lymphocyte Anatomy 0.000 description 48
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 40
- 239000003814 drug Substances 0.000 description 36
- 229940079593 drug Drugs 0.000 description 34
- 108090000623 proteins and genes Proteins 0.000 description 33
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 30
- 210000003289 regulatory T cell Anatomy 0.000 description 28
- 230000004614 tumor growth Effects 0.000 description 28
- 230000008595 infiltration Effects 0.000 description 23
- 238000001764 infiltration Methods 0.000 description 23
- 102000004169 proteins and genes Human genes 0.000 description 23
- 230000004083 survival effect Effects 0.000 description 23
- 238000010186 staining Methods 0.000 description 21
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 19
- 239000002953 phosphate buffered saline Substances 0.000 description 19
- 235000003642 hunger Nutrition 0.000 description 16
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 15
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 15
- 230000037351 starvation Effects 0.000 description 15
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 14
- 238000002560 therapeutic procedure Methods 0.000 description 14
- 230000004900 autophagic degradation Effects 0.000 description 13
- 241000701806 Human papillomavirus Species 0.000 description 12
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 230000003993 interaction Effects 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 11
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 11
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 11
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 11
- 229960001138 acetylsalicylic acid Drugs 0.000 description 11
- 230000027455 binding Effects 0.000 description 11
- 238000009739 binding Methods 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- FSASIHFSFGAIJM-UHFFFAOYSA-N 3-methyladenine Chemical compound CN1C=NC(N)=C2N=CN=C12 FSASIHFSFGAIJM-UHFFFAOYSA-N 0.000 description 10
- 230000037449 immunogenic cell death Effects 0.000 description 10
- 229940090044 injection Drugs 0.000 description 10
- 239000003550 marker Substances 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 description 10
- 229960002110 vincristine sulfate Drugs 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 108010002350 Interleukin-2 Proteins 0.000 description 9
- 102000000588 Interleukin-2 Human genes 0.000 description 9
- 229940123237 Taxane Drugs 0.000 description 9
- 229940088598 enzyme Drugs 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- FPJGLSZLQLNZIW-VIFPVBQESA-N (2s)-2-amino-3-(4-methyl-1h-indol-3-yl)propanoic acid Chemical compound CC1=CC=CC2=C1C(C[C@H](N)C(O)=O)=CN2 FPJGLSZLQLNZIW-VIFPVBQESA-N 0.000 description 8
- 101000840545 Bacillus thuringiensis L-isoleucine-4-hydroxylase Proteins 0.000 description 8
- 206010006187 Breast cancer Diseases 0.000 description 8
- 208000026310 Breast neoplasm Diseases 0.000 description 8
- 229940124783 FAK inhibitor Drugs 0.000 description 8
- 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 8
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 8
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 8
- 102100022338 Integrin alpha-M Human genes 0.000 description 8
- 102000003814 Interleukin-10 Human genes 0.000 description 8
- 108090000174 Interleukin-10 Proteins 0.000 description 8
- 101001037255 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Indoleamine 2,3-dioxygenase Proteins 0.000 description 8
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 8
- KAOMOVYHGLSFHQ-UTOQUPLUSA-N anacardic acid Chemical compound CCC\C=C/C\C=C/CCCCCCCC1=CC=CC(O)=C1C(O)=O KAOMOVYHGLSFHQ-UTOQUPLUSA-N 0.000 description 8
- 235000014398 anacardic acid Nutrition 0.000 description 8
- ADFWQBGTDJIESE-UHFFFAOYSA-N anacardic acid 15:0 Natural products CCCCCCCCCCCCCCCC1=CC=CC(O)=C1C(O)=O ADFWQBGTDJIESE-UHFFFAOYSA-N 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 8
- 230000007812 deficiency Effects 0.000 description 8
- 238000003364 immunohistochemistry Methods 0.000 description 8
- 208000020816 lung neoplasm Diseases 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
- 102000016614 Autophagy-Related Protein 5 Human genes 0.000 description 7
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 7
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 7
- 108010050904 Interferons Proteins 0.000 description 7
- 102000014150 Interferons Human genes 0.000 description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 7
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 7
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 7
- 229940022663 acetate Drugs 0.000 description 7
- 229940045799 anthracyclines and related substance Drugs 0.000 description 7
- 229960004397 cyclophosphamide Drugs 0.000 description 7
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 7
- 210000004443 dendritic cell Anatomy 0.000 description 7
- 239000003651 drinking water Substances 0.000 description 7
- 235000020188 drinking water Nutrition 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 229940079322 interferon Drugs 0.000 description 7
- 201000005202 lung cancer Diseases 0.000 description 7
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 7
- 229940016667 resveratrol Drugs 0.000 description 7
- 235000021283 resveratrol Nutrition 0.000 description 7
- 229960004641 rituximab Drugs 0.000 description 7
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 7
- 108090000663 Annexin A1 Proteins 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 102100030708 GTPase KRas Human genes 0.000 description 6
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 6
- 102000013691 Interleukin-17 Human genes 0.000 description 6
- 108050003558 Interleukin-17 Proteins 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 102100031789 Myeloid-derived growth factor Human genes 0.000 description 6
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 6
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 6
- 230000000735 allogeneic effect Effects 0.000 description 6
- 238000002659 cell therapy Methods 0.000 description 6
- 229940120124 dichloroacetate Drugs 0.000 description 6
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 6
- 238000012423 maintenance Methods 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 229940068196 placebo Drugs 0.000 description 6
- 239000000902 placebo Substances 0.000 description 6
- 229960001285 quercetin Drugs 0.000 description 6
- 235000005875 quercetin Nutrition 0.000 description 6
- 238000001959 radiotherapy Methods 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- AWLWPSSHYJQPCH-VIFPVBQESA-N (2s)-2-amino-3-(6-nitro-1h-indol-3-yl)propanoic acid Chemical compound [O-][N+](=O)C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 AWLWPSSHYJQPCH-VIFPVBQESA-N 0.000 description 5
- ZADWXFSZEAPBJS-JTQLQIEISA-N 1-methyl-L-tryptophan Chemical compound C1=CC=C2N(C)C=C(C[C@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-JTQLQIEISA-N 0.000 description 5
- YTRNLFYTHYWDAU-KDOFPFPSSA-N 2-[(3s,5r)-5-[6-(2,4-dichlorophenyl)hexyl]-3-hydroxy-2-oxooxolan-3-yl]acetic acid Chemical compound O1C(=O)[C@](CC(=O)O)(O)C[C@H]1CCCCCCC1=CC=C(Cl)C=C1Cl YTRNLFYTHYWDAU-KDOFPFPSSA-N 0.000 description 5
- YIPRQTYMJYGRER-UHFFFAOYSA-N 3-aminonaphthalene-1-carboxylic acid Chemical compound C1=CC=CC2=CC(N)=CC(C(O)=O)=C21 YIPRQTYMJYGRER-UHFFFAOYSA-N 0.000 description 5
- BKAJNAXTPSGJCU-UHFFFAOYSA-N 4-methyl-2-oxopentanoic acid Chemical compound CC(C)CC(=O)C(O)=O BKAJNAXTPSGJCU-UHFFFAOYSA-N 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 5
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 5
- 102000004388 Interleukin-4 Human genes 0.000 description 5
- 108090000978 Interleukin-4 Proteins 0.000 description 5
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 206010070834 Sensitisation Diseases 0.000 description 5
- 108020002494 acetyltransferase Proteins 0.000 description 5
- 102000005421 acetyltransferase Human genes 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 239000000090 biomarker Substances 0.000 description 5
- 210000002798 bone marrow cell Anatomy 0.000 description 5
- 230000000973 chemotherapeutic effect Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- GLBDSPDDIJHXAQ-QULNWQEGSA-N hedamycin Chemical compound CC1OC1C1C(C=2OC3=C4C(=O)C5=C(O)C(O[C@@H]6O[C@H](C)[C@@H](O)[C@](C)(C6)N(C)C)=CC(O[C@H]6O[C@H](C)[C@@H](O)[C@@H](C6)N(C)C)=C5C(=O)C4=CC(C)=C3C(=O)C=2)(C)O1 GLBDSPDDIJHXAQ-QULNWQEGSA-N 0.000 description 5
- RZOFHOWMWMTHDX-UHFFFAOYSA-N hedamycin Natural products CC1OC1C1C(C=2OC3=C4C(=O)C5=C(O)C(C6OC(C)C(O)C(C)(C6)N(C)C)=CC(=C5C(=O)C4=CC(C)=C3C(=O)C=2)C2OC(C)C(O)C(C2)N(C)C)(C)O1 RZOFHOWMWMTHDX-UHFFFAOYSA-N 0.000 description 5
- 230000005746 immune checkpoint blockade Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- ZADWXFSZEAPBJS-UHFFFAOYSA-N racemic N-methyl tryptophan Natural products C1=CC=C2N(C)C=C(CC(N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-UHFFFAOYSA-N 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000008313 sensitization Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 229960004964 temozolomide Drugs 0.000 description 5
- 229960005486 vaccine Drugs 0.000 description 5
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 4
- XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 4
- GAUUPDQWKHTCAX-VIFPVBQESA-N (2s)-2-amino-3-(1-benzothiophen-3-yl)propanoic acid Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CSC2=C1 GAUUPDQWKHTCAX-VIFPVBQESA-N 0.000 description 4
- KZDNJQUJBMDHJW-VIFPVBQESA-N (2s)-2-amino-3-(5-bromo-1h-indol-3-yl)propanoic acid Chemical compound C1=C(Br)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 KZDNJQUJBMDHJW-VIFPVBQESA-N 0.000 description 4
- GDMRVYIFGPMUCG-JTQLQIEISA-N (2s)-2-azaniumyl-3-(6-methyl-1h-indol-3-yl)propanoate Chemical compound CC1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 GDMRVYIFGPMUCG-JTQLQIEISA-N 0.000 description 4
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical group OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 4
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 4
- KVNPSKDDJARYKK-JTQLQIEISA-N 5-methoxytryptophan Chemical compound COC1=CC=C2NC=C(C[C@H](N)C(O)=O)C2=C1 KVNPSKDDJARYKK-JTQLQIEISA-N 0.000 description 4
- XHLKOHSAWQPOFO-UHFFFAOYSA-N 5-phenyl-1h-imidazole Chemical compound N1C=NC=C1C1=CC=CC=C1 XHLKOHSAWQPOFO-UHFFFAOYSA-N 0.000 description 4
- YMEXGEAJNZRQEH-UHFFFAOYSA-N 6-Fluoro-DL-tryptophan Chemical compound FC1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 YMEXGEAJNZRQEH-UHFFFAOYSA-N 0.000 description 4
- ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 4
- 101150102163 ATG7 gene Proteins 0.000 description 4
- 102000004145 Annexin A1 Human genes 0.000 description 4
- 206010061692 Benign muscle neoplasm Diseases 0.000 description 4
- 229930184584 Ditrisarubicin Natural products 0.000 description 4
- 108010074604 Epoetin Alfa Proteins 0.000 description 4
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 4
- 208000032612 Glial tumor Diseases 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 102100036705 Interleukin-23 subunit alpha Human genes 0.000 description 4
- 108010066979 Interleukin-27 Proteins 0.000 description 4
- 206010069755 K-ras gene mutation Diseases 0.000 description 4
- 108010000817 Leuprolide Proteins 0.000 description 4
- 201000004458 Myoma Diseases 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 206010057249 Phagocytosis Diseases 0.000 description 4
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 4
- VSWDORGPIHIGNW-UHFFFAOYSA-N Pyrrolidine dithiocarbamic acid Chemical compound SC(=S)N1CCCC1 VSWDORGPIHIGNW-UHFFFAOYSA-N 0.000 description 4
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 101150096483 atg5 gene Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- UJMDYLWCYJJYMO-UHFFFAOYSA-N benzene-1,2,3-tricarboxylic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1C(O)=O UJMDYLWCYJJYMO-UHFFFAOYSA-N 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 4
- 238000002648 combination therapy Methods 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 4
- 229940063519 doxorubicin hydrochloride liposome Drugs 0.000 description 4
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 4
- 229940030275 epigallocatechin gallate Drugs 0.000 description 4
- 238000013401 experimental design Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 239000002955 immunomodulating agent Substances 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 229960004338 leuprorelin Drugs 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 229940049920 malate Drugs 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 4
- 229960003539 mitoguazone Drugs 0.000 description 4
- MXWHMTNPTTVWDM-NXOFHUPFSA-N mitoguazone Chemical compound NC(N)=N\N=C(/C)\C=N\N=C(N)N MXWHMTNPTTVWDM-NXOFHUPFSA-N 0.000 description 4
- 229960000951 mycophenolic acid Drugs 0.000 description 4
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 4
- RCHQNUQAHJNRBY-UHFFFAOYSA-N n-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)NC)=CC=C1NC1=NC=C(C(F)(F)F)C(NCC=2C(=NC=CN=2)N(C)S(C)(=O)=O)=N1 RCHQNUQAHJNRBY-UHFFFAOYSA-N 0.000 description 4
- KKFHAJHLJHVUDM-UHFFFAOYSA-N n-vinylcarbazole Chemical compound C1=CC=C2N(C=C)C3=CC=CC=C3C2=C1 KKFHAJHLJHVUDM-UHFFFAOYSA-N 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 238000011275 oncology therapy Methods 0.000 description 4
- 238000001543 one-way ANOVA Methods 0.000 description 4
- 210000003463 organelle Anatomy 0.000 description 4
- 229960001972 panitumumab Drugs 0.000 description 4
- 230000008782 phagocytosis Effects 0.000 description 4
- 239000012660 pharmacological inhibitor Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- IASPBORHOMBZMY-UHFFFAOYSA-N srt1720 Chemical compound C=1N=C2C=CC=CC2=NC=1C(=O)NC1=CC=CC=C1C(N=C1SC=2)=CN1C=2CN1CCNCC1 IASPBORHOMBZMY-UHFFFAOYSA-N 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- IIQKYWMOMQWBER-VIFPVBQESA-N (2s)-2-amino-3-(1-benzofuran-3-yl)propanoic acid Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=COC2=C1 IIQKYWMOMQWBER-VIFPVBQESA-N 0.000 description 3
- XDHNQDDQEHDUTM-XJKSCTEHSA-N (3z,5e,7r,8s,9r,11e,13e,15s,16r)-16-[(2s,3r,4s)-4-[(2r,4r,5s,6r)-2,4-dihydroxy-5-methyl-6-propan-2-yloxan-2-yl]-3-hydroxypentan-2-yl]-8-hydroxy-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraen-2-one Chemical compound CO[C@H]1\C=C\C=C(C)\C[C@@H](C)[C@H](O)[C@H](C)\C=C(/C)\C=C(OC)\C(=O)O[C@@H]1[C@@H](C)[C@@H](O)[C@H](C)[C@]1(O)O[C@H](C(C)C)[C@@H](C)[C@H](O)C1 XDHNQDDQEHDUTM-XJKSCTEHSA-N 0.000 description 3
