TWI586354B - 布魯頓氏酪胺酸激酶（ｂｒｕｔｏｎ'ｓ ｔｙｒｏｓｉｎｅ ｋｉｎａｓｅ ）抑制劑之組合及其用途 - Google Patents

Info

Publication number

TWI586354B

TWI586354B TW104125847A TW104125847A TWI586354B TW I586354 B TWI586354 B TW I586354B TW 104125847 A TW104125847 A TW 104125847A TW 104125847 A TW104125847 A TW 104125847A TW I586354 B TWI586354 B TW I586354B

Authority

TW

Taiwan

Prior art keywords

inhibitor

cell

lymphoma

mcl

anticancer agent

Prior art date

2014-08-08

Links

• Espacenet
• Global Dossier
• Discuss

• 229940125814 BTK kinase inhibitor Drugs 0.000 title 1
• 239000003112 inhibitor Substances 0.000 claims description 240
• 239000002246 antineoplastic agent Substances 0.000 claims description 192
• 101000595531 Homo sapiens Serine/threonine-protein kinase pim-1 Proteins 0.000 claims description 175
• 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 claims description 164
• 229940124291 BTK inhibitor Drugs 0.000 claims description 153
• 238000000034 method Methods 0.000 claims description 149
• XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical group 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 claims description 141
• 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 129
• 229960001507 ibrutinib Drugs 0.000 claims description 129
• -1 obobaclax Chemical compound 0.000 claims description 128
• 239000003814 drug Substances 0.000 claims description 124
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 112
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 101
• 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 claims description 98
• 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 claims description 96
• 210000004027 cell Anatomy 0.000 claims description 84
• 206010028980 Neoplasm Diseases 0.000 claims description 76
• 108700026676 Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Proteins 0.000 claims description 72
• 101150113681 MALT1 gene Proteins 0.000 claims description 71
• 210000003719 b-lymphocyte Anatomy 0.000 claims description 71
• 201000011510 cancer Diseases 0.000 claims description 54
• 230000036210 malignancy Effects 0.000 claims description 50
• 206010025323 Lymphomas Diseases 0.000 claims description 48
• 201000010099 disease Diseases 0.000 claims description 41
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
• 229940124597 therapeutic agent Drugs 0.000 claims description 32
• QBKSWRVVCFFDOT-UHFFFAOYSA-N gossypol Chemical compound CC(C)C1=C(O)C(O)=C(C=O)C2=C(O)C(C=3C(O)=C4C(C=O)=C(O)C(O)=C(C4=CC=3C)C(C)C)=C(C)C=C21 QBKSWRVVCFFDOT-UHFFFAOYSA-N 0.000 claims description 30
• MCUJKPPARUPFJM-UWCCDQBKSA-N (5z)-5-[[2-[(3r)-3-aminopiperidin-1-yl]-3-phenylphenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1[C@H](N)CCCN1C(C(=CC=C1)C=2C=CC=CC=2)=C1\C=C/1C(=O)NC(=O)S\1 MCUJKPPARUPFJM-UWCCDQBKSA-N 0.000 claims description 26
• 101001001648 Homo sapiens Serine/threonine-protein kinase pim-2 Proteins 0.000 claims description 26
• 102100036120 Serine/threonine-protein kinase pim-2 Human genes 0.000 claims description 26
• 101001001645 Homo sapiens Serine/threonine-protein kinase pim-3 Proteins 0.000 claims description 23
• 102100036119 Serine/threonine-protein kinase pim-3 Human genes 0.000 claims description 22
• SRQYLNYQAPCPIR-UHFFFAOYSA-N 4-[4-(5,5-dimethyl-4H-thiazol-2-yl)-1-piperazinyl]-6-propylthieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC(CCC)=CC2=C1N(CC1)CCN1C1=NCC(C)(C)S1 SRQYLNYQAPCPIR-UHFFFAOYSA-N 0.000 claims description 21
• 208000003950 B-cell lymphoma Diseases 0.000 claims description 21
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 20
• 208000032839 leukemia Diseases 0.000 claims description 20
• 230000003211 malignant effect Effects 0.000 claims description 20
• GZLNOSRHZLTDMT-UHFFFAOYSA-N 2-(n-[2-(benzimidazol-1-yl)acetyl]-3-fluoroanilino)-n-cyclopentyl-2-(2-methylphenyl)acetamide Chemical compound CC1=CC=CC=C1C(C(=O)NC1CCCC1)N(C=1C=C(F)C=CC=1)C(=O)CN1C2=CC=CC=C2N=C1 GZLNOSRHZLTDMT-UHFFFAOYSA-N 0.000 claims description 19
• 208000034578 Multiple myelomas Diseases 0.000 claims description 19
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 19
• AATMNHPDEZNXEK-UHFFFAOYSA-N 2-(n-[2-(4-cyanoanilino)acetyl]-3-fluoroanilino)-n-cyclohexyl-2-(2-methylphenyl)acetamide Chemical compound CC1=CC=CC=C1C(C(=O)NC1CCCCC1)N(C=1C=C(F)C=CC=1)C(=O)CNC1=CC=C(C#N)C=C1 AATMNHPDEZNXEK-UHFFFAOYSA-N 0.000 claims description 18
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 18
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 18
• 201000003444 follicular lymphoma Diseases 0.000 claims description 18
• WIJZXSAJMHAVGX-DHLKQENFSA-N ivosidenib Chemical compound FC1=CN=CC(N([C@H](C(=O)NC2CC(F)(F)C2)C=2C(=CC=CC=2)Cl)C(=O)[C@H]2N(C(=O)CC2)C=2N=CC=C(C=2)C#N)=C1 WIJZXSAJMHAVGX-DHLKQENFSA-N 0.000 claims description 18
• FNYGWXSATBUBER-UHFFFAOYSA-N n-cyclohexyl-2-(3-fluoro-n-[2-(2-methylimidazol-1-yl)acetyl]anilino)-2-(2-methylphenyl)acetamide Chemical compound CC1=NC=CN1CC(=O)N(C=1C=C(F)C=CC=1)C(C=1C(=CC=CC=1)C)C(=O)NC1CCCCC1 FNYGWXSATBUBER-UHFFFAOYSA-N 0.000 claims description 18
• CBHCDHNUZWWAPP-UHFFFAOYSA-N pecazine Chemical compound C1N(C)CCCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 CBHCDHNUZWWAPP-UHFFFAOYSA-N 0.000 claims description 18
• 229950007538 pecazine Drugs 0.000 claims description 18
• 201000006037 primary mediastinal B-cell lymphoma Diseases 0.000 claims description 18
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 17
• ZGUGWUXLJSTTMA-UHFFFAOYSA-N Promazinum Chemical compound C1=CC=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZGUGWUXLJSTTMA-UHFFFAOYSA-N 0.000 claims description 17
• KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 claims description 17
• 229960003598 promazine Drugs 0.000 claims description 17
• 229960002784 thioridazine Drugs 0.000 claims description 17
• 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 16
• TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 claims description 16
• RAYNZUHYMMLQQA-ZEQRLZLVSA-N 2,3,5-trihydroxy-7-methyl-n-[(2r)-2-phenylpropyl]-6-[1,6,7-trihydroxy-3-methyl-5-[[(2r)-2-phenylpropyl]carbamoyl]naphthalen-2-yl]naphthalene-1-carboxamide Chemical compound C1([C@@H](C)CNC(=O)C=2C3=CC(C)=C(C(=C3C=C(O)C=2O)O)C=2C(O)=C3C=C(O)C(O)=C(C3=CC=2C)C(=O)NC[C@H](C)C=2C=CC=CC=2)=CC=CC=C1 RAYNZUHYMMLQQA-ZEQRLZLVSA-N 0.000 claims description 15
• 101150054675 MIM1 gene Proteins 0.000 claims description 15
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 15
• QHOPXUFELLHKAS-UHFFFAOYSA-N Thespesin Natural products CC(C)c1c(O)c(O)c2C(O)Oc3c(c(C)cc1c23)-c1c2OC(O)c3c(O)c(O)c(C(C)C)c(cc1C)c23 QHOPXUFELLHKAS-UHFFFAOYSA-N 0.000 claims description 15
• 229940127089 cytotoxic agent Drugs 0.000 claims description 15
• 229930000755 gossypol Natural products 0.000 claims description 15