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 3
- QSHLMQDRPXXYEE-ZETCQYMHSA-N 4-hydroxy-L-tryptophan Chemical compound C1=CC(O)=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QSHLMQDRPXXYEE-ZETCQYMHSA-N 0.000 description 3
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 3
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 3
- 108010092776 Autophagy-Related Protein 5 Proteins 0.000 description 3
- 108010092778 Autophagy-Related Protein 7 Proteins 0.000 description 3
- VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 3
- 238000011357 CAR T-cell therapy Methods 0.000 description 3
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- VFZRZRDOXPRTSC-UHFFFAOYSA-N DMBA Natural products COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 3
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 3
- 108010029961 Filgrastim Proteins 0.000 description 3
- OVSQVDMCBVZWGM-IDRAQACASA-N Hirsutrin Natural products O([C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1)C1=C(c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O OVSQVDMCBVZWGM-IDRAQACASA-N 0.000 description 3
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 3
- 101000818522 Homo sapiens fMet-Leu-Phe receptor Proteins 0.000 description 3
- FVQOMEDMFUMIMO-UHFFFAOYSA-N Hyperosid Natural products OC1C(O)C(O)C(CO)OC1OC1C(=O)C2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 FVQOMEDMFUMIMO-UHFFFAOYSA-N 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 102100022297 Integrin alpha-X Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 102100030703 Interleukin-22 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 3
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 3
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 3
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 3
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 3
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 3
- 240000007594 Oryza sativa Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- 108010016731 PPAR gamma Proteins 0.000 description 3
- CZYWHNTUXNGDGR-UHFFFAOYSA-L Pamidronate disodium Chemical compound O.O.O.O.O.[Na+].[Na+].NCCC(O)(P(O)([O-])=O)P(O)([O-])=O CZYWHNTUXNGDGR-UHFFFAOYSA-L 0.000 description 3
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101100215487 Sus scrofa ADRA2A gene Proteins 0.000 description 3
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 3
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 3
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 3
- 102100022979 Ubiquitin-like modifier-activating enzyme ATG7 Human genes 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 3
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 3
- 229960003852 atezolizumab Drugs 0.000 description 3
- XDHNQDDQEHDUTM-UHFFFAOYSA-N bafliomycin A1 Natural products COC1C=CC=C(C)CC(C)C(O)C(C)C=C(C)C=C(OC)C(=O)OC1C(C)C(O)C(C)C1(O)OC(C(C)C)C(C)C(O)C1 XDHNQDDQEHDUTM-UHFFFAOYSA-N 0.000 description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 229940022399 cancer vaccine Drugs 0.000 description 3
- 238000009566 cancer vaccine Methods 0.000 description 3
- 229960005395 cetuximab Drugs 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000006196 deacetylation Effects 0.000 description 3
- 238000003381 deacetylation reaction Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 3
- BIFMNMPSIYHKDN-FJXQXJEOSA-N dexrazoxane hydrochloride Chemical compound [H+].[Cl-].C([C@H](C)N1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1 BIFMNMPSIYHKDN-FJXQXJEOSA-N 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 3
- QXRSDHAAWVKZLJ-TYFQHMATSA-N epothilone b Chemical compound C/C([C@@H]1C[C@@H]2O[C@@]2(C)CCC[C@@H]([C@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-TYFQHMATSA-N 0.000 description 3
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 3
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
- 229910052732 germanium Inorganic materials 0.000 description 3
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 3
- 229960002442 glucosamine Drugs 0.000 description 3
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 3
- 229960003727 granisetron Drugs 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- OVSQVDMCBVZWGM-QCKGUQPXSA-N isoquercetin Natural products OC[C@@H]1O[C@@H](OC2=C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)c(O)c4)[C@H](O)[C@@H](O)[C@@H]1O OVSQVDMCBVZWGM-QCKGUQPXSA-N 0.000 description 3
- MBOMYENWWXQSNW-AWEZNQCLSA-N ixazomib citrate Chemical compound N([C@@H](CC(C)C)B1OC(CC(O)=O)(CC(O)=O)C(=O)O1)C(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MBOMYENWWXQSNW-AWEZNQCLSA-N 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 3
- 229960000350 mitotane Drugs 0.000 description 3
- 229950006780 n-acetylglucosamine Drugs 0.000 description 3
- 210000000581 natural killer T-cell Anatomy 0.000 description 3
- WAXQNWCZJDTGBU-UHFFFAOYSA-N netupitant Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WAXQNWCZJDTGBU-UHFFFAOYSA-N 0.000 description 3
- 229960005163 netupitant Drugs 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229960003278 osimertinib Drugs 0.000 description 3
- DUYJMQONPNNFPI-UHFFFAOYSA-N osimertinib Chemical compound COC1=CC(N(C)CCN(C)C)=C(NC(=O)C=C)C=C1NC1=NC=CC(C=2C3=CC=CC=C3N(C)C=2)=N1 DUYJMQONPNNFPI-UHFFFAOYSA-N 0.000 description 3
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 102000007863 pattern recognition receptors Human genes 0.000 description 3
- 108010089193 pattern recognition receptors Proteins 0.000 description 3
- 229950007460 patupilone Drugs 0.000 description 3
- MQHIQUBXFFAOMK-UHFFFAOYSA-N pazopanib hydrochloride Chemical compound Cl.C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 MQHIQUBXFFAOMK-UHFFFAOYSA-N 0.000 description 3
- 108010001564 pegaspargase Proteins 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000010837 poor prognosis Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- OVSQVDMCBVZWGM-QSOFNFLRSA-N quercetin 3-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-QSOFNFLRSA-N 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- 229960001860 salicylate Drugs 0.000 description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 230000001235 sensitizing effect Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229940031351 tetravalent vaccine Drugs 0.000 description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 3
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 3
- 229960003862 vemurafenib Drugs 0.000 description 3
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 description 3
- 229960000237 vorinostat Drugs 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- MNULEGDCPYONBU-DJRUDOHVSA-N (1s,4r,5z,5'r,6'r,7e,10s,11r,12s,14r,15s,18r,19r,20s,21e,26r,27s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@H]1CC[C@H](\C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)C(C)C(=O)[C@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)OC([C@H]2C)C1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-DJRUDOHVSA-N 0.000 description 2
- PXHANKVTFWSDSG-QLOBERJESA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 PXHANKVTFWSDSG-QLOBERJESA-N 0.000 description 2
- IFGIYSGOEZJNBE-LHJYHSJWSA-N (3s,4r,4as,7ar,12bs)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-3-ium-7-one;bromide Chemical compound [Br-].C([N@@+]1(C)[C@@H]2CC=3C4=C(C(=CC=3)O)O[C@@H]3[C@]4([C@@]2(O)CCC3=O)CC1)C1CC1 IFGIYSGOEZJNBE-LHJYHSJWSA-N 0.000 description 2
- JXVAMODRWBNUSF-KZQKBALLSA-N (7s,9r,10r)-7-[(2r,4s,5s,6s)-5-[[(2s,4as,5as,7s,9s,9ar,10ar)-2,9-dimethyl-3-oxo-4,4a,5a,6,7,9,9a,10a-octahydrodipyrano[4,2-a:4',3'-e][1,4]dioxin-7-yl]oxy]-4-(dimethylamino)-6-methyloxan-2-yl]oxy-10-[(2s,4s,5s,6s)-4-(dimethylamino)-5-hydroxy-6-methyloxan-2 Chemical compound O([C@@H]1C2=C(O)C=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C2[C@@H](O[C@@H]2O[C@@H](C)[C@@H](O[C@@H]3O[C@@H](C)[C@H]4O[C@@H]5O[C@@H](C)C(=O)C[C@@H]5O[C@H]4C3)[C@H](C2)N(C)C)C[C@]1(O)CC)[C@H]1C[C@H](N(C)C)[C@H](O)[C@H](C)O1 JXVAMODRWBNUSF-KZQKBALLSA-N 0.000 description 2
- MWWSFMDVAYGXBV-FGBSZODSSA-N (7s,9s)-7-[(2r,4s,5r,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydron;chloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-FGBSZODSSA-N 0.000 description 2
- BIZNHCWFGNKBBZ-JLHYYAGUSA-N (e)-2-cyano-3-(1-phenylindol-3-yl)prop-2-enoic acid Chemical compound C12=CC=CC=C2C(/C=C(C(=O)O)\C#N)=CN1C1=CC=CC=C1 BIZNHCWFGNKBBZ-JLHYYAGUSA-N 0.000 description 2
- UJOUWHLYTQFUCU-WXXKFALUSA-N (e)-but-2-enedioic acid;6-ethyl-3-[3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-(oxan-4-ylamino)pyrazine-2-carboxamide Chemical compound OC(=O)\C=C\C(O)=O.N1=C(NC2CCOCC2)C(CC)=NC(C(N)=O)=C1NC(C=C1OC)=CC=C1N(CC1)CCC1N1CCN(C)CC1.N1=C(NC2CCOCC2)C(CC)=NC(C(N)=O)=C1NC(C=C1OC)=CC=C1N(CC1)CCC1N1CCN(C)CC1 UJOUWHLYTQFUCU-WXXKFALUSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- VXZCUHNJXSIJIM-MEBGWEOYSA-N (z)-but-2-enedioic acid;(e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound OC(=O)\C=C/C(O)=O.C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 VXZCUHNJXSIJIM-MEBGWEOYSA-N 0.000 description 2
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- LWRSYTXEQUUTKW-UHFFFAOYSA-N 2,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1 LWRSYTXEQUUTKW-UHFFFAOYSA-N 0.000 description 2
- QXLQZLBNPTZMRK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-(2,4-dimethylphenyl)prop-2-en-1-one Chemical compound CN(C)CC(=C)C(=O)C1=CC=C(C)C=C1C QXLQZLBNPTZMRK-UHFFFAOYSA-N 0.000 description 2
- BVAHPPKGOOJSPU-UHFFFAOYSA-N 2-[[5-chloro-2-[(5-methyl-2-propan-2-ylpyrazol-3-yl)amino]pyridin-4-yl]amino]-n-methoxybenzamide Chemical compound CONC(=O)C1=CC=CC=C1NC1=CC(NC=2N(N=C(C)C=2)C(C)C)=NC=C1Cl BVAHPPKGOOJSPU-UHFFFAOYSA-N 0.000 description 2
- VFTRKSBEFQDZKX-UHFFFAOYSA-N 3,3'-diindolylmethane Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4NC=3)=CNC2=C1 VFTRKSBEFQDZKX-UHFFFAOYSA-N 0.000 description 2
- SIIPNDKXZOTLEA-UHFFFAOYSA-N 3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide Chemical compound COC1=CC=C(C=2C=CC=CC=2)C=C1NS(=O)(=O)C1=CC(Cl)=CC(Cl)=C1O SIIPNDKXZOTLEA-UHFFFAOYSA-N 0.000 description 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 2
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 description 2
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 2
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
- RSHUYHGFYNFGRW-UHFFFAOYSA-N 7-sulfanylpurine Chemical compound C1=NC=C2N(S)C=NC2=N1 RSHUYHGFYNFGRW-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 241000024188 Andala Species 0.000 description 2
- 102100040006 Annexin A1 Human genes 0.000 description 2
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 2
- 108010024976 Asparaginase Proteins 0.000 description 2
- 102000015790 Asparaginase Human genes 0.000 description 2
- 229940123944 B7-H3 antagonist Drugs 0.000 description 2
- 102000004082 Calreticulin Human genes 0.000 description 2
- 108090000549 Calreticulin Proteins 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 208000005243 Chondrosarcoma Diseases 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 102100032218 Cytokine-inducible SH2-containing protein Human genes 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000588700 Dickeya chrysanthemi Species 0.000 description 2
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 2
- CITFYDYEWQIEPX-UHFFFAOYSA-N Flavanol Natural products O1C2=CC(OCC=C(C)C)=CC(O)=C2C(=O)C(O)C1C1=CC=C(O)C=C1 CITFYDYEWQIEPX-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 102100031351 Galectin-9 Human genes 0.000 description 2
- 101710121810 Galectin-9 Proteins 0.000 description 2
- ZWPRRQZNBDYKLH-VIFPVBQESA-N Gemigliptin Chemical compound C([C@@H](N)CC(=O)N1CC2=C(C(=NC(=N2)C(F)(F)F)C(F)(F)F)CC1)N1CC(F)(F)CCC1=O ZWPRRQZNBDYKLH-VIFPVBQESA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000943420 Homo sapiens Cytokine-inducible SH2-containing protein Proteins 0.000 description 2
- 101001002470 Homo sapiens Interferon lambda-1 Proteins 0.000 description 2
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 description 2
- 101000853000 Homo sapiens Interleukin-26 Proteins 0.000 description 2
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 description 2
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 108010003272 Hyaluronate lyase Proteins 0.000 description 2
- 102000001974 Hyaluronidases Human genes 0.000 description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010079944 Interferon-alpha2b Proteins 0.000 description 2
- 108090000177 Interleukin-11 Proteins 0.000 description 2
- 102000003815 Interleukin-11 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 108090000172 Interleukin-15 Proteins 0.000 description 2
- 102000003812 Interleukin-15 Human genes 0.000 description 2
- 101800003050 Interleukin-16 Proteins 0.000 description 2
- 102000049772 Interleukin-16 Human genes 0.000 description 2
- 102100033101 Interleukin-17B Human genes 0.000 description 2
- 102000003810 Interleukin-18 Human genes 0.000 description 2
- 108090000171 Interleukin-18 Proteins 0.000 description 2
- 102100039879 Interleukin-19 Human genes 0.000 description 2
- 108050009288 Interleukin-19 Proteins 0.000 description 2
- 108010065637 Interleukin-23 Proteins 0.000 description 2
- 102100036678 Interleukin-27 subunit alpha Human genes 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 108010002335 Interleukin-9 Proteins 0.000 description 2
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 2
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 229910052765 Lutetium Inorganic materials 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- VJRAUFKOOPNFIQ-UHFFFAOYSA-N Marcellomycin Natural products C12=C(O)C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C=C2C(C(=O)OC)C(CC)(O)CC1OC(OC1C)CC(N(C)C)C1OC(OC1C)CC(O)C1OC1CC(O)C(O)C(C)O1 VJRAUFKOOPNFIQ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 241000202349 Taxus brevifolia Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- OUUYBRCCFUEMLH-YDALLXLXSA-N [(1s)-2-[4-[bis(2-chloroethyl)amino]phenyl]-1-carboxyethyl]azanium;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 OUUYBRCCFUEMLH-YDALLXLXSA-N 0.000 description 2