• 229950005277 gossypol Drugs 0.000 claims description 15
• 201000011649 lymphoblastic lymphoma Diseases 0.000 claims description 15
• MHXGEROHKGDZGO-UHFFFAOYSA-N N-[(1-methyl-4-piperidinyl)methyl]-3-[3-(trifluoromethoxy)phenyl]-6-imidazo[1,2-b]pyridazinamine Chemical compound C1CN(C)CCC1CNC1=NN2C(C=3C=C(OC(F)(F)F)C=CC=3)=CN=C2C=C1 MHXGEROHKGDZGO-UHFFFAOYSA-N 0.000 claims description 13
• 108091049902 miR-33a stem-loop Proteins 0.000 claims description 13
• VRQXRVAKPDCRCI-ZNMIVQPWSA-N n-[4-[(1r,3s,5s)-3-amino-5-methylcyclohexyl]pyridin-3-yl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide Chemical compound C1[C@H](C)C[C@H](N)C[C@@H]1C1=CC=NC=C1NC(=O)C1=CC=C(F)C(C=2C(=CC=CC=2F)F)=N1 VRQXRVAKPDCRCI-ZNMIVQPWSA-N 0.000 claims description 13
• 230000002195 synergetic effect Effects 0.000 claims description 13
• 230000001225 therapeutic effect Effects 0.000 claims description 13
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 12
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 12
• 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 11
• 229960003668 docetaxel Drugs 0.000 claims description 11
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 10
• 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims description 10
• 208000021937 marginal zone lymphoma Diseases 0.000 claims description 10
• 201000006845 reticulosarcoma Diseases 0.000 claims description 10
• 208000029922 reticulum cell sarcoma Diseases 0.000 claims description 10
• 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 claims description 9
• 208000011691 Burkitt lymphomas Diseases 0.000 claims description 9
• 208000007452 Plasmacytoma Diseases 0.000 claims description 9
• 229960001467 bortezomib Drugs 0.000 claims description 9
• 229960000390 fludarabine Drugs 0.000 claims description 9
• 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 claims description 9
• 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 claims description 9
• 210000001541 thymus gland Anatomy 0.000 claims description 9
• UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 claims description 8
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 8
• 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 claims description 8
• 201000003791 MALT lymphoma Diseases 0.000 claims description 8
• 229930012538 Paclitaxel Natural products 0.000 claims description 8
• 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 claims description 8
• 230000001154 acute effect Effects 0.000 claims description 8
• 229960004630 chlorambucil Drugs 0.000 claims description 8
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 8
• 229960004679 doxorubicin Drugs 0.000 claims description 8
• 229960005167 everolimus Drugs 0.000 claims description 8
• 229960003445 idelalisib Drugs 0.000 claims description 8
• 229960001101 ifosfamide Drugs 0.000 claims description 8
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 8
• 229960004942 lenalidomide Drugs 0.000 claims description 8
• GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims description 8
• 229960002450 ofatumumab Drugs 0.000 claims description 8
• 229960001592 paclitaxel Drugs 0.000 claims description 8
• 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 8
• 229960004618 prednisone Drugs 0.000 claims description 8
• 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 claims description 8
• 229960004641 rituximab Drugs 0.000 claims description 8
• 210000000952 spleen Anatomy 0.000 claims description 8
• 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 8
• 229960000235 temsirolimus Drugs 0.000 claims description 8
• 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 claims description 8
• 229960003433 thalidomide Drugs 0.000 claims description 8
• 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 7
• 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 claims description 7
• 102100031162 Collagen alpha-1(XVIII) chain Human genes 0.000 claims description 7
• 108010079505 Endostatins Proteins 0.000 claims description 7
• 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 claims description 7
• 229960003957 dexamethasone Drugs 0.000 claims description 7
• 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 claims description 7
• 229950005309 fostamatinib Drugs 0.000 claims description 7
• GKDRMWXFWHEQQT-UHFFFAOYSA-N fostamatinib Chemical compound 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 GKDRMWXFWHEQQT-UHFFFAOYSA-N 0.000 claims description 7
• 208000026876 intravascular large B-cell lymphoma Diseases 0.000 claims description 7
• 210000001370 mediastinum Anatomy 0.000 claims description 7
• KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 claims description 7
• 229960004963 mesalazine Drugs 0.000 claims description 7
• 229960002340 pentostatin Drugs 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 229960005267 tositumomab Drugs 0.000 claims description 7
• 230000001684 chronic effect Effects 0.000 claims description 6
• 210000002751 lymph Anatomy 0.000 claims description 6
• 239000000203 mixture Substances 0.000 claims description 6
• 206010002412 Angiocentric lymphomas Diseases 0.000 claims description 5
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 5
• 208000006116 lymphomatoid granulomatosis Diseases 0.000 claims description 5
• 239000012528 membrane Substances 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 230000003393 splenic effect Effects 0.000 claims description 4
• 206010036524 Precursor B-lymphoblastic lymphomas Diseases 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 3
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
• 208000028018 Lymphocytic leukaemia Diseases 0.000 claims description 2
• 208000003747 lymphoid leukemia Diseases 0.000 claims description 2
• 101001042041 Bos taurus Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial Proteins 0.000 claims 5
• 101000960234 Homo sapiens Isocitrate dehydrogenase [NADP] cytoplasmic Proteins 0.000 claims 5
• 102100039905 Isocitrate dehydrogenase [NADP] cytoplasmic Human genes 0.000 claims 5
• 102000057613 Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Human genes 0.000 claims 5
• 230000034303 cell budding Effects 0.000 claims 1
• YKLIKGKUANLGSB-HNNXBMFYSA-N idelalisib Chemical compound C1([C@@H](NC=2[C]3N=CN=C3N=CN=2)CC)=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1 YKLIKGKUANLGSB-HNNXBMFYSA-N 0.000 claims 1
• 235000013372 meat Nutrition 0.000 claims 1
• 230000003439 radiotherapeutic effect Effects 0.000 claims 1
• 230000035772 mutation Effects 0.000 description 187
• RRHONYZEMUNMJX-UHFFFAOYSA-N N-[5-[[5-[(4-acetyl-1-piperazinyl)-oxomethyl]-4-methoxy-2-methylphenyl]thio]-2-thiazolyl]-4-[(3-methylbutan-2-ylamino)methyl]benzamide Chemical group C1=C(C(=O)N2CCN(CC2)C(C)=O)C(OC)=CC(C)=C1SC(S1)=CN=C1NC(=O)C1=CC=C(CNC(C)C(C)C)C=C1 RRHONYZEMUNMJX-UHFFFAOYSA-N 0.000 description 153
• 102000012011 Isocitrate Dehydrogenase Human genes 0.000 description 100
• 108010075869 Isocitrate Dehydrogenase Proteins 0.000 description 100
• 101001064870 Homo sapiens Lon protease homolog, mitochondrial Proteins 0.000 description 93
• 102100038732 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 Human genes 0.000 description 70
• 239000000090 biomarker Substances 0.000 description 69
• 238000011282 treatment Methods 0.000 description 67
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 63
• 101150015280 Cel gene Proteins 0.000 description 60
• 108090000623 proteins and genes Proteins 0.000 description 55
• 102100024965 Caspase recruitment domain-containing protein 11 Human genes 0.000 description 51
• 101000761179 Homo sapiens Caspase recruitment domain-containing protein 11 Proteins 0.000 description 51
• 239000000523 sample Substances 0.000 description 51
• 206010066476 Haematological malignancy Diseases 0.000 description 48
• 238000002648 combination therapy Methods 0.000 description 41
• 235000001014 amino acid Nutrition 0.000 description 40
• 101000889732 Homo sapiens Tyrosine-protein kinase Tec Proteins 0.000 description 38
• DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 38
• 102100040177 Tyrosine-protein kinase Tec Human genes 0.000 description 38
• 125000000539 amino acid group Chemical group 0.000 description 35
• 150000001413 amino acids Chemical class 0.000 description 35
• 230000014509 gene expression Effects 0.000 description 35
• 102000004169 proteins and genes Human genes 0.000 description 34
• 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 33
• 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 33
• 238000012544 monitoring process Methods 0.000 description 32
• 235000018102 proteins Nutrition 0.000 description 31
• 229940126656 GS-4224 Drugs 0.000 description 30
• ABSXPNGWJFAPRT-UHFFFAOYSA-N benzenesulfonic acid;n-[3-[[5-fluoro-2-[4-(2-methoxyethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide Chemical compound OS(=O)(=O)C1=CC=CC=C1.C1=CC(OCCOC)=CC=C1NC1=NC=C(F)C(NC=2C=C(NC(=O)C=C)C=CC=2)=N1 ABSXPNGWJFAPRT-UHFFFAOYSA-N 0.000 description 29
• 230000002401 inhibitory effect Effects 0.000 description 29
• 229940122339 MALT1 inhibitor Drugs 0.000 description 28
• 239000004475 Arginine Substances 0.000 description 26
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 26
• 150000007523 nucleic acids Chemical class 0.000 description 25
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 24
• 210000004369 blood Anatomy 0.000 description 23
• 239000008280 blood Substances 0.000 description 23
• TWJGQZBSEMDPQP-UHFFFAOYSA-N 2-chloro-n-[4-[5-(3,4-dichlorophenyl)-3-(2-methoxyethoxy)-1,2,4-triazol-1-yl]phenyl]acetamide Chemical group C=1C=C(NC(=O)CCl)C=CC=1N1N=C(OCCOC)N=C1C1=CC=C(Cl)C(Cl)=C1 TWJGQZBSEMDPQP-UHFFFAOYSA-N 0.000 description 22
• MQGPSCMMNJKMHQ-UHFFFAOYSA-N 7-hydroxyflavone Chemical compound C=1C(O)=CC=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 MQGPSCMMNJKMHQ-UHFFFAOYSA-N 0.000 description 22
• 206010061818 Disease progression Diseases 0.000 description 22
• 230000005750 disease progression Effects 0.000 description 22
• 102000039446 nucleic acids Human genes 0.000 description 22
• 108020004707 nucleic acids Proteins 0.000 description 22
• 108010019421 Janus Kinase 3 Proteins 0.000 description 20
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 20
• 230000027455 binding Effects 0.000 description 19
• 238000011269 treatment regimen Methods 0.000 description 19
• 229940123241 Janus kinase 3 inhibitor Drugs 0.000 description 18
• 102000004422 Phospholipase C gamma Human genes 0.000 description 18
• 108010056751 Phospholipase C gamma Proteins 0.000 description 18
• 230000004048 modification Effects 0.000 description 18
• 238000012986 modification Methods 0.000 description 18
• 150000003839 salts Chemical class 0.000 description 18
• ZHXNIYGJAOPMSO-UHFFFAOYSA-N N-[5-[[5-[(4-acetyl-1-piperazinyl)-oxomethyl]-4-methoxy-2-methylphenyl]thio]-2-thiazolyl]-4-[(3,3-dimethylbutan-2-ylamino)methyl]benzamide Chemical compound C1=C(C(=O)N2CCN(CC2)C(C)=O)C(OC)=CC(C)=C1SC(S1)=CN=C1NC(=O)C1=CC=C(CNC(C)C(C)(C)C)C=C1 ZHXNIYGJAOPMSO-UHFFFAOYSA-N 0.000 description 17
• 239000000427 antigen Substances 0.000 description 17
• JIFCFQDXHMUPGP-UHFFFAOYSA-N 4-tert-butyl-n-[2-methyl-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]benzamide Chemical compound C1=CC=C(C=2N=C(NC=3C=CC(=CC=3)C(=O)N3CCOCC3)C(=O)N(C)C=2)C(C)=C1NC(=O)C1=CC=C(C(C)(C)C)C=C1 JIFCFQDXHMUPGP-UHFFFAOYSA-N 0.000 description 16
• 101001050476 Homo sapiens Tyrosine-protein kinase ITK/TSK Proteins 0.000 description 16
• 102100023345 Tyrosine-protein kinase ITK/TSK Human genes 0.000 description 16
• 101001001642 Xenopus laevis Serine/threonine-protein kinase pim-3 Proteins 0.000 description 16
• 108091007433 antigens Proteins 0.000 description 16
• 102000036639 antigens Human genes 0.000 description 16
• CDOOFZZILLRUQH-GDLZYMKVSA-N n-[3-[6-[4-[(2r)-1,4-dimethyl-3-oxopiperazin-2-yl]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide Chemical compound CN1CCN(C)C(=O)[C@H]1C(C=C1)=CC=C1NC1=NC(C=2C(=C(NC(=O)C=3SC=4CCCCC=4C=3)C=CC=2)C)=CN(C)C1=O CDOOFZZILLRUQH-GDLZYMKVSA-N 0.000 description 16
• 108090000765 processed proteins & peptides Proteins 0.000 description 16
• 230000004083 survival effect Effects 0.000 description 16
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 16
• RNOAOAWBMHREKO-QFIPXVFZSA-N (7S)-2-(4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C(C=C)(=O)N1CCC(CC1)[C@@H]1CCNC=2N1N=C(C=2C(=O)N)C1=CC=C(C=C1)OC1=CC=CC=C1 RNOAOAWBMHREKO-QFIPXVFZSA-N 0.000 description 15
• VVLHQJDAUIPZFH-UHFFFAOYSA-N 4-[4-[[5-fluoro-4-[3-(prop-2-enoylamino)anilino]pyrimidin-2-yl]amino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC=3N=C(NC=4C=C(NC(=O)C=C)C=CC=4)C(F)=CN=3)=CC=2)=C1 VVLHQJDAUIPZFH-UHFFFAOYSA-N 0.000 description 15
• SEJLPXCPMNSRAM-GOSISDBHSA-N 6-amino-9-[(3r)-1-but-2-ynoylpyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one Chemical compound C1N(C(=O)C#CC)CC[C@H]1N1C(=O)N(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C2=C(N)N=CN=C21 SEJLPXCPMNSRAM-GOSISDBHSA-N 0.000 description 15
• BSSBAJKNZOHHCA-UHFFFAOYSA-N 7-benzyl-1-(3-piperidin-1-ylpropyl)-2-(4-pyridin-4-ylphenyl)-5h-imidazo[4,5-g]quinoxalin-6-one Chemical compound C1CCCCN1CCCN1C=2C=C3N=C(CC=4C=CC=CC=4)C(=O)NC3=CC=2N=C1C(C=C1)=CC=C1C1=CC=NC=C1 BSSBAJKNZOHHCA-UHFFFAOYSA-N 0.000 description 15
• 208000031404 Chromosome Aberrations Diseases 0.000 description 15
• 244000061176 Nicotiana tabacum Species 0.000 description 15
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 15
• WDENQIQQYWYTPO-IBGZPJMESA-N acalabrutinib Chemical compound CC#CC(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C(=O)NC=2N=CC=CC=2)=C2N1C=CN=C2N WDENQIQQYWYTPO-IBGZPJMESA-N 0.000 description 15