- JNWFIPVDEINBAI-UHFFFAOYSA-N [5-hydroxy-4-[4-(1-methylindol-5-yl)-5-oxo-1H-1,2,4-triazol-3-yl]-2-propan-2-ylphenyl] dihydrogen phosphate Chemical compound C1=C(OP(O)(O)=O)C(C(C)C)=CC(C=2N(C(=O)NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O JNWFIPVDEINBAI-UHFFFAOYSA-N 0.000 description 2
- 238000002679 ablation Methods 0.000 description 2
- FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 description 2
- 229960004892 acemetacin Drugs 0.000 description 2
- 229940100228 acetyl coenzyme a Drugs 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- USNRYVNRPYXCSP-JUGPPOIOSA-N afatinib dimaleate Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 USNRYVNRPYXCSP-JUGPPOIOSA-N 0.000 description 2
- 229960002736 afatinib dimaleate Drugs 0.000 description 2
- 229960000548 alemtuzumab Drugs 0.000 description 2
- 229940098174 alkeran Drugs 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229960004909 aminosalicylic acid Drugs 0.000 description 2
- 229960002932 anastrozole Drugs 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000005809 anti-tumor immunity Effects 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 229960003272 asparaginase Drugs 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 2
- IPOKCKJONYRRHP-FMQUCBEESA-N balsalazide Chemical compound C1=CC(C(=O)NCCC(=O)O)=CC=C1\N=N\C1=CC=C(O)C(C(O)=O)=C1 IPOKCKJONYRRHP-FMQUCBEESA-N 0.000 description 2
- 229960004168 balsalazide Drugs 0.000 description 2
- 229960003094 belinostat Drugs 0.000 description 2
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 description 2
- MMIMIFULGMZVPO-UHFFFAOYSA-N benzyl 3-bromo-2,6-dinitro-5-phenylmethoxybenzoate Chemical compound [O-][N+](=O)C1=C(C(=O)OCC=2C=CC=CC=2)C([N+](=O)[O-])=C(Br)C=C1OCC1=CC=CC=C1 MMIMIFULGMZVPO-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 description 2
- 229950003054 binimetinib Drugs 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 229940031416 bivalent vaccine Drugs 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 description 2
- 229960001573 cabazitaxel Drugs 0.000 description 2
- 235000008207 calcium folinate Nutrition 0.000 description 2
- 239000011687 calcium folinate Substances 0.000 description 2
- KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000011278 co-treatment Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229960005061 crizotinib Drugs 0.000 description 2
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- BFSMGDJOXZAERB-UHFFFAOYSA-N dabrafenib Chemical compound S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 BFSMGDJOXZAERB-UHFFFAOYSA-N 0.000 description 2
- 229960002448 dasatinib Drugs 0.000 description 2
- 229940076705 defibrotide sodium Drugs 0.000 description 2
- 229960001251 denosumab Drugs 0.000 description 2
- 229960004102 dexrazoxane hydrochloride Drugs 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 229960004497 dinutuximab Drugs 0.000 description 2
- NYDXNILOWQXUOF-UHFFFAOYSA-L disodium;2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate Chemical compound [Na+].[Na+].C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)NC(CCC([O-])=O)C([O-])=O)C=C1 NYDXNILOWQXUOF-UHFFFAOYSA-L 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 229950006700 edatrexate Drugs 0.000 description 2
- FSIRXIHZBIXHKT-MHTVFEQDSA-N edatrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CC(CC)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FSIRXIHZBIXHKT-MHTVFEQDSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229950001969 encorafenib Drugs 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- JOZGNYDSEBIJDH-UHFFFAOYSA-N eniluracil Chemical compound O=C1NC=C(C#C)C(=O)N1 JOZGNYDSEBIJDH-UHFFFAOYSA-N 0.000 description 2
- 229950010213 eniluracil Drugs 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 229960003265 epirubicin hydrochloride Drugs 0.000 description 2
- 229960003388 epoetin alfa Drugs 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 229960000752 etoposide phosphate Drugs 0.000 description 2
- 229960005167 everolimus Drugs 0.000 description 2
- 229960004177 filgrastim Drugs 0.000 description 2
- XHEFDIBZLJXQHF-UHFFFAOYSA-N fisetin Chemical compound C=1C(O)=CC=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 XHEFDIBZLJXQHF-UHFFFAOYSA-N 0.000 description 2
- 150000002206 flavan-3-ols Chemical class 0.000 description 2
- 235000011987 flavanols Nutrition 0.000 description 2
- 229940081995 fluorouracil injection Drugs 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 229960002584 gefitinib Drugs 0.000 description 2
- 229960005144 gemcitabine hydrochloride Drugs 0.000 description 2
- 229960002458 gemigliptin Drugs 0.000 description 2
- 229960004859 glucarpidase Drugs 0.000 description 2
- 108010049491 glucarpidase Proteins 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 230000001744 histochemical effect Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229960002773 hyaluronidase Drugs 0.000 description 2
- 229960001507 ibrutinib Drugs 0.000 description 2
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 description 2
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 2
- 238000013394 immunophenotyping Methods 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 108090000681 interleukin 20 Proteins 0.000 description 2
- 108010074109 interleukin-22 Proteins 0.000 description 2
- 108090000237 interleukin-24 Proteins 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 229960000779 irinotecan hydrochloride Drugs 0.000 description 2
- 229940048117 irinotecan hydrochloride liposome Drugs 0.000 description 2
- 229960002951 ixazomib citrate Drugs 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229960001320 lapatinib ditosylate Drugs 0.000 description 2
- 229960002293 leucovorin calcium Drugs 0.000 description 2
- CMJCXYNUCSMDBY-ZDUSSCGKSA-N lgx818 Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=C(Cl)C=2)F)=N1 CMJCXYNUCSMDBY-ZDUSSCGKSA-N 0.000 description 2
- 229960002397 linagliptin Drugs 0.000 description 2
- 229960002247 lomustine Drugs 0.000 description 2
- IIXWYSCJSQVBQM-LLVKDONJSA-N lorlatinib Chemical compound N=1N(C)C(C#N)=C2C=1CN(C)C(=O)C1=CC=C(F)C=C1[C@@H](C)OC1=CC2=CN=C1N IIXWYSCJSQVBQM-LLVKDONJSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- OHSVLFRHMCKCQY-UHFFFAOYSA-N lutetium atom Chemical compound [Lu] OHSVLFRHMCKCQY-UHFFFAOYSA-N 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- 229960002514 melphalan hydrochloride Drugs 0.000 description 2
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 2
- 229960004963 mesalazine Drugs 0.000 description 2
- 229960004635 mesna Drugs 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 229960003105 metformin Drugs 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- VJRAUFKOOPNFIQ-TVEKBUMESA-N methyl (1r,2r,4s)-4-[(2r,4s,5s,6s)-5-[(2s,4s,5s,6s)-5-[(2s,4s,5s,6s)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-(dimethylamino)-6-methyloxan-2-yl]oxy-2-ethyl-2,5,7,10-tetrahydroxy-6,11-dioxo-3,4-dihydro-1h-tetracene-1-carboxylat Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1C[C@H](O)[C@H](O)[C@H](C)O1 VJRAUFKOOPNFIQ-TVEKBUMESA-N 0.000 description 2
- 229960002834 methylnaltrexone bromide Drugs 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- AZBFJBJXUQUQLF-UHFFFAOYSA-N n-(1,5-dimethylpyrrolidin-3-yl)pyrrolidine-1-carboxamide Chemical compound C1N(C)C(C)CC1NC(=O)N1CCCC1 AZBFJBJXUQUQLF-UHFFFAOYSA-N 0.000 description 2
- 229960000513 necitumumab Drugs 0.000 description 2
- 229950008835 neratinib Drugs 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229950008516 olaratumab Drugs 0.000 description 2
- 229930191479 oligomycin Natural products 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 229950007318 ozogamicin Drugs 0.000 description 2
- 229960003978 pamidronic acid Drugs 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229960005492 pazopanib hydrochloride Drugs 0.000 description 2
- HQQSBEDKMRHYME-UHFFFAOYSA-N pefloxacin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 HQQSBEDKMRHYME-UHFFFAOYSA-N 0.000 description 2
- 229960001744 pegaspargase Drugs 0.000 description 2
- 229960001373 pegfilgrastim Drugs 0.000 description 2
- 108010044644 pegfilgrastim Proteins 0.000 description 2
- 229960003349 pemetrexed disodium Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 229960001586 procarbazine hydrochloride Drugs 0.000 description 2
- 239000000186 progesterone Substances 0.000 description 2
- 229960003387 progesterone Drugs 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 229960004604 propranolol hydrochloride Drugs 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol hydrochloride Natural products C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- RWRDJVNMSZYMDV-UHFFFAOYSA-L radium chloride Chemical compound [Cl-].[Cl-].[Ra+2] RWRDJVNMSZYMDV-UHFFFAOYSA-L 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 108700042226 ras Genes Proteins 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229950004892 rodorubicin Drugs 0.000 description 2
- 229960004586 rosiglitazone Drugs 0.000 description 2
- HNMATTJJEPZZMM-BPKVFSPJSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-6-[[(2s,5z,9r,13e)-13-[2-[[4-[(2e)-2-[1-[4-(4-amino-4-oxobutoxy)phenyl]ethylidene]hydrazinyl]-2-methyl-4-oxobutan-2-yl]disulfanyl]ethylidene]-9-hydroxy-12-(m Chemical compound C1[C@H](OC)[C@@H](N(CC)C(C)=O)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSC(C)(C)CC(=O)N\N=C(/C)C=3C=CC(OCCCC(N)=O)=CC=3)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HNMATTJJEPZZMM-BPKVFSPJSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 2
- 229960004937 saxagliptin Drugs 0.000 description 2
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 2
- 108010033693 saxagliptin Proteins 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 229960004034 sitagliptin Drugs 0.000 description 2
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- VZZJRYRQSPEMTK-CALCHBBNSA-N sonidegib Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(N=C1)=CC=C1NC(=O)C1=CC=CC(C=2C=CC(OC(F)(F)F)=CC=2)=C1C VZZJRYRQSPEMTK-CALCHBBNSA-N 0.000 description 2
- IVDHYUQIDRJSTI-UHFFFAOYSA-N sorafenib tosylate Chemical compound [H+].CC1=CC=C(S([O-])(=O)=O)C=C1.C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 IVDHYUQIDRJSTI-UHFFFAOYSA-N 0.000 description 2
- ICXJVZHDZFXYQC-UHFFFAOYSA-N spongistatin 1 Natural products OC1C(O2)(O)CC(O)C(C)C2CCCC=CC(O2)CC(O)CC2(O2)CC(OC)CC2CC(=O)C(C)C(OC(C)=O)C(C)C(=C)CC(O2)CC(C)(O)CC2(O2)CC(OC(C)=O)CC2CC(=O)OC2C(O)C(CC(=C)CC(O)C=CC(Cl)=C)OC1C2C ICXJVZHDZFXYQC-UHFFFAOYSA-N 0.000 description 2
- 238000007447 staining method Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 2
- 229940021747 therapeutic vaccine Drugs 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- YFTWHEBLORWGNI-UHFFFAOYSA-N tiamiprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC(N)=NC2=C1NC=N2 YFTWHEBLORWGNI-UHFFFAOYSA-N 0.000 description 2
- 229960001740 tipiracil hydrochloride Drugs 0.000 description 2
- KGHYQYACJRXCAT-UHFFFAOYSA-N tipiracil hydrochloride Chemical compound Cl.N1C(=O)NC(=O)C(Cl)=C1CN1C(=N)CCC1 KGHYQYACJRXCAT-UHFFFAOYSA-N 0.000 description 2
- 229950007137 tisagenlecleucel Drugs 0.000 description 2
- 108010078373 tisagenlecleucel Proteins 0.000 description 2
- 229960002190 topotecan hydrochloride Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 230000002476 tumorcidal effect Effects 0.000 description 2
- 229960005088 urethane Drugs 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 1
- URLVCROWVOSNPT-XOTOMLERSA-N (2s)-4-[(13r)-13-hydroxy-13-[(2r,5r)-5-[(2r,5r)-5-[(1r)-1-hydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2h-furan-5-one Chemical compound O1[C@@H]([C@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCCCCC=2C(O[C@@H](C)C=2)=O)CC1 URLVCROWVOSNPT-XOTOMLERSA-N 0.000 description 1
- NAALWFYYHHJEFQ-ZASNTINBSA-N (2s,5r,6r)-6-[[(2r)-2-[[6-[4-[bis(2-hydroxyethyl)sulfamoyl]phenyl]-2-oxo-1h-pyridine-3-carbonyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC(O)=CC=1)C(=O)C(C(N1)=O)=CC=C1C1=CC=C(S(=O)(=O)N(CCO)CCO)C=C1 NAALWFYYHHJEFQ-ZASNTINBSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FONKWHRXTPJODV-DNQXCXABSA-N 1,3-bis[2-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydro-3h-pyrrolo[3,2-e]indole-6-carbonyl]-1h-indol-5-yl]urea Chemical compound C1([C@H](CCl)CN2C(=O)C=3NC4=CC=C(C=C4C=3)NC(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C4=CC(O)=C5NC=C(C5=C4[C@H](CCl)C3)C)=C2C=C(O)C2=C1C(C)=CN2 FONKWHRXTPJODV-DNQXCXABSA-N 0.000 description 1
- PZSFTBARUSGJTA-UHFFFAOYSA-N 1-n-(4-aminobutyl)butane-1,3-diamine Chemical compound CC(N)CCNCCCCN PZSFTBARUSGJTA-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- AYRABHFHMLXKBT-UHFFFAOYSA-N 2,6-Dimethyl-anthracen Natural products C1=C(C)C=CC2=CC3=CC(C)=CC=C3C=C21 AYRABHFHMLXKBT-UHFFFAOYSA-N 0.000 description 1
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
- OUUYBRCCFUEMLH-UHFFFAOYSA-N 2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoic acid;hydrochloride Chemical compound [Cl-].OC(=O)C([NH3+])CC1=CC=C(N(CCCl)CCCl)C=C1 OUUYBRCCFUEMLH-UHFFFAOYSA-N 0.000 description 1
- FDAYLTPAFBGXAB-UHFFFAOYSA-N 2-chloro-n,n-bis(2-chloroethyl)ethanamine Chemical compound ClCCN(CCCl)CCCl FDAYLTPAFBGXAB-UHFFFAOYSA-N 0.000 description 1
- BIZNHCWFGNKBBZ-UHFFFAOYSA-N 2-cyano-3-(1-phenylindol-3-yl)prop-2-enoic acid Chemical compound C12=CC=CC=C2C(C=C(C(=O)O)C#N)=CN1C1=CC=CC=C1 BIZNHCWFGNKBBZ-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 229940093768 3,3'-diindolylmethane Drugs 0.000 description 1
- 235000010045 3,3'-diindolylmethane Nutrition 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- YCBPQSYLYYBPDW-UHFFFAOYSA-N 4-methyl-n-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide;hydrate;hydrochloride Chemical compound O.Cl.C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 YCBPQSYLYYBPDW-UHFFFAOYSA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- AILRADAXUVEEIR-UHFFFAOYSA-N 5-chloro-4-n-(2-dimethylphosphorylphenyl)-2-n-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1P(C)(C)=O AILRADAXUVEEIR-UHFFFAOYSA-N 0.000 description 1
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- 229940000681 5-hydroxytryptophan Drugs 0.000 description 1
- HUNCSWANZMJLPM-UHFFFAOYSA-N 5-methyltryptophan Chemical compound CC1=CC=C2NC=C(CC(N)C(O)=O)C2=C1 HUNCSWANZMJLPM-UHFFFAOYSA-N 0.000 description 1