• IJMHHZDBRUGXNO-UHFFFAOYSA-N n-[3-(8-anilinoimidazo[1,2-a]pyrazin-6-yl)phenyl]-4-tert-butylbenzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)NC1=CC=CC(C=2N=C(NC=3C=CC=CC=3)C3=NC=CN3C=2)=C1 IJMHHZDBRUGXNO-UHFFFAOYSA-N 0.000 description 15
• UVSVTDVJQAJIFG-VURMDHGXSA-N LFM-A13 Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC(Br)=CC=C1Br UVSVTDVJQAJIFG-VURMDHGXSA-N 0.000 description 14
• 108091000080 Phosphotransferase Proteins 0.000 description 14
• 238000001514 detection method Methods 0.000 description 14
• 230000000694 effects Effects 0.000 description 14
• 108020004999 messenger RNA Proteins 0.000 description 14
• 229960001156 mitoxantrone Drugs 0.000 description 14
• 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 description 14
• 102000020233 phosphotransferase Human genes 0.000 description 14
• 229940043355 kinase inhibitor Drugs 0.000 description 13
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 13
• CVCLJVVBHYOXDC-IAZSKANUSA-N (2z)-2-[(5z)-5-[(3,5-dimethyl-1h-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole Chemical compound COC1=C\C(=C/2N=C3C=CC=CC3=C\2)N\C1=C/C=1NC(C)=CC=1C CVCLJVVBHYOXDC-IAZSKANUSA-N 0.000 description 12
• SMOPKEHQPPXRSH-UHFFFAOYSA-N 2-methyl-n-[2-[3-[[2-(prop-2-enoylamino)acetyl]amino]anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide Chemical compound C1=C(C(=O)NC=2C=NC(NC=3C=C(NC(=O)CNC(=O)C=C)C=CC=3)=NC=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 SMOPKEHQPPXRSH-UHFFFAOYSA-N 0.000 description 12
• AQVFETGXIRKVAQ-UHFFFAOYSA-N 4-[3-(4-chlorophenyl)-2,1-benzisoxazol-5-yl]pyrimidin-2-amine Chemical compound NC1=NC=CC(C2=CC3=C(C=4C=CC(Cl)=CC=4)ON=C3C=C2)=N1 AQVFETGXIRKVAQ-UHFFFAOYSA-N 0.000 description 12
• 108091008875 B cell receptors Proteins 0.000 description 12
• 108010058546 Cyclin D1 Proteins 0.000 description 12
• 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 12
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical group NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
• 150000001875 compounds Chemical class 0.000 description 12
• 230000005945 translocation Effects 0.000 description 12
• 102000004190 Enzymes Human genes 0.000 description 11
• 108090000790 Enzymes Proteins 0.000 description 11
• 108060003951 Immunoglobulin Proteins 0.000 description 11
• 229940079156 Proteasome inhibitor Drugs 0.000 description 11
• 125000003275 alpha amino acid group Chemical group 0.000 description 11
• 229940088598 enzyme Drugs 0.000 description 11
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 11
• 102000018358 immunoglobulin Human genes 0.000 description 11
• DQPJVNQWPBLBAB-UHFFFAOYSA-N n-[5-[[3-(4-acetylpiperazine-1-carbonyl)-4,5-dimethylphenyl]methylsulfanyl]-1,3-thiazol-2-yl]-4-[(3,3-dimethylbutan-2-ylamino)methyl]benzamide Chemical compound C1=CC(CNC(C)C(C)(C)C)=CC=C1C(=O)NC(S1)=NC=C1SCC1=CC(C)=C(C)C(C(=O)N2CCN(CC2)C(C)=O)=C1 DQPJVNQWPBLBAB-UHFFFAOYSA-N 0.000 description 11
• 229950006584 obatoclax Drugs 0.000 description 11
• 239000003207 proteasome inhibitor Substances 0.000 description 11
• 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 10
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 10
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 10
• 210000001744 T-lymphocyte Anatomy 0.000 description 10
• 238000004458 analytical method Methods 0.000 description 10
• 230000003389 potentiating effect Effects 0.000 description 10
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 9
• 102100029234 Histone-lysine N-methyltransferase NSD2 Human genes 0.000 description 9
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 9
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 9
• 235000018417 cysteine Nutrition 0.000 description 9
• 238000011161 development Methods 0.000 description 9
• 230000018109 developmental process Effects 0.000 description 9
• 238000003780 insertion Methods 0.000 description 9
• 230000037431 insertion Effects 0.000 description 9
• 230000002018 overexpression Effects 0.000 description 9
• 102200162764 rs1057519825 Human genes 0.000 description 9
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
• HOZUXBLMYUPGPZ-UHFFFAOYSA-N 4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(O)C=C1 HOZUXBLMYUPGPZ-UHFFFAOYSA-N 0.000 description 8
• 101000634048 Homo sapiens Histone-lysine N-methyltransferase NSD2 Proteins 0.000 description 8
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 8
• 102220489126 Serine/threonine-protein kinase pim-1_P81S_mutation Human genes 0.000 description 8
• 102000042834 TEC family Human genes 0.000 description 8
• 108091082333 TEC family Proteins 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 230000002424 anti-apoptotic effect Effects 0.000 description 8
• 210000001185 bone marrow Anatomy 0.000 description 8
• 239000012634 fragment Substances 0.000 description 8
• 238000009396 hybridization Methods 0.000 description 8
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical group OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 7
• 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 7
• 102100027205 B-cell antigen receptor complex-associated protein alpha chain Human genes 0.000 description 7
• 102100021975 CREB-binding protein Human genes 0.000 description 7
• 101100016516 Caenorhabditis elegans hbl-1 gene Proteins 0.000 description 7
• 101000914489 Homo sapiens B-cell antigen receptor complex-associated protein alpha chain Proteins 0.000 description 7
• 101000896987 Homo sapiens CREB-binding protein Proteins 0.000 description 7
• 108010038036 Receptor Activator of Nuclear Factor-kappa B Proteins 0.000 description 7
• 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 7
• 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 7
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Chemical group OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 7
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 7
• 102100028787 Tumor necrosis factor receptor superfamily member 11A Human genes 0.000 description 7
• 239000012472 biological sample Substances 0.000 description 7
• 230000008859 change Effects 0.000 description 7
• 230000001419 dependent effect Effects 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 239000012530 fluid Substances 0.000 description 7
• 230000006870 function Effects 0.000 description 7
• IFSDAJWBUCMOAH-HNNXBMFYSA-N idelalisib Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)CC)=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1 IFSDAJWBUCMOAH-HNNXBMFYSA-N 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 210000004698 lymphocyte Anatomy 0.000 description 7
• 239000013610 patient sample Substances 0.000 description 7