- RZVHIXYEVGDQDX-UHFFFAOYSA-N 9,10-anthraquinone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C(=O)C2=C1 RZVHIXYEVGDQDX-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- HDZZVAMISRMYHH-UHFFFAOYSA-N 9beta-Ribofuranosyl-7-deazaadenin Natural products C1=CC=2C(N)=NC=NC=2N1C1OC(CO)C(O)C1O HDZZVAMISRMYHH-UHFFFAOYSA-N 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 229940116375 B7-H4 antagonist Drugs 0.000 description 1
- 229940111018 BTLA antagonist Drugs 0.000 description 1
- 208000005440 Basal Cell Neoplasms Diseases 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 102100027138 Butyrophilin subfamily 3 member A1 Human genes 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 239000012275 CTLA-4 inhibitor Substances 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 235000002566 Capsicum Nutrition 0.000 description 1
- 240000008574 Capsicum frutescens Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 108010019673 Darbepoetin alfa Proteins 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 101100189828 Drosophila melanogaster Ebp gene Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- DVJAMEIQRSHVKC-BDAKNGLRSA-N Dutogliptin Chemical compound OB(O)[C@@H]1CCCN1C(=O)CN[C@H]1CNCC1 DVJAMEIQRSHVKC-BDAKNGLRSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- AFMYMMXSQGUCBK-UHFFFAOYSA-N Endynamicin A Natural products C1#CC=CC#CC2NC(C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C3)=C3C34OC32C(C)C(C(O)=O)=C(OC)C41 AFMYMMXSQGUCBK-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- LCDDAGSJHKEABN-MLGOLLRUSA-N Evogliptin Chemical compound C1CNC(=O)[C@@H](COC(C)(C)C)N1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F LCDDAGSJHKEABN-MLGOLLRUSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101710113436 GTPase KRas Proteins 0.000 description 1
- 208000002966 Giant Cell Tumor of Bone Diseases 0.000 description 1
- 208000000779 Gingival Neoplasms Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 102000018802 High Mobility Group Proteins Human genes 0.000 description 1
- 108010052512 High Mobility Group Proteins Proteins 0.000 description 1
- 108090000246 Histone acetyltransferases Proteins 0.000 description 1
- 102000003893 Histone acetyltransferases Human genes 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101001036313 Homo sapiens Axonemal dynein light intermediate polypeptide 1 Proteins 0.000 description 1
- 101000984934 Homo sapiens Butyrophilin subfamily 3 member A1 Proteins 0.000 description 1
- 101000906386 Homo sapiens Glutathione S-transferase omega-1 Proteins 0.000 description 1
- 101000829933 Homo sapiens Golgi SNAP receptor complex member 1 Proteins 0.000 description 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
- 101000852870 Homo sapiens Interferon alpha/beta receptor 1 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 1
- 101000945090 Homo sapiens Ribosomal protein S6 kinase alpha-3 Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 101150106931 IFNG gene Proteins 0.000 description 1
- 229940126060 IL-17A antagonist Drugs 0.000 description 1
- 102000026633 IL6 Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108010014726 Interferon Type I Proteins 0.000 description 1
- 102000002227 Interferon Type I Human genes 0.000 description 1
- 108010078049 Interferon alpha-2 Proteins 0.000 description 1
- 102100036714 Interferon alpha/beta receptor 1 Human genes 0.000 description 1
- 102100020989 Interferon lambda-2 Human genes 0.000 description 1
- 101710099622 Interferon lambda-2 Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108010043610 KIR Receptors Proteins 0.000 description 1
- 102100033627 Killer cell immunoglobulin-like receptor 3DL1 Human genes 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 239000002144 L01XE18 - Ruxolitinib Substances 0.000 description 1
- 239000002137 L01XE24 - Ponatinib Substances 0.000 description 1
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
- 208000000265 Lobular Carcinoma Diseases 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 108010047357 Luminescent Proteins Proteins 0.000 description 1
- 102000006830 Luminescent Proteins Human genes 0.000 description 1
- 206010025219 Lymphangioma Diseases 0.000 description 1
- 229920000877 Melamine resin Polymers 0.000 description 1
- 201000009574 Mesenchymal Chondrosarcoma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- 102100031455 NAD-dependent protein deacetylase sirtuin-1 Human genes 0.000 description 1
- PLILLUUXAVKBPY-SBIAVEDLSA-N NCCO.NCCO.CC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)\C1=N/NC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound NCCO.NCCO.CC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)\C1=N/NC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 PLILLUUXAVKBPY-SBIAVEDLSA-N 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 101710144111 Non-structural protein 3 Proteins 0.000 description 1
- CTYZDZBOBNKJOV-UHFFFAOYSA-N OC(=O)C(O)C(O)(C(O)=O)CC(O)=O.OC(=O)C(O)C(O)(C(O)=O)CC(O)=O Chemical compound OC(=O)C(O)C(O)(C(O)=O)CC(O)=O.OC(=O)C(O)C(O)(C(O)=O)CC(O)=O CTYZDZBOBNKJOV-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- VRSLTNZJOUZKLX-UHFFFAOYSA-N Ondansetron hydrochloride Chemical compound O.O.Cl.CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 VRSLTNZJOUZKLX-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 102100037602 P2X purinoceptor 7 Human genes 0.000 description 1
- 101710189965 P2X purinoceptor 7 Proteins 0.000 description 1
- 102100028045 P2Y purinoceptor 2 Human genes 0.000 description 1
- 101710096700 P2Y purinoceptor 2 Proteins 0.000 description 1
- 239000012270 PD-1 inhibitor Substances 0.000 description 1
- 239000012668 PD-1-inhibitor Substances 0.000 description 1
- 229940121678 PD-L2 antagonist Drugs 0.000 description 1
- 208000025618 Paget disease of nipple Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 208000008601 Polycythemia Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 102000000033 Purinergic Receptors Human genes 0.000 description 1
- 108010080192 Purinergic Receptors Proteins 0.000 description 1
- 101150040459 RAS gene Proteins 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 208000034541 Rare lymphatic malformation Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038111 Recurrent cancer Diseases 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 102100040756 Rhodopsin Human genes 0.000 description 1
- 108090000820 Rhodopsin Proteins 0.000 description 1
- 102100033643 Ribosomal protein S6 kinase alpha-3 Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 108010041191 Sirtuin 1 Proteins 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 229940123803 TIM3 antagonist Drugs 0.000 description 1
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- IWEQQRMGNVVKQW-OQKDUQJOSA-N Toremifene citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 IWEQQRMGNVVKQW-OQKDUQJOSA-N 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- PVNFMCBFDPTNQI-UIBOPQHZSA-N [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] acetate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 3-methylbutanoate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 2-methylpropanoate [(1S,2R,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] propanoate Chemical compound CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(C)=O)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2.CCC(=O)O[C@H]1CC(=O)N(C)c2cc(C\C(C)=C\C=C\[C@@H](OC)[C@@]3(O)C[C@H](OC(=O)N3)[C@@H](C)C3O[C@@]13C)cc(OC)c2Cl.CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)C(C)C)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2.CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)CC(C)C)[C@]2(C)OC2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2 PVNFMCBFDPTNQI-UIBOPQHZSA-N 0.000 description 1
- ZSTCHQOKNUXHLZ-PIRIXANTSA-L [(1r,2r)-2-azanidylcyclohexyl]azanide;oxalate;pentyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate;platinum(4+) Chemical compound [Pt+4].[O-]C(=O)C([O-])=O.[NH-][C@@H]1CCCC[C@H]1[NH-].C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 ZSTCHQOKNUXHLZ-PIRIXANTSA-L 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- PYOYNYIKNOJHFL-UHFFFAOYSA-N [[4-amino-6-[bis(hydroxymethyl)amino]-1,3,5-triazin-2-yl]amino]methanol Chemical compound NC1=NC(NCO)=NC(N(CO)CO)=N1 PYOYNYIKNOJHFL-UHFFFAOYSA-N 0.000 description 1
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- QUHYUSAHBDACNG-UHFFFAOYSA-N acerogenin 3 Natural products C1=CC(O)=CC=C1CCCCC(=O)CCC1=CC=C(O)C=C1 QUHYUSAHBDACNG-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 description 1
- 229940119059 actemra Drugs 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229940060265 aldara Drugs 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229940083773 alecensa Drugs 0.000 description 1
- GYABBVHSRIHYJR-UHFFFAOYSA-N alectinib hydrochloride Chemical compound Cl.CCC1=CC=2C(=O)C(C3=CC=C(C=C3N3)C#N)=C3C(C)(C)C=2C=C1N(CC1)CCC1N1CCOCC1 GYABBVHSRIHYJR-UHFFFAOYSA-N 0.000 description 1
- 229940110282 alimta Drugs 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- RGHILYZRVFRRNK-UHFFFAOYSA-N anthracene-1,2-dione Chemical compound C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 RGHILYZRVFRRNK-UHFFFAOYSA-N 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- HJBWBFZLDZWPHF-UHFFFAOYSA-N apalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C2(CCC2)C(=O)N(C=2C=C(C(C#N)=NC=2)C(F)(F)F)C1=S HJBWBFZLDZWPHF-UHFFFAOYSA-N 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 description 1
- 229960001372 aprepitant Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940115115 aranesp Drugs 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 229940087620 aromasin Drugs 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 229960003005 axitinib Drugs 0.000 description 1
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
- 229940127053 azedra Drugs 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- FUKOGSUFTZDYOI-BMANNDLBSA-O beacopp protocol Chemical compound ClCCN(CCCl)P1(=O)NCCCO1.CNNCC1=CC=C(C(=O)NC(C)C)C=C1.O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3C(O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1.C([C@H](C[C@]1(C(=O)OC)C=2C(=C3C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)=CC=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)C(O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C FUKOGSUFTZDYOI-BMANNDLBSA-O 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 229940108502 bicnu Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 229950006844 bizelesin Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 201000011143 bone giant cell tumor Diseases 0.000 description 1
- 201000006491 bone marrow cancer Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- QYKQWFZDEDFELK-UHFFFAOYSA-N brassinin Chemical class C1=CC=C2C(CNC(=S)SC)=CNC2=C1 QYKQWFZDEDFELK-UHFFFAOYSA-N 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000003714 breast lobular carcinoma Diseases 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- 229950004272 brigatinib Drugs 0.000 description 1
- KVUAALJSMIVURS-QNTKWALQSA-L calcium;(2s)-2-[[4-[[(6s)-2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl]methylamino]benzoyl]amino]pentanedioate Chemical compound [Ca+2].C([C@@H]1N(C=O)C=2C(=O)N=C(NC=2NC1)N)NC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-QNTKWALQSA-L 0.000 description 1
- 229940088954 camptosar Drugs 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 238000009924 canning Methods 0.000 description 1
- PGMBSCDPACPRSG-SCSDYSBLSA-N capiri Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 PGMBSCDPACPRSG-SCSDYSBLSA-N 0.000 description 1
- 239000001390 capsicum minimum Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 108010021331 carfilzomib Proteins 0.000 description 1
- BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 description 1
- 229960002438 carfilzomib Drugs 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000007444 cell Immobilization Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000009667 cerebral sarcoma Diseases 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 238000004182 chemical digestion Methods 0.000 description 1
- 201000005217 chondroblastoma Diseases 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 229960000928 clofarabine Drugs 0.000 description 1
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 description 1
- AGVAZMGAQJOSFJ-UHFFFAOYSA-M cobalt(2+);[5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] 1-[3-[2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1h-corrin-21-id-3-yl]propanoylamino]propan-2 Chemical compound [Co+2].N#[C-].OCC1OC(N2C3=CC(C)=C(C)C=C3N=C2)C(O)C1OP(O)(=O)OC(C)CNC(=O)CCC1(C)C(CC(N)=O)C2[N-]\C1=C(C)/C(C(C\1(C)C)CCC(N)=O)=N/C/1=C\C(C(C/1(CC(N)=O)C)CCC(N)=O)=N\C\1=C(C)/C1=NC2(C)C(C)(CC(N)=O)C1CCC(N)=O AGVAZMGAQJOSFJ-UHFFFAOYSA-M 0.000 description 1
- 229960002271 cobimetinib Drugs 0.000 description 1
- RESIMIUSNACMNW-BXRWSSRYSA-N cobimetinib fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F RESIMIUSNACMNW-BXRWSSRYSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000007748 combinatorial effect Effects 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011340 continuous therapy Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 229940088547 cosmegen Drugs 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- IMBXRZKCLVBLBH-OGYJWPHRSA-N cvp protocol Chemical compound ClCCN(CCCl)P1(=O)NCCCO1.O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.C([C@H](C[C@]1(C(=O)OC)C=2C(=C3C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)=CC=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 IMBXRZKCLVBLBH-OGYJWPHRSA-N 0.000 description 1
- POQBJIOLWPDPJE-UHFFFAOYSA-N cyclohexane-1,2-diamine;platinum Chemical compound [Pt].NC1CCCCC1N POQBJIOLWPDPJE-UHFFFAOYSA-N 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 229960002465 dabrafenib Drugs 0.000 description 1
- 229940059359 dacogen Drugs 0.000 description 1
- LVXJQMNHJWSHET-AATRIKPKSA-N dacomitinib Chemical compound C=12C=C(NC(=O)\C=C\CN3CCCCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 LVXJQMNHJWSHET-AATRIKPKSA-N 0.000 description 1
- 229950002205 dacomitinib Drugs 0.000 description 1
- 229940126590 dalatumumab Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960003109 daunorubicin hydrochloride Drugs 0.000 description 1
- 230000000850 deacetylating effect Effects 0.000 description 1
- 229960002272 degarelix Drugs 0.000 description 1
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 description 1
- 229940070968 depocyt Drugs 0.000 description 1