• 230000004044 response Effects 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• 108091012583 BCL2 Proteins 0.000 description 6
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 238000002965 ELISA Methods 0.000 description 6
• 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 6
• 239000004471 Glycine Chemical group 0.000 description 6
• 101000738559 Homo sapiens G1/S-specific cyclin-D3 Proteins 0.000 description 6
• 101001005550 Homo sapiens Mitogen-activated protein kinase kinase kinase 14 Proteins 0.000 description 6
• 101000961071 Homo sapiens NF-kappa-B inhibitor alpha Proteins 0.000 description 6
• 101001051767 Homo sapiens Protein kinase C beta type Proteins 0.000 description 6
• 101000674728 Homo sapiens TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 Proteins 0.000 description 6
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 6
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 6
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical group CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical group CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 6
• 101150053046 MYD88 gene Proteins 0.000 description 6
• 102100025211 Mitogen-activated protein kinase kinase kinase 14 Human genes 0.000 description 6
• 102100024134 Myeloid differentiation primary response protein MyD88 Human genes 0.000 description 6
• 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 6
• 102000001253 Protein Kinase Human genes 0.000 description 6
• 102100024923 Protein kinase C beta type Human genes 0.000 description 6
• 102100021227 TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 Human genes 0.000 description 6
• 102000004399 TNF receptor-associated factor 3 Human genes 0.000 description 6
• 108090000922 TNF receptor-associated factor 3 Proteins 0.000 description 6
• 238000007792 addition Methods 0.000 description 6
• 125000000217 alkyl group Chemical group 0.000 description 6
• 230000006907 apoptotic process Effects 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 108010021331 carfilzomib Proteins 0.000 description 6
• BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical group 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 6
• 229960002438 carfilzomib Drugs 0.000 description 6
• 230000010261 cell growth Effects 0.000 description 6
• 238000003745 diagnosis Methods 0.000 description 6
• 210000001280 germinal center Anatomy 0.000 description 6
• 238000003199 nucleic acid amplification method Methods 0.000 description 6
• 230000011664 signaling Effects 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• 229960001350 tofacitinib Drugs 0.000 description 6
• UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 6
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 5
• 108020004414 DNA Proteins 0.000 description 5
• 241000282414 Homo sapiens Species 0.000 description 5
• 101000606067 Homo sapiens Tyrosine-protein kinase TXK Proteins 0.000 description 5
• 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 5
• 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 5
• 102000052575 Proto-Oncogene Human genes 0.000 description 5
• 108700020978 Proto-Oncogene Proteins 0.000 description 5
• 108010017121 Proto-Oncogene Proteins c-pim-1 Proteins 0.000 description 5
• 102000004433 Proto-Oncogene Proteins c-pim-1 Human genes 0.000 description 5
• 239000004012 Tofacitinib Substances 0.000 description 5
• 102100039079 Tyrosine-protein kinase TXK Human genes 0.000 description 5
• 230000003321 amplification Effects 0.000 description 5
• 125000003118 aryl group Chemical group 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 230000030833 cell death Effects 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
• 238000002372 labelling Methods 0.000 description 5
• 210000001165 lymph node Anatomy 0.000 description 5
• 230000035755 proliferation Effects 0.000 description 5
• 230000005855 radiation Effects 0.000 description 5
• 239000012453 solvate Substances 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• ASUGUQWIHMTFJL-QGZVFWFLSA-N (2r)-2-methyl-2-[[2-(1h-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]-n-(2,2,2-trifluoroethyl)butanamide Chemical compound FC(F)(F)CNC(=O)[C@@](C)(CC)NC1=CC=NC(C=2C3=CC=CN=C3NC=2)=N1 ASUGUQWIHMTFJL-QGZVFWFLSA-N 0.000 description 4
• JSASWRWALCMOQP-UHFFFAOYSA-N 1-(2-naphthalenyl)-3-[(phenylmethyl)-propan-2-ylamino]-1-propanone Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)CCN(C(C)C)CC1=CC=CC=C1 JSASWRWALCMOQP-UHFFFAOYSA-N 0.000 description 4
• KHJNISGKGIHTMY-UHFFFAOYSA-N 1-hydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]naphthalene-2-carboxamide Chemical compound C1=CC=CC2=C(O)C(C(=O)NCCC3=CNC4=CC=C(C=C43)O)=CC=C21 KHJNISGKGIHTMY-UHFFFAOYSA-N 0.000 description 4
• CBIAKDAYHRWZCU-UHFFFAOYSA-N 2-bromo-4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(O)C(Br)=C1 CBIAKDAYHRWZCU-UHFFFAOYSA-N 0.000 description 4
• CLGRAWDGLMENOD-UHFFFAOYSA-N 3-[5-[4-(2-hydroxy-2-methylpropanoyl)piperazin-1-yl]-2-(trifluoromethyl)phenyl]-4-(1h-indol-3-yl)pyrrole-2,5-dione Chemical compound C1CN(C(=O)C(C)(O)C)CCN1C1=CC=C(C(F)(F)F)C(C=2C(NC(=O)C=2C=2C3=CC=CC=C3NC=2)=O)=C1 CLGRAWDGLMENOD-UHFFFAOYSA-N 0.000 description 4
• XKJMBINCVNINCA-UHFFFAOYSA-N Alfalone Chemical compound CON(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XKJMBINCVNINCA-UHFFFAOYSA-N 0.000 description 4
• 108010004586 Ataxia Telangiectasia Mutated Proteins Proteins 0.000 description 4
• 102000002804 Ataxia Telangiectasia Mutated Proteins Human genes 0.000 description 4
• 102100027907 Cytoplasmic tyrosine-protein kinase BMX Human genes 0.000 description 4
• 101000935548 Homo sapiens Cytoplasmic tyrosine-protein kinase BMX Proteins 0.000 description 4
• 108010018650 MEF2 Transcription Factors Proteins 0.000 description 4
• 108020004711 Nucleic Acid Probes Proteins 0.000 description 4
• RONMOMUOZGIDET-HIFRSBDPSA-N PF-956980 Chemical compound C([C@H]([C@H](C1)N(C)C=2C=3C=CNC=3N=CN=2)C)CN1C(=O)N1CCCC1 RONMOMUOZGIDET-HIFRSBDPSA-N 0.000 description 4
• 229940124639 Selective inhibitor Drugs 0.000 description 4
• 206010042971 T-cell lymphoma Diseases 0.000 description 4
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 4
• JVDOKQYTTYUYDV-UHFFFAOYSA-N TG101209 Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C)C(NC=2C=C(C=CC=2)S(=O)(=O)NC(C)(C)C)=N1 JVDOKQYTTYUYDV-UHFFFAOYSA-N 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• 206010063092 Trisomy 12 Diseases 0.000 description 4
• 230000002159 abnormal effect Effects 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 230000015556 catabolic process Effects 0.000 description 4
• 238000004891 communication Methods 0.000 description 4
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
• 238000006731 degradation reaction Methods 0.000 description 4