- URLVCROWVOSNPT-QTTMQESMSA-N desacetyluvaricin Natural products O=C1C(CCCCCCCCCCCC[C@@H](O)[C@H]2O[C@@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@H](C)O1 URLVCROWVOSNPT-QTTMQESMSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 229960000605 dexrazoxane Drugs 0.000 description 1
- WVYXNIXAMZOZFK-UHFFFAOYSA-N diaziquone Chemical compound O=C1C(NC(=O)OCC)=C(N2CC2)C(=O)C(NC(=O)OCC)=C1N1CC1 WVYXNIXAMZOZFK-UHFFFAOYSA-N 0.000 description 1
- 229950002389 diaziquone Drugs 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- JXSJBGJIGXNWCI-UHFFFAOYSA-N diethyl 2-[(dimethoxyphosphorothioyl)thio]succinate Chemical compound CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC JXSJBGJIGXNWCI-UHFFFAOYSA-N 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- ZQGJCHHKJNSPMS-UHFFFAOYSA-L disodium;[6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].COC1=C(OC)C(OC)=CC(NC=2N=C(NC=3N=C4N(COP([O-])([O-])=O)C(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=C1 ZQGJCHHKJNSPMS-UHFFFAOYSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 150000004141 diterpene derivatives Chemical group 0.000 description 1
- 150000004625 docetaxel anhydrous derivatives Chemical class 0.000 description 1
- 229940115080 doxil Drugs 0.000 description 1
- 229950003693 dutogliptin Drugs 0.000 description 1
- AFMYMMXSQGUCBK-AKMKHHNQSA-N dynemicin a Chemical compound C1#C\C=C/C#C[C@@H]2NC(C=3C(=O)C4=C(O)C=CC(O)=C4C(=O)C=3C(O)=C3)=C3[C@@]34O[C@]32[C@@H](C)C(C(O)=O)=C(OC)[C@H]41 AFMYMMXSQGUCBK-AKMKHHNQSA-N 0.000 description 1
- 229940056913 eftilagimod alfa Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229960004137 elotuzumab Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000001861 endoscopic biopsy Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 230000006718 epigenetic regulation Effects 0.000 description 1
- 229940089118 epogen Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940085363 evista Drugs 0.000 description 1
- 229950011259 evogliptin Drugs 0.000 description 1
- 229940060343 evomela Drugs 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 229940043168 fareston Drugs 0.000 description 1
- 229940087861 faslodex Drugs 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 229940087476 femara Drugs 0.000 description 1
- 238000011354 first-line chemotherapy Methods 0.000 description 1
- 235000011990 fisetin Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 229940064300 fluoroplex Drugs 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229940011343 fusilev Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 1
- 229940020967 gemzar Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229960003607 granisetron hydrochloride Drugs 0.000 description 1
- 229940054519 granix Drugs 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 229940033776 hemangeol Drugs 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 229940088013 hycamtin Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229940096120 hydrea Drugs 0.000 description 1
- QYZRTBKYBJRGJB-UHFFFAOYSA-N hydron;1-methyl-n-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide;chloride Chemical compound Cl.C1=CC=C2C(C(=O)NC3CC4CCCC(C3)N4C)=NN(C)C2=C1 QYZRTBKYBJRGJB-UHFFFAOYSA-N 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
- 229960001176 idarubicin hydrochloride Drugs 0.000 description 1
- 229940090411 ifex Drugs 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 229940126546 immune checkpoint molecule Drugs 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 230000006054 immunological memory Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000002602 induced regulatory T cell Anatomy 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 229950004101 inotuzumab ozogamicin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010212 intracellular staining Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940065638 intron a Drugs 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- PDWUPXJEEYOOTR-JRGAVVOBSA-N iobenguane (131I) Chemical compound NC(N)=NCC1=CC=CC([131I])=C1 PDWUPXJEEYOOTR-JRGAVVOBSA-N 0.000 description 1
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229940011083 istodax Drugs 0.000 description 1
- FABUFPQFXZVHFB-PVYNADRNSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-PVYNADRNSA-N 0.000 description 1
- 229940111707 ixempra Drugs 0.000 description 1
- 229940045773 jakafi Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 229940103064 lipodox Drugs 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229950001290 lorlatinib Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000891 luminescent agent Substances 0.000 description 1
- 108010078259 luprolide acetate gel depot Proteins 0.000 description 1
- 229940087857 lupron Drugs 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229960004616 medroxyprogesterone Drugs 0.000 description 1
- 229940083118 mekinist Drugs 0.000 description 1
- JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 229940101533 mesnex Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000003990 molecular pathway Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- PBQZQTQFQFYBNJ-UHFFFAOYSA-N n-methoxybenzamide Chemical compound CONC(=O)C1=CC=CC=C1 PBQZQTQFQFYBNJ-UHFFFAOYSA-N 0.000 description 1
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 210000002501 natural regulatory T cell Anatomy 0.000 description 1
- 229940086322 navelbine Drugs 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229940080607 nexavar Drugs 0.000 description 1
- 229940099637 nilandron Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 229960001420 nimustine Drugs 0.000 description 1
- 229940030115 ninlaro Drugs 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 229940024847 odomzo Drugs 0.000 description 1
- 229960002450 ofatumumab Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- HYFHYPWGAURHIV-JFIAXGOJSA-N omacetaxine mepesuccinate Chemical compound C1=C2CCN3CCC[C@]43C=C(OC)[C@@H](OC(=O)[C@@](O)(CCCC(C)(C)O)CC(=O)OC)[C@H]4C2=CC2=C1OCO2 HYFHYPWGAURHIV-JFIAXGOJSA-N 0.000 description 1
- 229940099216 oncaspar Drugs 0.000 description 1
- 238000012634 optical imaging Methods 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 230000008621 organismal health Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 229960005184 panobinostat Drugs 0.000 description 1
- FWZRWHZDXBDTFK-ZHACJKMWSA-N panobinostat Chemical compound CC1=NC2=CC=C[CH]C2=C1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FWZRWHZDXBDTFK-ZHACJKMWSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229940121655 pd-1 inhibitor Drugs 0.000 description 1
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
- 229940106366 pegintron Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229960002087 pertuzumab Drugs 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229960001131 ponatinib Drugs 0.000 description 1
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 description 1
- 229960002183 ponatinib hydrochloride Drugs 0.000 description 1
- BWTNNZPNKQIADY-UHFFFAOYSA-N ponatinib hydrochloride Chemical compound Cl.C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 BWTNNZPNKQIADY-UHFFFAOYSA-N 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229940029359 procrit Drugs 0.000 description 1
- 150000003146 progesterones Chemical class 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 229940092597 prolia Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940021945 promacta Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 238000003498 protein array Methods 0.000 description 1
- 229940034080 provenge Drugs 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229940061969 rheumatrex Drugs 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 108010091666 romidepsin Proteins 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 description 1
- 108010017584 romiplostim Proteins 0.000 description 1
- 102200006532 rs112445441 Human genes 0.000 description 1
- 102200006531 rs121913529 Human genes 0.000 description 1
- 102200006537 rs121913529 Human genes 0.000 description 1
- 102200006539 rs121913529 Human genes 0.000 description 1
- 102200006538 rs121913530 Human genes 0.000 description 1
- 102200006540 rs121913530 Human genes 0.000 description 1
- 102200006541 rs121913530 Human genes 0.000 description 1
- 229950004707 rucaparib Drugs 0.000 description 1
- INBJJAFXHQQSRW-STOWLHSFSA-N rucaparib camsylate Chemical compound CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.CNCc1ccc(cc1)-c1[nH]c2cc(F)cc3C(=O)NCCc1c23 INBJJAFXHQQSRW-STOWLHSFSA-N 0.000 description 1
- JFMWPOCYMYGEDM-XFULWGLBSA-N ruxolitinib phosphate Chemical compound OP(O)(O)=O.C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 JFMWPOCYMYGEDM-XFULWGLBSA-N 0.000 description 1
- CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical compound OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229940058287 salicylic acid derivative anticestodals Drugs 0.000 description 1
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 229960000953 salsalate Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229940053186 sclerosol Drugs 0.000 description 1
- 238000011333 second-line chemotherapy Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229960003323 siltuximab Drugs 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 102000030938 small GTPase Human genes 0.000 description 1
- 108060007624 small GTPase Proteins 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 229960005325 sonidegib Drugs 0.000 description 1
- 229960000487 sorafenib tosylate Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229940068117 sprycel Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- INIBXSLTWQVIHS-ASACRTLUSA-O stanford v protocol Chemical compound ClCCN(C)CCCl.O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3C(O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1.C([C@H](C[C@]1(C(=O)OC)C=2C(=C3C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)=CC=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21.C([C@H](C[C@]1(C(=O)OC)C=2C(=C3C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)=CC=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)C(O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C INIBXSLTWQVIHS-ASACRTLUSA-O 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 230000009211 stress pathway Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 229940022873 synribo Drugs 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
- 229940081616 tafinlar Drugs 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 229940069905 tasigna Drugs 0.000 description 1
- 229940066453 tecentriq Drugs 0.000 description 1
- 229940061353 temodar Drugs 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000002105 tongue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- PXSOHRWMIRDKMP-UHFFFAOYSA-N triaziquone Chemical compound O=C1C(N2CC2)=C(N2CC2)C(=O)C=C1N1CC1 PXSOHRWMIRDKMP-UHFFFAOYSA-N 0.000 description 1
- 229960004560 triaziquone Drugs 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229940086984 trisenox Drugs 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- HDZZVAMISRMYHH-KCGFPETGSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HDZZVAMISRMYHH-KCGFPETGSA-N 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 229940094060 tykerb Drugs 0.000 description 1
- 230000010472 type I IFN response Effects 0.000 description 1
- 229940022919 unituxin Drugs 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- AUFUWRKPQLGTGF-FMKGYKFTSA-N uridine triacetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C=C1 AUFUWRKPQLGTGF-FMKGYKFTSA-N 0.000 description 1
- 229960003498 uridine triacetate Drugs 0.000 description 1
- LFOHPKKMDYSRLY-UHFFFAOYSA-N uridine triacetate Natural products CC(=O)OCC1OC(CN2C=CC(=O)NC2=O)C(OC(=O)C)C1OC(=O)C LFOHPKKMDYSRLY-UHFFFAOYSA-N 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- WJHZBTMHUNVIKC-UHFFFAOYSA-N valerylsalicylic acid Chemical compound CCCCC(=O)OC1=CC=CC=C1C(O)=O WJHZBTMHUNVIKC-UHFFFAOYSA-N 0.000 description 1
- ATCJTYORYKLVIA-SRXJVYAUSA-N vamp regimen Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C(C45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 ATCJTYORYKLVIA-SRXJVYAUSA-N 0.000 description 1
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 description 1
- 229960001183 venetoclax Drugs 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 229940065658 vidaza Drugs 0.000 description 1
- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- 229960002166 vinorelbine tartrate Drugs 0.000 description 1
- GBABOYUKABKIAF-IWWDSPBFSA-N vinorelbinetartrate Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC(C23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IWWDSPBFSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940069559 votrient Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 229940014556 xgeva Drugs 0.000 description 1
- 229940055760 yervoy Drugs 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229940072018 zofran Drugs 0.000 description 1
- 229940033942 zoladex Drugs 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
- 229940061261 zolinza Drugs 0.000 description 1
- 229940002005 zometa Drugs 0.000 description 1
- 229940051084 zytiga Drugs 0.000 description 1
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/132—Amines having two or more amino groups, e.g. spermidine, putrescine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
Description