• 238000012217 deletion Methods 0.000 description 4
• 230000037430 deletion Effects 0.000 description 4
• 239000012636 effector Substances 0.000 description 4
• 230000037433 frameshift Effects 0.000 description 4
• 238000003018 immunoassay Methods 0.000 description 4
• 229940072221 immunoglobulins Drugs 0.000 description 4
• 238000001114 immunoprecipitation Methods 0.000 description 4
• 239000003550 marker Substances 0.000 description 4
• ZUDPNBZMAJGYTE-HYMQDMCPSA-N methanesulfonic acid;(3z)-5-pyridin-3-yl-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound CS(O)(=O)=O.O=C1NC2=CC=C(C=3C=NC=CC=3)C=C2\C1=C\C1=CC=CN1 ZUDPNBZMAJGYTE-HYMQDMCPSA-N 0.000 description 4
• 238000002493 microarray Methods 0.000 description 4
• 239000002853 nucleic acid probe Substances 0.000 description 4
• 108060006633 protein kinase Proteins 0.000 description 4
• 108010083755 proto-oncogene proteins pim Proteins 0.000 description 4
• 238000001959 radiotherapy Methods 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 238000003757 reverse transcription PCR Methods 0.000 description 4
• 230000019491 signal transduction Effects 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• 230000002103 transcriptional effect Effects 0.000 description 4
• 238000001262 western blot Methods 0.000 description 4
• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical class C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 3
• FOTCGZPFSUWZBN-UHFFFAOYSA-N 1-(2-naphthalenyl)-2-propen-1-one Chemical compound C1=CC=CC2=CC(C(=O)C=C)=CC=C21 FOTCGZPFSUWZBN-UHFFFAOYSA-N 0.000 description 3
• 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 102100036597 Basement membrane-specific heparan sulfate proteoglycan core protein Human genes 0.000 description 3
• 102000051485 Bcl-2 family Human genes 0.000 description 3
• 108700038897 Bcl-2 family Proteins 0.000 description 3
• 102000011727 Caspases Human genes 0.000 description 3
• 108010076667 Caspases Proteins 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 3
• 101000599886 Homo sapiens Isocitrate dehydrogenase [NADP], mitochondrial Proteins 0.000 description 3
• 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 3
• 102100037845 Isocitrate dehydrogenase [NADP], mitochondrial Human genes 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 101100297651 Mus musculus Pim2 gene Proteins 0.000 description 3
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
• 238000000636 Northern blotting Methods 0.000 description 3
• 102000001756 Notch2 Receptor Human genes 0.000 description 3
• 108010029751 Notch2 Receptor Proteins 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 101150056413 Pim1 gene Proteins 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 102100024333 Toll-like receptor 2 Human genes 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 3
• 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 239000003183 carcinogenic agent Substances 0.000 description 3
• 230000006369 cell cycle progression Effects 0.000 description 3
• 238000006243 chemical reaction Methods 0.000 description 3
• 238000002512 chemotherapy Methods 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000011284 combination treatment Methods 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 230000009422 growth inhibiting effect Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 229960003648 ixazomib Drugs 0.000 description 3
• 210000004324 lymphatic system Anatomy 0.000 description 3
• 210000000207 lymphocyte subset Anatomy 0.000 description 3
• 229950002736 marizomib Drugs 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• 229960004961 mechlorethamine Drugs 0.000 description 3
• 239000002773 nucleotide Substances 0.000 description 3
• 125000003729 nucleotide group Chemical group 0.000 description 3
• 230000000737 periodic effect Effects 0.000 description 3
• 230000001566 pro-viral effect Effects 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 238000004393 prognosis Methods 0.000 description 3
• 238000003127 radioimmunoassay Methods 0.000 description 3
• 230000000306 recurrent effect Effects 0.000 description 3
• 102220025225 rs199476363 Human genes 0.000 description 3
• NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 description 3
• 238000012916 structural analysis Methods 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 230000014616 translation Effects 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• 229940099039 velcade Drugs 0.000 description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 2
• YTXSYWAKVMZICI-PVCZSOGJSA-N 4-(carboxymethyl)-2-[(1r)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-6-oxo-1,3,2-dioxaborinane-4-carboxylic acid Chemical compound N([C@@H](CC(C)C)B1OC(CC(O)=O)(CC(=O)O1)C(O)=O)C(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl YTXSYWAKVMZICI-PVCZSOGJSA-N 0.000 description 2
• 125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
• RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 description 2
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
• 125000003341 7 membered heterocyclic group Chemical group 0.000 description 2
• 125000005330 8 membered heterocyclic group Chemical group 0.000 description 2
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
• 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 2
• 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 2
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
• 108700003785 Baculoviral IAP Repeat-Containing 3 Proteins 0.000 description 2
• 102000051819 Baculoviral IAP Repeat-Containing 3 Human genes 0.000 description 2
• 108010006654 Bleomycin Proteins 0.000 description 2
• 201000004085 CLL/SLL Diseases 0.000 description 2
• 102000014914 Carrier Proteins Human genes 0.000 description 2
• 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
• 206010053567 Coagulopathies Diseases 0.000 description 2
• 230000004544 DNA amplification Effects 0.000 description 2
• 108010092160 Dactinomycin Proteins 0.000 description 2
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 102100030013 Endoribonuclease Human genes 0.000 description 2
• 101710199605 Endoribonuclease Proteins 0.000 description 2
• 108010087819 Fc receptors Proteins 0.000 description 2
• 102000009109 Fc receptors Human genes 0.000 description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 102000003886 Glycoproteins Human genes 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 208000017604 Hodgkin disease Diseases 0.000 description 2
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