、インターロイキン−2(アルデスロイキン)、イントロンA(組換え型インターフェロンアルファ−2b)、イオベングアンI 131、イピリムマブ、イレッサ(ゲフィチニブ)、塩酸イリノテカン、イリノテカン塩酸塩リポソーム、イストダックス(ロミデプシン)、イボシデニブ、イクサベピロン、クエン酸イクサゾミブ、イクセンプラ(イクサベピロン)、ジャカフィ(ルキソリチニブリン酸)、JEB、ジェブタナ(カバジタキセル)、カドシラ(アド−トラスツズマブエムタンシン)、ケピバンス(パリフェルミン)、キイトルーダ(ペムブロリズマブ)、キスカリ(リボシクリブ)、キムリア(チサゲンレクロイセル)、カイプロリス(カルフィルゾミブ)、酢酸ランレオチド、ラパチニブジトシレート、ラロトレクチニブ硫酸塩、ラルトゥルボ(オララツマブ)、レナリドミド、レンバチニブメシル酸塩、レンビマ(レンバチニブメシル酸塩)、レトロゾール、ロイコボリンカルシウム、ロイケラン(クロラムブシル)、酢酸ロイプロリド、レブランケラスティック(アミノレブリン酸)、リブタヨ(セミプリマブ−rwlc)、リポドックス(ドキソルビシン塩酸塩リポソーム)、ロムスチン、ロンサーフ(トリフルリジン及びチピラシル塩酸塩)、ロルブレナ(ロルラチニブ)、ロルラチニブ、ルモキシチ(モキセツモマブパスドトックス−tdfk)、ルプロン(酢酸ロイプロリド)、ルプロンデポー(酢酸ロイプロリド)、ルタセラ(ルテチウムLu177−ドタテート)、ルテチウム(Lu177−ドタテート)、リンパルザ(オラパリブ)、マルキボ(ビンクリスチン硫酸リポソーム)、マツラン(塩酸プロカルバジン)、塩酸メクロレタミン、酢酸メゲストロール、メキニスト(トラメチニブ)、メクトビ(ビニメチニブ)、メルファラン、メルファラン塩酸塩、メルカプトプリン、メスナ、メスネックス(メスナ)、メトトレキサート、臭化メチルナルトレキソン、ミドスタウリン、マイトマイシンC、塩酸ミトキサントロン、モガムリズマブ−kpkc、モキセツモマブパスドトックス−tdfk、モゾビル(プレリキサフォル)、ムスタゲン(塩酸メクロレタミン)、MVAC、ミレラン(ブスルファン)、マイロターグ(ゲムツズマブオゾガマイシン)、ナノ粒子パクリタキセル(パクリタキセルアルブミン安定化ナノ粒子製剤)、ナベルビン、(酒石酸ビノレルビン)、ネシツムマブ、ネララビン、マレイン酸ネラチニブ、ネルリンクス(マレイン酸ネラチニブ)、ネツピタント及びパロノセトロンの塩酸塩、ノイラスタ(ペグフィルグラスチム)、ニューポジェン(フィルグラスチム)、ネクサバール(ソラフェニブトシレート)、ニランドロン(ニルタミド)、ニロチニブ、ニルタミド、ニンラロ(クエン酸イクサゾミブ)、ニラパリブトシレート一水和物、ニボルマブ、エヌプレート(ロミプロスチム)、オビヌツズマブ、オドムゾ(ソニデジブ)、OEPA、オファツムマブ、OFF、オラパリブ、オララツマブ、オマセタキシンメペスクシナート、オンカスパー(ペガスパルガーゼ)、塩酸オンダンセトロン、オニビデ(イリノテカン塩酸塩リポソーム)、オンタク(デニロイキンディフチトックス)、オプジーボ(ニボルマブ)、OPPA、オシメルチニブ、オキサリプラチン、パクリタキセル、パクリタキセルアルブミン安定化ナノ粒子製剤(nab−パクリタキセル)、PAD、パルボシクリブ、パリフェルミン、塩酸パロノセトロン、塩酸パロノセトロン及びネツピタント、パミドロネート二ナトリウム、パニツムマブ、パノビノスタット、塩酸パゾパニブ、PCV、PEB、ペガスパルガーゼ、ペグフィルグラスチム、ペグインターフェロンアルファ−2b、PEG−イントロン(ペグインターフェロンアルファ−2b)、ペンブロリズマブ、ペメトレキセド二ナトリウム、ペルジェタ(ペルツズマブ)、ペルツズマブ、プレリキサフォー、ポマリドマイド、ポマリスト(ポマリドマイド)、塩酸ポナチニブ、ポルトラザ(ネシツムマブ)、ポテリジオ(モガムリズマブ−kpkc)、プララトレキサート、プレドニゾン、プロカルバジン塩酸塩、プロクリット(エポエチンアルファ)、プロロイキン(アルデスロイキン)、プロリア(デノスマブ)、プロマクタ(エルトロンボパグオラミン)、塩酸プロプラノロール、プロベンジ(シプロイセルT)、プリネトール(メルカプトプリン)、プリキサン(メルカプトプリン)、二塩化ラジウム223、塩酸ラロキシフェン、ラムシルマブ、ラスブリカーゼ、ラヴリズマブ−cwvz、R−CHOP、R−CVP、組換えヒトパピローマウイルス(HPV)の二価ワクチン、組換えヒトパピローマウイルス(HPV)の無価ワクチン、組換えヒトパピローマウイルス(HPV)4価ワクチン、組換えインターフェロンアルファ−2b、レゴラフェニブ、レリストール(臭化メチルナルトレキソン)、R−エポック、レタクリット(エポエチンアルファ)、レブリミド(レナリドミド)、リウマトレックス(メトトレキサート)、リボシクリブ、R−ICE、リツキサン(リツキシマブ)、リツキサンハイセラ(リツキシマブ及びヒアルロニダーゼ ヒト)、リツキシマブ、リツキシマブ及びヒアルロニダーゼ ヒト、ロラピタント塩酸塩、ロミデプシン、ロミプロスチム、ルビドマイシン(塩酸ダウノルビシン)、ルブラカ(ルカパリブカムシレート)、ルカパリブカムシレート、リン酸ルキソリチニブ、リダプト(ミドスタウリン)、サンクソ(グラニセトロン)、スクレロゾル胸膜内エアロゾル(タルク)、シルツキマブ、シプロイセル−T、ソマチュリンデポー(酢酸ランレオチド)、ソニデギブ、ソラフェニブトシレート、スプリセル(ダサチニブ)、スタンフォードV、滅菌タルク粉末(タルク)、ステリタクル(タルク)、スチバーガ(レゴラフェニブ)、リンゴ酸スニチニブ、サストール(グラニセトロン)、ステント(スニチニブリンゴ酸塩)、シラトロン(ペグインターフェロンアルファ−2b)、シルバント(シルツキシマブ)、シンリボ(オマセタキシンメペサクシネート)、タブロイド(チオグアニン)、TAC、タフィンラー(ダブラフェニブ)、タグラクソフスプ−erzs、タグリッソ(オシメルチニブ)、タルク、タリモジーン・ラハーパレプベック、クエン酸タモキシフェン、タラビンPFS(シタラビン)、タルセバ(エルロチニブ塩酸塩)、タルグレチン(ベキサロテン)、タシグナ(ニロチニブ)、タバリセ(フォスタマチニブ二ナトリウム)、タキソール(パクリタキセル)、タキソテール(ドセタキセル)、テセントリク(アテゾリズマブ)、テモダール(テモゾロミド)、テモゾロミド、テムシロリムス、サリドマイド、サロミド(サリドマイド)、チオグアニン、チオテパ、チブソボ、(イボシデニブ)、チサゲンレクロイセル、トシリズマブ、トラク(フルオロウラシル−局所)、塩酸トポテカン、トレミフェン、トリセル(テムシロリムス)、トテクト(デクスラゾキサン塩酸塩)、TPF、トラベクテジン、トラメチニブ、トラスツズマブ、トレアンダ(ベンダムスチン塩酸塩)、トレキサール(メトトレキサート)、トリフルリジン及びチピラシル塩酸塩、トリセノックス(三酸化ヒ素)、タイケルブ、(ラパチニブジトシレート)、ウルトミリス(ラヴリズマブ−cwvz)、ユニツキシン(ジヌツキシマブ)、三酢酸ウリジン、VAC、バルルビシン、バルスター(バルルビシン)、バンデタニブ、VAMP、バルビ(塩酸ロラピタント)、ベクチビックス(パニツムマブ)、VeIP、ベルケイド(ボルテゾミブ)、ベムラフェニブ、ベンクレキセタ(Venclexta)(ベネトクラクス)、ベネトクラクス、ベージニオ(アベマシクリブ)、ビダザ(アザシチジン)、ビンブラスチン硫酸塩、ビンクリスチン硫酸塩、ビンクリスチン硫酸塩リポソーム、ビノレルビン酒石酸塩、VIP、ビスモデギブ、ビストガード(ウリジン三酢酸)、ビトラクビ(ラロトレクチニブ硫酸塩)、ビジンプロ(ダコミチニブ)、ボラキサゼ(グルカルピダーゼ)、ボリノスタット、ヴォトリエント(塩酸パゾパニブ)、ヴィキセオス(塩酸ダウノルビシン及びシタラビンリポソーム)、ザーコリ(クリゾチニブ)、ゼローダ(カペシタビン)、ゼリイリ(XELIRI)、ゼロックス(XELOX)、ザイゲバ(Xgeva)(デノスマブ)、ゾーフィゴ(二塩化ラジウム223)、ゾスパタ(フマル酸ギルテリチニブ)、イクスタンジ(エンザルタミド)、ヤーボイ(イピリムマブ)、イエスカルタ(アキシカブタジンシロルーセル)、ヨンデリス(トラベクテジン)、ザルトラップ(Ziv−アフリベルセプト)、ザルシオ(フィルグラスチム)、ゼジュラ(ニラパリブトシレート一水和物)、ゼルボラフ(ベムラフェニブ)、ゼバリン(イブリツモマブチウキセタン)、ザインカード(デクスラゾキサン塩酸塩)、Ziv−アフリベルセプト、ゾフラン(塩酸オンダンセトロン)、ゾラデックス(酢酸ゴセレリン)、ゾレドロン酸、ゾリンザ(ボリノスタット)、ゾメタ(ゾレドロン酸)、ザイデリグ(イデラリシブ)、ザイカディア(セリチニブ)、ザイティガ(アビラテロンアセテート)、シクロホスファミド、ドラスタチン、パンクラチスタチン、メクロレタミン、ブレオマイシン、ダクチノマイシン、ダウノルビシン、ドキソルビシン、モルホリノドキソルビシン、シアノモルホリノドキソルビシン、2−ピロリノ−ドキソルビシン、デオキシドキソルビシン、エピルビシン、イダルビシン、5−フルオロウラシル(5−FU)、トリメトレキサート、エポチロン、ロニダミン、メイタンシン、ミトキサントロン、PSK多糖複合体、ベルカリンA、ビンデシン、シトシンアラビノシド(「Ara−C」)、パクリタキセル、ドセタキセル、nab−パクリタキセル、6−チオグアニン、シスプラチン、オキサリプラチン、カルボプラチン、ビンブラスチン、白金、アンサミトシン、ビンクリスチン、ビノレルビン、ノバントロン(ミトキサントロン)、ダウノマイシン(=ダウノルビシン)、イリノテカン(例えば、CPT−11)、レチノイン酸、ボルテゾミブ、ジギトキシン、ジゴキシン、パツピロン、ヒペリシン、セツキシマブ、セプタシジン、ヘダマイシン、CDDP、マイトマイシンC、テモゾロミド及びペメトレキセドからなるリストAから選択される少なくとも1種の薬剤である。
−シスプラチン、オキサリプラチン及びカルボプラチンから選択される白金配位錯体;
−パクリタキセル、nab−パクリタキセル、ドセタキセル及びタキソテールから選択されるタキサン類;
−ビンデシン、ビンブラスチン、ビンクリスチン及びビノレルビンから選択されるビンカアルカロイド;並びに
−ミトキサントロンダウノルビシン、ドキソルビシン、エピルビシン、イダルビシン、バルルビシン及びジトリサルビシンから選択されるアントラサイクリン類;
−ゲムシタビン
−ペメトレキセド
−それらの混合物及びそれらの医薬として許容される塩、
からなるリストEから選択される。
−シスプラチン、オキサリプラチン及びカルボプラチンから選択される白金配位錯体;
―パクリタキセル、nab−パクリタキセル、ドセタキセル及びタキソテールから選択されるタキサン類;
―ミトキサントロン、ダウノルビシン、ドキソルビシン、エピルビシン、イダルビシン、バルルビシン及びジトリサルビシンから選択されるアントラサイクリン類;並びに
―それらの混合物及びそれらの医薬として許容される塩、
からなるリストFから選択される。
−シスプラチン、オキサリプラチン及びカルボプラチン;又はカルボプラチン及びペメトレキセドの同時若しくは逐次投与;又はオキサリプラチン及び5−FUの同時若しくは逐次投与
−パクリタキセル、nab−パクリタキセル、ドセタキセル及びタキソテールから選択されるタキサン類
−ゲムシタビン
―5−FU
−ペメトレキセド
―ミトキサントロン、ドキソルビシン、ドキソルビシン、エピルビシン、イダルビシン、バルルビシン及びジトリサルビシンから選択されるアントラサイクリン類;並びにそれらの混合物及びそれらの医薬として許容される塩、
からなるリストGから選択される。
−シスプラチン、オキサリプラチン及びカルボプラチン;又はカルボプラチン及びペメトレキセドの同時若しくは逐次投与;又はオキサリプラチン及び5−FUの同時若しくは逐次投与
―パクリタキセル、nab−パクリタキセル、ドセタキセル及びタキソテールから選択されるタキサン類
―ゲムシタビン
―ペメトレキセド
―ミトキサントロン;並びに
―それらの混合物及びそれらの医薬として許容される塩、
からなるリストHから選択される。
−ニボルマブ、ペンブロリズマブ及びピディリズマブなどのPD−1アンタゴニスト
−アベルマブ、BMS−93659、CA−170、デュルバルマブ、MCLA−145、SP142、STI−A1011、STIA1012、STI−A1010、STI−A1014、A110、KY1003及びアテゾリムマブなどのPD−L1アンタゴニスト、
−トレメリムマブ及びイピリムマブなどのCTLA−4アンタゴニスト、並びに
−それらの混合物、
から選択される。
a)前述の少なくとも1つのCRMを含む組成物の第1の投与、その後、毎日同じものを投与すること;次いで
b)工程(a)による第1の投与後少なくとも12時間、典型的には24又は48時間の時点で、少なくとも1つの化学療法剤を最初に投与し、その後、医療プロトコルによって定義されるように化学療法の毎日又は毎週の投与を行うこと、
c)工程(a)による第1の投与後少なくとも12時間、典型的には24又は48時間の時点で、少なくとも1つの免疫チェックポイント阻害剤を最初に投与し、その後、医療プロトコルによって定義されるように少なくとも1つの免疫チェックポイント阻害剤の毎日又は毎週の投与を行うこと、
を含む。当業者は、(b)又は(c)による第1及び/又はその後の投与が、同時に、連続的に又は間欠的に投与されるべきかどうかを定義することができる。
方法:
マウスの株及び小屋。6〜8週齢の野生型雌C57Bl/6マウスを、Envigo RMS SARL(Gannat,France)から入手した。動物を、12時間の光と12時間の暗闇のサイクルで、食餌及び水を自由に摂取できる温度制御された環境下で、特定の病原体を含まない状態で維持した(特に明確でない限り)。動物実験は、EU指令63/2010に準拠しており、Cordeliers Research Center(Paris,France)の倫理委員会によって承認された。全てのマウス実験をランダム化し、盲検にし、統計的に有意な効果を検出するために試料サイズを計算した。
酢酸メドロキシプロゲステロン(MPA)放出ペレットを移植し、続いて次の6週間、DNA損傷剤の7,12−ジメチルベンズ[a]アントラセン(DMBA)を経管栄養することにより、若い(7週齢)雌BALB/cマウスに乳癌を誘導した。最後のDMBA注射と触診可能な乳癌病変の発現の間の間隔は、むしろ様々であることに留意されたい。触診可能な腫瘍が出現した時に、マウスを異なる実験グループにランダム化し、d−1及びd0の時点でヒドロキシクエン酸塩(100mg/kg)の腹腔内注射、並びに/又は5.17mg/kgのミトキサントロンの腹腔内注射で治療した。次いで、中和抗CD11b抗体(クローンM1/70、BioXCell(商標)からのrefBE0007)又はそれらのアイソタイプ対照(BioXCell(商標)からのクローンLTF−2、refBE0090)を、d−1、d0及びd7の時点で注射した。式:長さ×幅を用いて腫瘍表面(mm2)を計算することによって腫瘍成長を経過観察した。
化学療法後の3又は11日目(d3又はd11)に、マウスを安楽死させ、腫瘍を取り出し、予め1mlのDMEM又はRPMI培地で満たしたgentleMACS C管(Miltenyi Biotec(商標)からのref130−096−334)に入れ、すぐに氷上に置いた。機械的消化(鋏付き)及び化学的消化(腫瘍解離キット及びgentleMACS Octo解離剤による、Miltenyi Biotec(商標)からのそれぞれref130−096−730及び130−096−427)、腫瘍を濾過し(MACS smartstrainers 70μM、Miltenyi Biotec(商標)からのref130−110−916を使用して)、PBSで2回洗浄し、96穴丸底板に分散させた。
実施例1
化学療法と飢餓の組み合わせによる免疫チェックポイントの感作。皮下の位置で発達する触診可能な同系腫瘍(平均20mm3)を有する免疫適格性マウスを、最初に全身化学療法単独(ミトキサントロン、MTX、腹腔内注射(i.p.)、若しくはビヒクル対照としてPBS)で治療するか、又は絶食計画(化学療法前48時間)と組み合わせて治療し、次いで、図1Aに概略的に示されるように、免疫療法(CTLA−4若しくはPD−1を遮断する抗体)又はアイソタイプ対照抗体のいずれかを投与するグループにランダム化する。腫瘍成長を連続的に監視した。実験の終点で最も高頻度に腫瘍を含まないマウスをもたらした組み合わせ療法(化学療法の日として定義した0日後から50日目)は、飢餓、化学療法及び免疫療法を組み合わせて利用したものであった。腫瘍の根絶につながる完全な応答は、他のグループ(PBS対照、MTX+アイソタイプ、MTX+HC、MTX+免疫療法)のいずれかにおいて全く又はほとんど見られなかった(図1B〜F)。それゆえ、3つの組み合わせ計画(飢餓、化学療法及び免疫療法)は、癌の消失につながるユニークな能力を有する。
CD11b遮断は、化学療法と組み合わしたヒドロキシクエン酸の抗癌作用と干渉する。プロゲステロン類似体のメドロキシプロゲステロンと、2,4−ジメトキシベンズアルデヒド(DMBA)を用いた経管栄養による反復DNA損傷の組み合わせは、若い雌BALB/cマウスに投与した場合に、乳癌を誘導するのに非常に効率的である(図示せず)。このモデルでは、ミトキサントロン(MTX)ベースの化学療法とCRMヒドロキシクエン酸(HC)の組み合わせは、腫瘍の成長を低下させ、マウスの生存を延長するのに非常に効率的であり(データ示さず)、MTX及びHC単独よりもはるかにより効率的である。これらの結果は、触診により診断でき、表面が25mm2に達した時に治療が開始される「現実的な」状況で得られた。留意すべきは、骨髄細胞のCD11b依存的血管外漏出を阻止するモノクローナル抗体(M1/70)の繰り返し注射は、HC+MTXによる腫瘍成長低下と顕著に干渉した(データ示さず)。免疫適格性C57Bl/6マウスでの移植可能なMCA205線維肉腫モデルにおいて、非常に類似した結果が得られた(データ示さず)。再び、HC+MTXによる併用治療は、MTX単独よりも腫瘍成長の低下と生存の延長により成功し、この治療の有効性はCD11b遮断によって低下した(データ示さず)。
さらなるインビボ実験を以下に詳述したように行う。
インビボ実験。XMCA205/MC38/PC3/TC1腫瘍細胞(100μlのPBS中)の皮下/同所性注射により、マウスの右脇/同所性位置に腫瘍移植を行った。腫瘍体積を、デジタルキャリパーを使用して監視し、式:体積=長さ×幅×高さ/8×4/3πに従って、又は適切な撮像モデル(CTスキャン、PETスキャン、蛍光撮像)によって計算した。腫瘍が平均して20mm3に達したら、マウスを絶食させるか(餌はないが、水は自由に摂取できる状態で48時間)又はヒドロキシクエン酸塩(HC:飲料水中の5mg/ml、毎日)などのカロリー制限模倣物(CRM)を与えるか、又はミトキサントロン(MTX;200μlのPBS中5.17mg/kgのi.p.)、オキサリプラチン、カルボプラチン+ペメトレキセド、オキサリプラチン+5FU、又はパクリタキセル/Nabパクリタキセル、又は免疫チェックポイント阻害剤(ICI)の抗PD−1(200μlのPBS中10mg/kgのi.p.)、及び/又は抗CTLA−4(200μl/PBS中の5mg/kgのi.p.)、又はIDOアンタゴニスト又はVISTAアンタゴニスト又はTIM3アンタゴニスト又はLAG3アンタゴニストで治療した。腫瘍の大きさを、MTX/Chemo後50日まで注意深く監視した。治癒したマウスの治療により誘導された抗腫瘍性免疫を、一方の脇に同じ腫瘍(同系MCA205/MC38/PC3/TC1細胞)を皮下に再移植することにより負荷するが、抗原的に無関係の癌(3×105個の同系TC1/MCA205又は他の細胞)を反対側の脇に移植した。
多施設、3アーム、ランダム化、二重盲検、プラセボ対照第II相を、ペンブロリズマブ、カルボプラチン及びペメトレキセドで治療した転移性非扁平非小細胞肺癌(NSLCC)におけるカロリー制限模倣物(ヒドロキシクエン酸(HC)±α−リポ酸(ALA)の臨床的影響を評価するために設計する。
ランダム化した患者は、標準的な臨床実施(すなわち、追加の検査なし)に従って経過観察する。
アームA:α−リポ酸(ALA、600mg 3x/j,経口、朝昼及び夜)+ヒドロキシクエン酸(HC、用量800mg×3/j、朝昼及び夜)
アームB:HC(+ALA適合プラセボ)
アームC:適合プラセボ
を投与する。
癌の完全かつ永久的な治癒は、実現不可能な目標である。抗新生物の完全な有効性は、齧歯類モデルでも達成することが困難である。ここで、本発明者らは、絶食又はCRMと化学療法の組み合わせが、腫瘍担持マウスを免疫療法に感作させ、したがって、巨視的な癌の持続的な消失を達成することを可能にするという証拠を提供する。そのような組み合わせ療法(絶食又はCRM+化学療法+免疫療法)は、治療したマウスのかなりの割合で確立した癌の永久的な消失をもたらし、保護的な抗癌性免疫応答を誘導する。
本出願全体において、本発明が属する技術分野の状態を様々な参考文献が説明している。これらの参考文献の開示は、参照により本開示に組み込まれる。
1. F. Madeo, F. Pietrocola, T. Eisenberg, G. Kroemer, Caloric restriction mimetics: towards a molecular definition. Nat Rev Drug Discov 13, 727-740 (2014).
2. G. Marino, F. Pietrocola, T. Eisenberg, Y. Kong, S. A. Malik, A. Andryushkova, S. Schroeder, T. Pendl, A. Harger, M. Niso-Santano, N. Zamzami, M. Scoazec, S. Durand, D. P. Enot, A. F. Fernandez, I. Martins, O. Kepp, L. Senovilla, C. Bauvy, E. Morselli, E. Vacchelli, M. Bennetzen, C. Magnes, F. Sinner, T. Pieber, C. Lopez-Otin, M. C. Maiuri, P. Codogno, J. S. Andersen, J. A. Hill, F. Madeo, G. Kroemer, Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol Cell 53, 710-725 (2014).
3. F. Pietrocola, F. Castoldi, M. Markaki, S. Lachkar, G. Chen, D. Enot, S. Durand, N. Bossut, M. Tong, S. Malik, F. Loos, N. Dupont, G. Marino, N. Abdelkader, F. Madeo, M. Maiuri, R. Kroemer, P. Codogno, J. Sadoshima, N. Tavernarakis, G. Kroemer, Aspirin Recapitulates Features of Caloric Restriction. Cell Rep, (2018).
4. F. Pietrocola, S. Lachkar, D. P. Enot, M. Niso-Santano, J. M. Bravo-San Pedro, V. Sica, V. Izzo, M. C. Maiuri, F. Madeo, G. Marino, G. Kroemer, Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ 22, 509-516 (2015).
5. M. Lakshminarasimhan, D. Rauh, M. Schutkowski, C. Steegborn, Sirt1 activation by resveratrol is substrate sequence-selective. Aging (Albany NY) 5, 151-154 (2013).
6. M. Gertz, G. T. Nguyen, F. Fischer, B. Suenkel, C. Schlicker, B. Franzel, J. Tomaschewski, F. Aladini, C. Becker, D. Wolters, C. Steegborn, A molecular mechanism for direct sirtuin activation by resveratrol. PLoS One 7, e49761 (2012).
7. J. M. Villalba, F. J. Alcain, Sirtuin activators and inhibitors. Biofactors 38, 349-359 (2012).
8. M. T. Borra, B. C. Smith, J. M. Denu, Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 280, 17187-17195 (2005).
9. F. Pietrocola, J. Pol, E. Vacchelli, S. Rao, D. P. Enot, E. E. Baracco, S. Levesque, F. Castoldi, N. Jacquelot, T. Yamazaki, L. Senovilla, G. Marino, F. Aranda, S. Durand, V. Sica, A. Chery, S. Lachkar, V. Sigl, N. Bloy, A. Buque, S. Falzoni, B. Ryffel, L. Apetoh, F. Di Virgilio, F. Madeo, M. C. Maiuri, L. Zitvogel, B. Levine, J. M. Penninger, G. Kroemer, Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell 30, 147-160 (2016).
10. L. Galluzzi, A. Buque, O. Kepp, L. Zitvogel, G. Kroemer, Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol 17, 97-111 (2017).
11. N. Bloy, P. Garcia, C. M. Laumont, J. M. Pitt, A. Sistigu, G. Stoll, T. Yamazaki, E. Bonneil, A. Buque, J. Humeau, J. W. Drijfhout, G. Meurice, S. Walter, J. Fritsche, T. Weinschenk, H. G. Rammensee, C. Melief, P. Thibault, C. Perreault, J. Pol, L. Zitvogel, L. Senovilla, G. Kroemer, Immunogenic stress and death of cancer cells: Contribution of antigenicity vs adjuvanticity to immunosurveillance. Immunol Rev 280, 165-174 (2017).
12. E. Vacchelli, Y. Ma, E. E. Baracco, A. Sistigu, D. P. Enot, F. Pietrocola, H. Yang, S. Adjemian, K. Chaba, M. Semeraro, M. Signore, A. De Ninno, V. Lucarini, F. Peschiaroli, L. Businaro, A. Gerardino, G. Manic, T. Ulas, P. Gunther, J. L. Schultze, O. Kepp, G. Stoll, C. Lefebvre, C. Mulot, F. Castoldi, S. Rusakiewicz, S. Ladoire, L. Apetoh, J. M. Bravo-San Pedro, M. Lucattelli, C. Delarasse, V. Boige, M. Ducreux, S. Delaloge, C. Borg, F. Andre, G. Schiavoni, I. Vitale, P. Laurent-Puig, F. Mattei, L. Zitvogel, G. Kroemer, Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1. Science 350, 972-978 (2015).
13. A. Sistigu, T. Yamazaki, E. Vacchelli, K. Chaba, D. P. Enot, J. Adam, I. Vitale, A. Goubar, E. E. Baracco, C. Remedios, L. Fend, D. Hannani, L. Aymeric, Y. Ma, M. Niso-Santano, O. Kepp, J. L. Schultze, T. Tuting, F. Belardelli, L. Bracci, V. La Sorsa, G. Ziccheddu, P. Sestili, F. Urbani, M. Delorenzi, M. Lacroix-Triki, V. Quidville, R. Conforti, J. P. Spano, L. Pusztai, V. Poirier-Colame, S. Delaloge, F. Penault-Llorca, S. Ladoire, L. Arnould, J. Cyrta, M. C. Dessoliers, A. Eggermont, M. E. Bianchi, M. Pittet, C. Engblom, C. Pfirschke, X. Preville, G. Uze, R. D. Schreiber, M. T. Chow, M. J. Smyth, E. Proietti, F. Andre, G. Kroemer, L. Zitvogel, Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 20, 1301-1309 (2014).
14. M. Michaud, I. Martins, A. Q. Sukkurwala, S. Adjemian, Y. Ma, P. Pellegatti, S. Shen, O. Kepp, M. Scoazec, G. Mignot, S. Rello-Varona, M. Tailler, L. Menger, E. Vacchelli, L. Galluzzi, F. Ghiringhelli, F. di Virgilio, L. Zitvogel, G. Kroemer, Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334, 1573-1577 (2011).
15. G. Kroemer, L. Galluzzi, O. Kepp, L. Zitvogel, Immunogenic cell death in cancer therapy. Annu Rev Immunol 31, 51-72 (2013).
16. Y. Ma, L. Aymeric, C. Locher, S. R. Mattarollo, N. F. Delahaye, P. Pereira, L. Boucontet, L. Apetoh, F. Ghiringhelli, N. Casares, J. J. Lasarte, G. Matsuzaki, K. Ikuta, B. Ryffel, K. Benlagha, A. Tesniere, N. Ibrahim, J. Dechanet-Merville, N. Chaput, M. J. Smyth, G. Kroemer, L. Zitvogel, Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy. J Exp Med 208, 491-503 (2011).
17. F. Ghiringhelli, L. Apetoh, A. Tesniere, L. Aymeric, Y. Ma, C. Ortiz, K. Vermaelen, T. Panaretakis, G. Mignot, E. Ullrich, J. L. Perfettini, F. Schlemmer, E. Tasdemir, M. Uhl, P. Genin, A. Civas, B. Ryffel, J. Kanellopoulos, J. Tschopp, F. Andre, R. Lidereau, N. M. McLaughlin, N. M. Haynes, M. J. Smyth, G. Kroemer, L. Zitvogel, Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15, 1170-1178 (2009).
18. L. Apetoh, F. Ghiringhelli, A. Tesniere, M. Obeid, C. Ortiz, A. Criollo, G. Mignot, M. C. Maiuri, E. Ullrich, P. Saulnier, H. Yang, S. Amigorena, B. Ryffel, F. J. Barrat, P. Saftig, F. Levi, R. Lidereau, C. Nogues, J. P. Mira, A. Chompret, V. Joulin, F. Clavel-Chapelon, J. Bourhis, F. Andre, S. Delaloge, T. Tursz, G. Kroemer, L. Zitvogel, Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13, 1050-1059 (2007).
19. M. Obeid, A. Tesniere, F. Ghiringhelli, G. M. Fimia, L. Apetoh, J. L. Perfettini, M. Castedo, G. Mignot, T. Panaretakis, N. Casares, D. Metivier, N. Larochette, P. van Endert, F. Ciccosanti, M. Piacentini, L. Zitvogel, G. Kroemer, Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13, 54-61 (2007).
20. W. H. Fridman, L. Zitvogel, C. Sautes-Fridman, G. Kroemer, The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol 14, 717-734 (2017).
21. J. M. Pitt, G. Kroemer, L. Zitvogel, Immunogenic and Non-immunogenic Cell Death in the Tumor Microenvironment. Adv Exp Med Biol 1036, 65-79 (2017).
22. C. Pfirschke, C. Engblom, S. Rickelt, V. Cortez-Retamozo, C. Garris, F. Pucci, T. Yamazaki, V. Poirier-Colame, A. Newton, Y. Redouane, Y. J. Lin, G. Wojtkiewicz, Y. Iwamoto, M. Mino-Kenudson, T. G. Huynh, R. O. Hynes, G. J. Freeman, G. Kroemer, L. Zitvogel, R. Weissleder, M. J. Pittet, Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy. Immunity 44, 343-354 (2016).
23. E. B. Golden, L. Apetoh, Radiotherapy and immunogenic cell death. Semin Radiat Oncol 25, 11-17 (2015).
24. R. W. Jenkins, D. A. Barbie, K. T. Flaherty, Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer 118, 9-16 (2018).
25. P. Sharma, S. Hu-Lieskovan, J. A. Wargo, A. Ribas, Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell 168, 707-723 (2017).
26. J. M. Michot, C. Bigenwald, S. Champiat, M. Collins, F. Carbonnel, S. Postel-Vinay, A. Berdelou, A. Varga, R. Bahleda, A. Hollebecque, C. Massard, A. Fuerea, V. Ribrag, A. Gazzah, J. P. Armand, N. Amellal, E. Angevin, N. Noel, C. Boutros, C. Mateus, C. Robert, J. C. Soria, A. Marabelle, O. Lambotte, Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 54, 139-148 (2016).
27. F. Madeo, T. Eisenberg, F. Pietrocola, G. Kroemer, Spermidine in health and disease. Science 359, (2018).
28. T. Eisenberg, M. Abdellatif, S. Schroeder, U. Primessnig, S. Stekovic, T. Pendl, A. Harger, J. Schipke, A. Zimmermann, A. Schmidt, M. Tong, C. Ruckenstuhl, C. Dammbrueck, A. S. Gross, V. Herbst, C. Magnes, G. Trausinger, S. Narath, A. Meinitzer, Z. Hu, A. Kirsch, K. Eller, D. Carmona-Gutierrez, S. Buttner, F. Pietrocola, O. Knittelfelder, E. Schrepfer, P. Rockenfeller, C. Simonini, A. Rahn, M. Horsch, K. Moreth, J. Beckers, H. Fuchs, V. Gailus-Durner, F. Neff, D. Janik, B. Rathkolb, J. Rozman, M. H. de Angelis, T. Moustafa, G. Haemmerle, M. Mayr, P. Willeit, M. von Frieling-Salewsky, B. Pieske, L. Scorrano, T. Pieber, R. Pechlaner, J. Willeit, S. J. Sigrist, W. A. Linke, C. Muhlfeld, J. Sadoshima, J. Dengjel, S. Kiechl, G. Kroemer, S. Sedej, F. Madeo, Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med 22, 1428-1438 (2016).
Claims (15)
- それを必要とする患者の癌を治療する方法であって、化学療法及び免疫チェックポイント阻害剤とカロリー制限模倣物の治療的に有効な組み合わせを前記患者に投与することを含む、方法。
- ミトコンドリアピルビン酸担体複合体(MPC)の阻害剤、ミトコンドリアカルニチンパルミチン酸転移酵素−1(CTP1)の阻害剤、ミトコンドリアクエン酸担体(CiC)の阻害剤、ATP−クエン酸リアーゼ(ACLY)の阻害剤、EP300アセチルトランスフェラーゼ阻害剤、及びアシル−CoA合成酵素短鎖ファミリーメンバー2(ACCS2)の阻害剤からなる群から選択される、請求項1に記載の方法。
- 前記カロリー制限模倣物が、ヒドロキシクエン酸、リポ酸、スペルミジン及びそれらの混合物からなる群から選択される、請求項1又は2に記載の方法。
- 前記カロリー制限模倣物がヒドロキシクエン酸である、請求項1〜3のいずれか一項に記載の方法。
- 前記カロリー制限模倣物がリポ酸に関連付けられるヒドロキシクエン酸である、請求項1〜3のいずれか一項に記載の方法。
- 前記化学療法が、チオテパ及びシクロスホスファミドなどのアルキル化剤;ブスルファン、インプロスルファン及びピポスルファンなどのアルキルスルホン酸塩;ベンゾドーパ、カルボコン、メツレドーパ、及びウレドーパなどのアジリジン類;アルトレタミン、トリエチレンメラミン、トリエチレンホスホラミド、トリエチレンチオホスホラミド及びトリメチロールメラミンを含むエチレンイミン類及びメチルアメラミン類;アセトゲニン類(特に、ブラタシン及びブラタシノン);カンプトテシン(合成類似体トポテカンを含む);ブリオスタチン;カリスタチン;CC−1065(そのアドゼレシン、カルゼレシン及びビゼレシン合成類似体を含む);クリプトフィシン類(特に、クリプトフィシン1及びクリプトフィシン8);ドラスタチン;デュオカルマイシン(合成類似体KW−2189及びCB1−TM1を含む);エレウテロビン;パンクラチスタチン;サルコジクチン;スポンジスタチン;クロラムブシル、クロロナファジン、クロロホスファミド、エストラムスチン、イホスファミド、メクロレタミン、メクロレタミンオキシド塩酸塩、メルファラン、ノベンビチン、フェネステリン、プレドニムスチン、トロホスファミド、ウラシルマスタードなどのナイトロジェンマスタード;カルムスチン、クロロゾトシン、フォテムスチン、ロムスチン、ニムスチン、及びラニムスチンなどのニトロソウレア;エンジイン抗生物質(例えば、カリケアマイシン、特にカリケアマイシンガンマII及びカリケアマイシンオメガII)などの抗生物質;ダイネミシンAを含むダイネミシン;クロドロネートなどのビスホスホネート類;エスペラミシン;並びにネオカルジノスタチンクロモフォア及び関連クロモプロテインエンジイン抗生物質クロモフォア、アクラシノマイシン類、アクチノマイシン、オースラルナイシン、アザセリン、ブレオマイシン類、カクチノマイシン、カラビシン、カミノマイシン、カルジノフィリン、クロモマイシン類、ダクチノマイシン、ダウノルビシン、デトルビシン、6−ジアゾ−5−オキソ−L−ノルロイシン、ドキソルビシン(モルホリノドキソルビシン、シアノモルホリノドキソルビシン、2−ピロリノ−ドキソルビシン及びデオキシドキソルビシンを含む)、エピルビシン、エソルビシン、イダルビシン、マルセロマイシン、マイトマイシンCなどのマイトマイシン類、ミコフェノール酸、ノガラマイシン、オリボマイシン類、ペプロマイシン、ポルフィロマイシン、ピューロマイシン、ケラマイシン(quelamycin)、ロドルビシン、ストレプトニグリン、ストレプトゾシン、ツベルシジン、ウベニメックス、ジノスタチン、ゾルビシン;メトトレキサート及び5−フルオロウラシル(5−FU)などの抗代謝拮抗薬;デノプテリン、メトトレキサート、プテロプテリン、トリメトレキサートなどの葉酸類似体;フルダラビン、6−メルカプトプリン、チアミプリン、チオグアニンなどのプリン類似体;アンシタビン、アザシチジン、6−アザウリジン、カルモフール、シタラビン、ジデオキシウリジン、ドキシフルリジン、エノシタビン、フロクスウリジンなどのピリミジン類似体;カルステロン、プロピオン酸ドロモスタノロン、エピチオスタノール、メピチオスタン、テストラクトンなどのアンドロゲン類;アミノグルテチミド、ミトタン、トリロスタンなどの抗副腎剤類;フロリン酸(frolinic acid)などの葉酸補充剤;アセグラトン;アルドホスファミドグリコシド;アミノレブリン酸;エニルウラシル;アムサクリン;ベストラブシル;ビサントレン;エダトラキサート(edatraxate);デフォファミン(defofamine);デメコルシン;ジアジコン;エルフォルミチン(elformithine);酢酸エリプチニウム;エポチロン;エトグルシド;硝酸ガリウム;ヒドロキシウレア;レンチナン;ロニダイニン(lonidainine);メイタンシンなどのメイタンシノイド類及びアンサマイトシン類;ミトグアゾン;ミトキサントロン;モピダンモール(mopidanmol);ニトラエリン(nitraerine);ペントスタチン;フェナメト(phenamet);ピラルビシン;ロソキサントロン;ポドフィリン酸;2−エチルヒドラジド;プロカルバジン;PSK多糖複合体;ラゾキサン;リゾキシン;シゾフラン;スピロゲルマニウム;テヌアゾン酸;トリアジコン;2,2’,2’’−トリクロロトリエチルアミン;トリコテセン類(特に、T−2毒素、ベラキュリン(verracurin)A、ロリジンA及びアングイジン);ウレタン;ビンデシン;ダカルバジン;マンノムスチン;ミトブロニトール;ミトラクトール;ピポブロマン;ガシトシン;アラビノシド(「Ara−C」);シクロホスファミド;チオテパ;タキソイド類、例えば、パクリタキセル及びドセタキセル;クロラムブシル;ゲムシタビン;6−チオグアニン;メルカプトプリン;メトトレキサート;シスプラチン、オキサリプラチン、及びカルボプラチンなどの白金配位錯体;ビンブラスチン;白金;エトポシド(VP‐16);イホスファミド;ミトキサントロン;ビンクリスチン;ビノレルビン;ノバントロン;テニポシド;エダトレキサート;ダウノマイシン;アミノプテリン;ゼローダ;イバンドロネート;イリノテカン(例えば、CPT‐11);トポイソメラーゼ阻害剤RFS2000;ジフルオロメチルオルニチン(DMFO);レチノイン酸などのレチノイド類;カペシタビン;並びに上記のいずれかの医薬として許容される塩、酸又は誘導体からなる群から選択される治療有効量の化学療法剤を前記患者に投与することからなる、請求項1〜5のいずれか一項に記載の方法。
- 前記化学療法は、シクロスホスファミド、ドラスタチン、パンクラチスタチン、メクロレタミン、ブレオマイシン類、ダクチノマイシン、ダウノルビシン、ドキソルビシン、モルホリノドキソルビシン、シアノモルホリノドキソルビシン、2−ピロリノドキソルビシン、デオキシドキソルビシン、エピルビシン、イダルビシン、5−フルオロウラシル、トリメトレキサート、エポチロン類、ロニダミン、メイタンシン、ミトキサントロン、PSK多糖複合体、ベルカリンA、ビンデシン、シトシンアラビノシド、パクリタキセル、nab−パクリタキセル、ドセタキセル、6−チオグアニン、シスプラチン、オキサリプラチン、カルボプラチン、ビンブラスチン、白金、アンサミトシン類、ビンクリスチン、ビノレルビン、ノバントロン(ミトキサントロン)、ダウノマイシン、イリノテカン、レチノイン酸、ボルテゾミブ、ジギトキシン、ジゴキシン、パツピロン、ヒペリシン、セツキシマブ、セプタシジン、ヘダマイシン、CDDP、マイトマイシンC、テモゾロミド及びペメトレキセドから選択される治療有効量の化学療法剤を前記患者に投与することからなる、請求項1〜5のいずれか一項に記載の方法。
- 前記免疫チェックポイント阻害剤が、PD−1アンタゴニスト、PD−L1アンタゴニスト、PD−L2アンタゴニスト、CTLA−4アンタゴニスト、VISTAアンタゴニスト、TIM−3アンタゴニスト、LAG−3アンタゴニスト、IDOアンタゴニスト、KIR2Dアンタゴニスト、A2ARアンタゴニスト、B7−H3アンタゴニスト、B7−H4アンタゴニスト、及びBTLAアンタゴニストからなる群から選択される、請求項1〜7のいずれか一項に記載の方法。
- 前記免疫チェックポイント阻害剤が、PD−1アンタゴニストとCTLA−4アンタゴニストの治療上有効な組み合わせである、請求項1〜8のいずれか一項に記載の方法。
- 前記免疫チェックポイント阻害剤が、ニボルマブ、ペンブロリズマブ、ピディリズマブ、アベルマブ、デュルバルマブ、アテゾリムマブ、イピリムマブ及びトレメリムマブからなる群から選択される、請求項1〜9のいずれか一項に記載の方法。
- −前記少なくとも1つのカロリー制限模倣物が、ヒドロキシクエン酸又はリポ酸に関連付けられるヒドロキシクエン酸である;
−前記化学療法が、シスプラチン、オキサリプラチン及びカルボプラチンから選択される化学療法剤;パクリタキセル、nab−パクリタキセル、ドセタキセル及びタキソテールから選択されるタキサン類;ビンデシン、ビンブラスチン、ビンクリスチン及びビノレルビンから選択されるビンカアルカロイド類;ミトキサントロン、ダウノルビシン、ドキソルビシン、エピルビシン、イダルビシン、バルルビシン及びジトリサルビシンから選択されるアントラサイクリン類;ゲムシタビン;ペメトレキセド;それらの混合物及びそれらの医薬として許容される塩である;かつ
−前記免疫チェックポイント阻害剤が、ニボルマブ、ペンブロリズマブ、ピディリズマブ、アベルマブ、デュルバルマブ、アテゾリムマブ、イピリムマブ及びトレメリムマブからなる群から選択される、
請求項1〜10のいずれか一項に記載の方法。 - −前記少なくとも1つのカロリー制限模倣物が、ヒドロキシクエン酸又はリポ酸に関連付けられるヒドロキシクエン酸である;
−前記化学療法が、シスプラチン、オキサリプラチン及びカルボプラチンから選択される化学療法剤;カルボプラチン及びペメトレキセドの同時若しくは逐次的な投与、又はオキサリプラチン及び5−FUの同時若しくは逐次投与;パクリタキセル、nab−パクリタキセル、ドセタキセル及びタキソテールから選択されるタキサン類;ゲムシタビン、ペメトレキセド、ミトキサントロン;並びにそれらの混合物及びそれらの医薬として許容される塩である;かつ
−前記免疫チェックポイント阻害剤が、ニボルマブ、ペンブロリズマブ、ピディリズマブ、アベルマブ、デュルバルマブ、アテゾリムマブ、イピリムマブ及びトレメリムマブからなる群から選択される、請求項1〜10のいずれか一項に記載の方法。 - 前記免疫チェックポイント阻害剤が、化学療法及び/又は免疫チェックポイント阻害剤と同時に投与される、請求項1〜10のいずれか一項に記載の方法。
- 前記免疫チェックポイント阻害剤が、化学療法及び/又は免疫チェックポイント阻害剤の前に投与される、請求項1〜10のいずれか一項に記載の方法。
- 前記患者が、悪性の新生物、癌腫、未分化癌腫、巨細胞癌及び紡錘細胞癌、小細胞癌、乳頭癌、扁平上皮癌、リンパ上皮癌、基底細胞癌、石灰化上皮腫、移行上皮癌、乳頭移行上皮癌、腺癌、悪性の胃腸癌、胆管癌、肝細胞癌、複合肝細胞癌及び胆管癌、小柱腺癌、腺様嚢胞癌、腺腫性ポリープ中の腺癌、家族性大腸ポリポーシスの腺癌、固形癌、悪性のカルチノイド腫瘍、細気管支肺胞腺癌、乳頭腺癌、色素嫌性癌、好酸性癌、好酸性腺癌、好塩基性癌、明細胞腺癌、顆粒細胞癌、濾胞腺癌、乳頭腺癌及び濾胞腺癌、非被包性硬化性癌(nonencapsulating sclerosing carcinoma)、副腎皮質癌、類内膜癌、皮膚付属器癌、アポクリン腺癌、脂腺癌、耳垢腺癌、粘膜表皮癌、嚢胞腺癌、乳頭状嚢腺癌、乳頭状漿液性嚢胞腺癌、粘液性嚢胞腺癌、粘液性腺癌、印環細胞癌、浸潤性腺管癌、髄様癌、小葉癌、炎症性癌、乳房のパジェット病、腺房細胞癌、腺扁平上皮癌、扁平上皮化生を伴う腺癌、悪性胸腺腫、悪性卵巣間質性腫瘍、悪性莢膜細胞腫、悪性顆粒膜細胞腫、悪性アンドロブラストーマ、セルトリ細胞癌、悪性ライディッヒ細胞腫、悪性脂質細胞腫、悪性傍神経節腫、悪性乳房外傍神経節腫、褐色細胞腫、血管球血管肉腫、悪性黒色腫、無色素性黒色腫、表在拡大型黒色腫、巨大色素性母斑中の悪性黒色腫、類上皮細胞黒色腫、悪性青色母斑、肉腫、線維肉腫、悪性線維性組織球腫、粘液肉腫、脂肪肉腫、平滑筋肉腫、横紋筋肉腫、胎児性横紋筋肉腫、胞巣状横紋筋肉腫、間質性肉腫、悪性混合腫瘍、ミュラー管混合腫瘍、腎芽腫、肝芽腫、癌肉腫、悪性間葉腫、悪性ブレンナー腫瘍、悪性葉状腫瘍、滑膜肉腫、悪性中皮腫、未分化胚細胞腫、胚性癌腫、悪性奇形腫、悪性卵巣甲状腺腫、絨毛癌、悪性中腎腫、血管肉腫、悪性血管内皮腫、カポジ肉腫、悪性血管内皮腫、リンパ管肉腫、骨肉腫、傍骨性骨肉腫、軟骨肉腫、悪性軟骨芽腫、間葉性軟骨肉腫、骨巨細胞腫、ユーイング肉腫、悪性歯原性腫瘍、エナメル上皮歯牙肉腫、悪性エナメル上皮腫、エナメル上皮線維肉腫、悪性松果体腫、脊索腫、悪性神経膠腫、上衣腫、星状細胞腫、形質性星状細胞腫、線維性星細胞腫、星芽腫、膠芽腫、乏突起膠腫、乏突起膠芽腫、原始神経外胚葉性、小脳肉腫、神経節神経芽腫、神経芽腫、網膜芽細胞腫、嗅神経腫瘍、悪性髄膜腫、神経線維肉腫、悪性神経線維鞘腫、悪性顆粒細胞腫、悪性リンパ腫、ホジキン病、ホジキンリンパ腫、側肉芽腫、悪性リンパ腫、小リンパ球性、悪性リンパ腫、びまん性大細胞型、濾胞性悪性リンパ腫、菌状息肉症、その他の特定されている非ホジキンリンパ腫、悪性組織球症、多発性骨髄腫、マスト細胞肉腫、免疫増殖性小腸疾患、白血病、リンパ性白血病、形質細胞性白血病、赤白血病、リンパ肉腫細胞白血病、骨髄性白血病、好塩基球性白血病、好酸球性白血病、単球性白血病、肥満細胞性白血病、巨核芽球性白血病、骨髄肉腫、及び毛髪様細胞白血病を患っている、請求項1に記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18305257.0 | 2018-03-12 | ||
EP18305257 | 2018-03-12 | ||
EP18305359 | 2018-03-29 | ||
EP18305359.4 | 2018-03-29 | ||
PCT/EP2019/056041 WO2019175113A1 (en) | 2018-03-12 | 2019-03-11 | Use of caloric restriction mimetics for potentiating chemo-immunotherapy for the treatment of cancers |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021517589A true JP2021517589A (ja) | 2021-07-26 |
JPWO2019175113A5 JPWO2019175113A5 (ja) | 2022-03-10 |
Family
ID=66102028
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020572608A Pending JP2021517589A (ja) | 2018-03-12 | 2019-03-11 | 癌の治療のための化学免疫療法を増強するためのカロリー制限模倣物の使用 |
Country Status (11)
Country | Link |
---|---|
US (1) | US20210030703A1 (ja) |
EP (1) | EP3765085A1 (ja) |
JP (1) | JP2021517589A (ja) |
KR (1) | KR20210004966A (ja) |
CN (1) | CN112218658A (ja) |
AU (1) | AU2019236402A1 (ja) |
BR (1) | BR112020018585A8 (ja) |
CA (1) | CA3093742A1 (ja) |
RU (1) | RU2020133451A (ja) |
SG (1) | SG11202008696RA (ja) |
WO (1) | WO2019175113A1 (ja) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220401385A1 (en) * | 2019-11-13 | 2022-12-22 | Kyoto University | Combination Therapy Based on PD-1 Signaling Inhibitors |
IT202000007153A1 (it) * | 2020-04-03 | 2021-10-03 | Ifom Fondazione St Firc Di Oncologia Molecolare | Apporto calorico ridotto e immunoterapia per il trattamento del cancro |
AU2022280511A1 (en) * | 2021-05-28 | 2023-12-14 | Nippon Kayaku Kabushiki Kaisha | Combined use of ubenimex and immune checkpoint inhibitor |
WO2023288299A1 (en) * | 2021-07-15 | 2023-01-19 | Farber Partners, Llc | Use of methanol and prodrugs thereof in therapy |
CN115590187A (zh) * | 2021-10-08 | 2023-01-13 | 南京纽邦生物科技有限公司(Cn) | 通过施用二氢小檗碱模拟热量限制的生物学益处的方法和组合物 |