• 101000957807 Homo sapiens Mucosa-associated lymphoid tissue lymphoma translocation protein 1 Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 102000055120 MEF2 Transcription Factors Human genes 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 241000713869 Moloney murine leukemia virus Species 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 102100021149 Myocyte-specific enhancer factor 2B Human genes 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• XFAZZQREFHAALG-UHFFFAOYSA-N N-{1-amino-6-[(5-nitro-2-furoyl)amino]-1-oxohexan-2-yl}-23-(indol-3-yl)-20-oxo-4,7,10,13,16-pentaoxa-19-azatricosan-1-amide Chemical compound C=1NC2=CC=CC=C2C=1CCCC(=O)NCCOCCOCCOCCOCCOCCC(=O)NC(C(=O)N)CCCCNC(=O)C1=CC=C([N+]([O-])=O)O1 XFAZZQREFHAALG-UHFFFAOYSA-N 0.000 description 2
• 108010057466 NF-kappa B Proteins 0.000 description 2
• 102000003945 NF-kappa B Human genes 0.000 description 2
• 102000001759 Notch1 Receptor Human genes 0.000 description 2
• 108010029755 Notch1 Receptor Proteins 0.000 description 2
• 108091028043 Nucleic acid sequence Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 102100035548 Protein Bop Human genes 0.000 description 2
• 108050008794 Protein Bop Proteins 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
• 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 102220564322 Tyrosine-protein kinase BTK_I370M_mutation Human genes 0.000 description 2
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 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 description 2
• 230000004913 activation Effects 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 230000000719 anti-leukaemic effect Effects 0.000 description 2
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 2
• 238000003491 array Methods 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 108091008324 binding proteins Proteins 0.000 description 2
• 239000003124 biologic agent Substances 0.000 description 2
• 229960001561 bleomycin Drugs 0.000 description 2
• 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 description 2
• 230000017531 blood circulation Effects 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 230000011712 cell development Effects 0.000 description 2
• 230000024245 cell differentiation Effects 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 201000003778 chromosome 13q14 deletion syndrome Diseases 0.000 description 2
• 208000023738 chronic lymphocytic leukemia/small lymphocytic lymphoma Diseases 0.000 description 2
• 230000035602 clotting Effects 0.000 description 2
• 230000000295 complement effect Effects 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 2
• 210000000805 cytoplasm Anatomy 0.000 description 2
• 229960003901 dacarbazine Drugs 0.000 description 2
• 231100000517 death Toxicity 0.000 description 2
• 230000003412 degenerative effect Effects 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000010586 diagram Methods 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 239000000835 fiber Substances 0.000 description 2
• 229930003935 flavonoid Natural products 0.000 description 2
• 235000017173 flavonoids Nutrition 0.000 description 2
• 238000000684 flow cytometry Methods 0.000 description 2
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
• 239000007850 fluorescent dye Substances 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 230000004077 genetic alteration Effects 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 125000001072 heteroaryl group Chemical group 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• 150000004942 imidazo[1,2-b]pyridazines Chemical class 0.000 description 2
• 238000003364 immunohistochemistry Methods 0.000 description 2
• 238000012309 immunohistochemistry technique Methods 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000002779 inactivation Effects 0.000 description 2
• 230000002427 irreversible effect Effects 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 238000000302 molecular modelling Methods 0.000 description 2
• 210000000822 natural killer cell Anatomy 0.000 description 2
• 229960001756 oxaliplatin Drugs 0.000 description 2
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
• 230000002085 persistent effect Effects 0.000 description 2
• 239000008194 pharmaceutical composition Substances 0.000 description 2
• 150000002990 phenothiazines Chemical class 0.000 description 2
• 210000004180 plasmocyte Anatomy 0.000 description 2
• 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 2
• 230000000861 pro-apoptotic effect Effects 0.000 description 2
• 229960000624 procarbazine Drugs 0.000 description 2
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 2
• 239000003909 protein kinase inhibitor Substances 0.000 description 2
• 230000007115 recruitment Effects 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 229910052707 ruthenium Inorganic materials 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• NGWSFRIPKNWYAO-UHFFFAOYSA-N salinosporamide A Natural products N1C(=O)C(CCCl)C2(C)OC(=O)C21C(O)C1CCCC=C1 NGWSFRIPKNWYAO-UHFFFAOYSA-N 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000002459 sustained effect Effects 0.000 description 2
• 239000011885 synergistic combination Substances 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• 229960000237 vorinostat Drugs 0.000 description 2
• WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 2
• 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 1
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
• 229930014124 (-)-epigallocatechin gallate Natural products 0.000 description 1
• FWPWHHUJACGNMZ-NBBQQVJHSA-N (1s,2r,5r)-5-[(1s)-1-hydroxy-2-methylpropyl]-2-methyl-7-oxa-4-azabicyclo[3.2.0]heptane-3,6-dione Chemical compound N1C(=O)[C@H](C)[C@@H]2OC(=O)[C@@]21[C@@H](O)C(C)C FWPWHHUJACGNMZ-NBBQQVJHSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• MFXAGCQVWGPEJH-LRSLUSHPSA-N (2s)-2-[[(2s)-4-amino-2-[[(3r)-3-hydroxydodecanoyl]amino]-4-oxobutanoyl]amino]-n-[(2s)-4-methyl-1-oxopentan-2-yl]pentanediamide Chemical compound CCCCCCCCC[C@@H](O)CC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C=O MFXAGCQVWGPEJH-LRSLUSHPSA-N 0.000 description 1
• XERVAQYNJKWPRP-CACGZCQESA-N (2s)-n-[(2r)-1-[(2,6-difluorophenyl)methylamino]-4-methyl-1-oxopentan-2-yl]-2-[[2-(6-methoxy-3-oxo-1,2-dihydroinden-1-yl)acetyl]amino]-4-methylpentanamide Chemical compound O=C([C@@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)CC1CC(=O)C2=CC=C(C=C21)OC)NCC1=C(F)C=CC=C1F XERVAQYNJKWPRP-CACGZCQESA-N 0.000 description 1
• MXGWDBFUMHUPTG-SKZNYKRCSA-N (4S,7S,13R,22R)-4-(1H-indol-3-ylmethyl)-7-[(4-methoxy-1H-indol-3-yl)methyl]-13,18,22-trimethyl-16-methylidene-24-thia-3,6,9,12,15,18,21,26-octazabicyclo[21.2.1]hexacosa-1(25),23(26)-diene-2,5,8,11,14,17,20-heptone Chemical compound N([C@H](C(NCC(=O)N[C@H](C)C(=O)NC(=C)C(=O)N(C)CC(=O)N[C@H](C)C=1SC=C(N=1)C(=O)N1)=O)CC2=CNC=3C=CC=C(C2=3)OC)C(=O)[C@@H]1CC1=CNC2=CC=CC=C12 MXGWDBFUMHUPTG-SKZNYKRCSA-N 0.000 description 1