CN115721659A (zh) * | 2021-12-09 | 2023-03-03 | 苏州百迈生物医药有限公司 | 一种表柔比星复方制剂及其制备方法和应用 |
EP4197525A1 (en) * | 2021-12-20 | 2023-06-21 | Scandion Oncology A/S | Combination of drugs for the treatment of cancer |
CN115531555B (zh) * | 2022-08-19 | 2024-02-09 | 上海市第一人民医院 | 一种甘露糖修饰的纳米颗粒在制备治疗骨肉瘤药物中的应用 |
CN115282147A (zh) * | 2022-08-31 | 2022-11-04 | 深圳市宝安区人民医院 | 罗拉匹坦或/和罗拉匹坦衍生物在抗结核分枝杆菌药物中的应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015049365A2 (en) * | 2013-10-03 | 2015-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating autophagy in a subject in need thereof |
Family Cites Families (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
US5447954A (en) | 1992-05-05 | 1995-09-05 | Smithkline Beecham P.L.C. | Phenylderivate as inhibitors of ATP citrate lyase |
US6051227A (en) | 1995-07-25 | 2000-04-18 | The Regents Of The University Of California, Office Of Technology Transfer | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
US5855887A (en) | 1995-07-25 | 1999-01-05 | The Regents Of The University Of California | Blockade of lymphocyte down-regulation associated with CTLA-4 signaling |
US5811097A (en) | 1995-07-25 | 1998-09-22 | The Regents Of The University Of California | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
JP2001523958A (ja) | 1997-03-21 | 2001-11-27 | ブライハム アンド ウィミンズ ホスピタル,インコーポレイテッド | 免疫療法のctla−4結合ペプチド |
US7109003B2 (en) | 1998-12-23 | 2006-09-19 | Abgenix, Inc. | Methods for expressing and recovering human monoclonal antibodies to CTLA-4 |
KR100856446B1 (ko) | 1998-12-23 | 2008-09-04 | 화이자 인크. | Ctla-4에 대한 인간 단일클론 항체 |
US6682736B1 (en) | 1998-12-23 | 2004-01-27 | Abgenix, Inc. | Human monoclonal antibodies to CTLA-4 |
EP2829609A1 (en) | 1999-08-24 | 2015-01-28 | E. R. Squibb & Sons, L.L.C. | Human CTLA-4 antibodies and their uses |
US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
US6414002B1 (en) | 1999-09-22 | 2002-07-02 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
AU2001233027A1 (en) | 2000-01-27 | 2001-08-07 | Genetics Institute, Llc | Antibodies against ctla4 (cd152), conjugates comprising same, and uses thereof |
US7219016B2 (en) | 2001-04-20 | 2007-05-15 | Yale University | Systems and methods for automated analysis of cells and tissues |
SI1558648T1 (sl) | 2002-10-17 | 2012-05-31 | Genmab As | Človeška monoklonalna protitelesa proti CD |
UA80767C2 (en) | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
GB0229734D0 (en) | 2002-12-23 | 2003-01-29 | Qinetiq Ltd | Grading oestrogen and progesterone receptors expression |
JP4511943B2 (ja) | 2002-12-23 | 2010-07-28 | ワイス エルエルシー | Pd−1に対する抗体およびその使用 |
US7257268B2 (en) | 2003-02-28 | 2007-08-14 | Aperio Technologies, Inc. | Systems and methods for image pattern recognition |
LT2439273T (lt) | 2005-05-09 | 2019-05-10 | Ono Pharmaceutical Co., Ltd. | Žmogaus monokloniniai antikūnai prieš programuotos mirties 1(pd-1) baltymą, ir vėžio gydymo būdai, naudojant vien tik anti-pd-1 antikūnus arba derinyje su kitais imunoterapiniais vaistais |
CN105330741B (zh) | 2005-07-01 | 2023-01-31 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
DK2134689T3 (da) | 2007-03-16 | 2014-06-30 | Scripps Research Inst | Inhibitorer af fokal adhæsionskinase |
MX2009011090A (es) | 2007-04-18 | 2009-11-02 | Pfizer Prod Inc | Derivados de sulfonil amida para el tratamiento del crecimiento celular anormal. |
US8023714B2 (en) | 2007-06-06 | 2011-09-20 | Aperio Technologies, Inc. | System and method for assessing image interpretability in anatomic pathology |
BRPI0907718A2 (pt) | 2008-02-11 | 2017-06-13 | Curetech Ltd | método para tratar um tumor, método para melhorar a tolerabilidade a pelo menos um agente quimiterápico, método para aumentar a sobrevida de um indivíduo que tem um tumor, método para reduzir ou prevenir recidiva tumoral, uso de um anticorpo monoclonal humanizado ou seu fragmento e anticorpo monoclonal humanizado ou seu fragmento |
EP2249650A4 (en) | 2008-02-19 | 2012-01-11 | Glaxosmithkline Llc | ANILINOPYRIDINE AS A FAK HEMMER |
EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
JP5551689B2 (ja) | 2008-06-17 | 2014-07-16 | アストラゼネカ アクチボラグ | ピリジン化合物 |
US20110159023A1 (en) | 2008-08-25 | 2011-06-30 | Solomon Langermann | Pd-1 antagonists and methods for treating infectious disease |
NZ591130A (en) | 2008-08-25 | 2012-09-28 | Amplimmune Inc | Compositions comprising a PD-1 antagonists and cyclophosphamide and methods of use thereof |
US9240043B2 (en) | 2008-09-16 | 2016-01-19 | Novartis Ag | Reproducible quantification of biomarker expression |
US20140155410A1 (en) | 2008-10-27 | 2014-06-05 | Glaxosmithkline Llc | Pyrazolylaminopyridines as inhibitors of fak |
JO3067B1 (ar) | 2008-10-27 | 2017-03-15 | Glaxosmithkline Llc | بيرميدينات بيرازولو امينو كمثبطات ل fak |
US20100120727A1 (en) * | 2008-11-12 | 2010-05-13 | Kyphia Pharmaceuticals, Inc. | Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof |
SI2376535T1 (sl) | 2008-12-09 | 2017-07-31 | F. Hoffmann-La Roche Ag | Protitelesa anti-pd-l1 in njihova uporaba za izboljšanje funkcije celic t |
EP2417984B1 (en) | 2009-04-10 | 2016-03-30 | Kyowa Hakko Kirin Co., Ltd. | Method for treatment of blood tumor using anti-tim-3 antibody |
US8345509B2 (en) | 2009-04-16 | 2013-01-01 | Chevron U.S.A., Inc. | System and method to create three-dimensional images of non-linear acoustic properties in a region remote from a borehole |
US20110111435A1 (en) | 2009-11-06 | 2011-05-12 | SlidePath Limited | Detecting Cell Surface Markers |
JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Pd−l1/pd−l2の同時阻害 |
NZ599405A (en) | 2009-11-24 | 2014-09-26 | Medimmune Ltd | Targeted binding agents against b7-h1 |
TR201807750T4 (tr) | 2010-06-11 | 2018-06-21 | Kyowa Hakko Kirin Co Ltd | Anti-TIM-3 antikoru. |
CN103339235B (zh) | 2011-01-25 | 2015-02-11 | 国际壳牌研究有限公司 | 气化反应器 |
WO2013006490A2 (en) | 2011-07-01 | 2013-01-10 | Cellerant Therapeutics, Inc. | Antibodies that specifically bind to tim3 |
KR101981873B1 (ko) | 2011-11-28 | 2019-05-23 | 메르크 파텐트 게엠베하 | 항-pd-l1 항체 및 그의 용도 |
LT2970155T (lt) | 2013-03-15 | 2018-06-25 | Bristol-Myers Squibb Company | Indolamino 2,3-dioksigenazės (ido) inhibitoriai |
PL3041827T3 (pl) | 2013-09-06 | 2018-09-28 | Aurigene Discovery Tech Limited | Pochodne 1,2,4-oksadiazolu jako immunomodulatory |
PL3041828T3 (pl) | 2013-09-06 | 2018-10-31 | Aurigene Discovery Technologies Limited | Pochodne 1,3,4-oksadiazolu i 1,3,4-tiadiazolu jako immunomodulatory |
WO2017004192A1 (en) * | 2015-06-29 | 2017-01-05 | Verastem, Inc. | Therapeutic compositions, combinations, and methods of use |
-
2019
- 2019-03-11 JP JP2020572608A patent/JP2021517589A/ja active Pending
- 2019-03-11 SG SG11202008696RA patent/SG11202008696RA/en unknown
- 2019-03-11 BR BR112020018585A patent/BR112020018585A8/pt unknown
- 2019-03-11 CN CN201980031861.7A patent/CN112218658A/zh active Pending
- 2019-03-11 US US16/980,003 patent/US20210030703A1/en active Pending
- 2019-03-11 RU RU2020133451A patent/RU2020133451A/ru unknown
- 2019-03-11 KR KR1020207028067A patent/KR20210004966A/ko unknown
- 2019-03-11 AU AU2019236402A patent/AU2019236402A1/en active Pending
- 2019-03-11 CA CA3093742A patent/CA3093742A1/en active Pending
- 2019-03-11 EP EP19716299.3A patent/EP3765085A1/en active Pending
- 2019-03-11 WO PCT/EP2019/056041 patent/WO2019175113A1/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015049365A2 (en) * | 2013-10-03 | 2015-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating autophagy in a subject in need thereof |
Non-Patent Citations (3)
Title |
---|
CANCER CELL, vol. 30, no. 1, JPN6023012307, 2016, pages 147 - 160, ISSN: 0005022158 * |
CANCER IMMUNOLOGY, vol. 63, no. 6, JPN6023012306, 2014, pages 615 - 626, ISSN: 0005022159 * |
SEMINARS IN CANCER BIOLOGY, vol. 43, JPN6023012305, 2017, pages 134 - 138, ISSN: 0005022160 * |
Also Published As
Publication number | Publication date |
---|---|
EP3765085A1 (en) | 2021-01-20 |
BR112020018585A8 (pt) | 2022-12-06 |
KR20210004966A (ko) | 2021-01-13 |
WO2019175113A1 (en) | 2019-09-19 |
CN112218658A (zh) | 2021-01-12 |
RU2020133451A (ru) | 2022-04-12 |
SG11202008696RA (en) | 2020-10-29 |
CA3093742A1 (en) | 2019-09-19 |
US20210030703A1 (en) | 2021-02-04 |
BR112020018585A2 (pt) | 2020-12-29 |
AU2019236402A1 (en) | 2020-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2021517589A (ja) | 癌の治療のための化学免疫療法を増強するためのカロリー制限模倣物の使用 | |
JP6464085B2 (ja) | 神経膠芽腫の治療のための併用療法 | |
JP2016530280A (ja) | 膠芽腫治療のための併用療法 | |
JP6764017B2 (ja) | がんの処置での使用のためのコビシスタット | |
KR102082363B1 (ko) | 난소암의 치료를 위한 조합 치료 | |
US20130217710A1 (en) | Methods for treating cancer | |
JP6976941B2 (ja) | 白血病に罹患している対象の治療レジメンを選択するためのアッセイ及び方法 | |
JP2020517629A5 (ja) | ||
TW202003553A (zh) | 用於治療癌症之abbv-621與抗癌劑之組合 | |
US20210128609A1 (en) | Oncology treatments using zinc agents | |
TWI663974B (zh) | 以法呢基轉移酶(farnesyltransferase)抑制劑治療癌症之方法 | |
US20230121867A1 (en) | Compositions and methods for treating diseases and conditions by depletion of mitochondrial or genomic dna from circulation | |
TW202241455A (zh) | 使用akr1c3活化化合物與免疫檢查點抑制劑之組合療法 | |
US20230331849A1 (en) | CpG IMMUNOCONJUGATES FOR CANCER THERAPY | |
US20220025036A1 (en) | Use of il-1beta binding antibodies | |
US20210315878A1 (en) | Compositions and methods for reducing cancer stem cells | |
Powell et al. | P01. 13 MERTK signaling is critical for T cell proliferation and memory | |
WO2015127227A1 (en) | Uses of flagellin for improved chemotherapy | |
WO2024030659A1 (en) | An hdac inhibitor for treating cancer with a modified stk11 activity or expression | |
Foley et al. | A Phase I Study of Romidepsin in Combination with Gemcitabine, Oxaliplatin, and Dexamethasone in Patients with Relapsed or Refractory Aggressive Lymphomas Enriched for T-Cell Lymphomas |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220228 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220228 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230328 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230627 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20230629 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230926 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20231219 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240325 |