• HWXBTNAVRSUOJR-GSVOUGTGSA-N (R)-2-hydroxyglutaric acid Chemical compound OC(=O)[C@H](O)CCC(O)=O HWXBTNAVRSUOJR-GSVOUGTGSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• QFMSRGZWWJLTQE-UHFFFAOYSA-N 1h-[1]benzothiolo[3,2-d]pyrimidin-4-one Chemical class C12=CC=CC=C2SC2=C1NC=NC2=O QFMSRGZWWJLTQE-UHFFFAOYSA-N 0.000 description 1
• RZCJYMOBWVJQGV-UHFFFAOYSA-N 2-naphthyloxyacetic acid Chemical compound C1=CC=CC2=CC(OCC(=O)O)=CC=C21 RZCJYMOBWVJQGV-UHFFFAOYSA-N 0.000 description 1
• KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
• LFASPBCAVCUZES-UHFFFAOYSA-N 2h-pyrrolo[1,2-a]pyrazin-1-one Chemical class O=C1NC=CN2C=CC=C12 LFASPBCAVCUZES-UHFFFAOYSA-N 0.000 description 1
• 101150090724 3 gene Proteins 0.000 description 1
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
• UZFPOOOQHWICKY-UHFFFAOYSA-N 3-[13-[1-[1-[8,12-bis(2-carboxyethyl)-17-(1-hydroxyethyl)-3,7,13,18-tetramethyl-21,24-dihydroporphyrin-2-yl]ethoxy]ethyl]-18-(2-carboxyethyl)-8-(1-hydroxyethyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoic acid Chemical compound N1C(C=C2C(=C(CCC(O)=O)C(C=C3C(=C(C)C(C=C4N5)=N3)CCC(O)=O)=N2)C)=C(C)C(C(C)O)=C1C=C5C(C)=C4C(C)OC(C)C1=C(N2)C=C(N3)C(C)=C(C(O)C)C3=CC(C(C)=C3CCC(O)=O)=NC3=CC(C(CCC(O)=O)=C3C)=NC3=CC2=C1C UZFPOOOQHWICKY-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ZOLNSECVOZFNLU-UHFFFAOYSA-N 3h-1,2-benzoxathiole Chemical class C1=CC=C2CSOC2=C1 ZOLNSECVOZFNLU-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• RILCLFZXOSENQY-UHFFFAOYSA-N 4a,8,12b-trihydroxy-9-(3-hydroxy-2,9-dimethyl-2,3,4,4a,5a,6,7,9,9a,10a-decahydrodipyrano[3,2-[1,4]dioxin-7-yl)-3-methyl-3-[6-methyl-5-[(6-methyl-5-oxo-2h-pyran-2-yl)oxy]oxan-2-yl]oxy-2,4-dihydrobenzo[a]anthracene-1,7,12-trione Chemical compound C1C2OC3CC(O)C(C)OC3OC2C(C)OC1C(C(=C1C2=O)O)=CC=C1C(=O)C(C1(C(=O)C3)O)=C2C=CC1(O)CC3(C)OC(OC1C)CCC1OC1OC(C)C(=O)C=C1 RILCLFZXOSENQY-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
• 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 description 1
• LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
• KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
• 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
• 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
• 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 description 1
• ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
• 241000186361 Actinobacteria <class> Species 0.000 description 1
• 206010000830 Acute leukaemia Diseases 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 230000007730 Akt signaling Effects 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 241000156724 Antirhea Species 0.000 description 1
• 101100125460 Arabidopsis thaliana IDH3 gene Proteins 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• 101150065175 Atm gene Proteins 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 108700024832 B-Cell CLL-Lymphoma 10 Proteins 0.000 description 1
• 102100027203 B-cell antigen receptor complex-associated protein beta chain Human genes 0.000 description 1
• 102100037598 B-cell lymphoma/leukemia 10 Human genes 0.000 description 1
• 101150074953 BCL10 gene Proteins 0.000 description 1
• 108091007065 BIRCs Proteins 0.000 description 1
• 101100160805 Bacillus subtilis (strain 168) yxaF gene Proteins 0.000 description 1
• 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 102100026189 Beta-galactosidase Human genes 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 1
• FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• 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 description 1
• SHHKQEUPHAENFK-UHFFFAOYSA-N Carboquone Chemical compound O=C1C(C)=C(N2CC2)C(=O)C(C(COC(N)=O)OC)=C1N1CC1 SHHKQEUPHAENFK-UHFFFAOYSA-N 0.000 description 1
• AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
• 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
• 102220544638 Cell cycle progression protein 1_Y418H_mutation Human genes 0.000 description 1
• GEWLYFZWVLXQME-UHFFFAOYSA-N Cercosporamide Natural products CC12C(=O)C(C(=O)C)=C(O)C=C1OC1=C2C(O)=CC(O)=C1C(N)=O GEWLYFZWVLXQME-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 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
• 102220519361 Coatomer subunit alpha_C17S_mutation Human genes 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 108091029523 CpG island Proteins 0.000 description 1
• 102000009508 Cyclin-Dependent Kinase Inhibitor p16 Human genes 0.000 description 1
• 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• 206010067477 Cytogenetic abnormality Diseases 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 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
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 238000000018 DNA microarray Methods 0.000 description 1
• 230000033616 DNA repair Effects 0.000 description 1
• 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
• 108700020911 DNA-Binding Proteins 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
• 108010086291 Deubiquitinating Enzyme CYLD Proteins 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
• 108010016626 Dipeptides Proteins 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• 102100028554 Dual specificity tyrosine-phosphorylation-regulated kinase 1A Human genes 0.000 description 1
• 108010040648 Dyrk kinase Proteins 0.000 description 1
• 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 description 1
• 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 description 1
• 102220500865 F-box only protein 38_S592P_mutation Human genes 0.000 description 1
• MFXAGCQVWGPEJH-UHFFFAOYSA-N Fellutamide B Natural products CCCCCCCCCC(O)CC(=O)NC(CC(N)=O)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C=O MFXAGCQVWGPEJH-UHFFFAOYSA-N 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
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 102220552010 Gamma-aminobutyric acid receptor subunit beta-1_I429N_mutation Human genes 0.000 description 1
• 208000034951 Genetic Translocation Diseases 0.000 description 1
• 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
• 101100356020 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) recA gene Proteins 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 108010036115 Histone Methyltransferases Proteins 0.000 description 1
• 102000011787 Histone Methyltransferases Human genes 0.000 description 1
• 108090000353 Histone deacetylase Proteins 0.000 description 1
• 102100038720 Histone deacetylase 9 Human genes 0.000 description 1
• 101710196680 Histone-lysine N-methyltransferase NSD2 Proteins 0.000 description 1
• 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
• 101000914491 Homo sapiens B-cell antigen receptor complex-associated protein beta chain Proteins 0.000 description 1
• 101000653374 Homo sapiens Methylcytosine dioxygenase TET2 Proteins 0.000 description 1
• 101001109719 Homo sapiens Nucleophosmin Proteins 0.000 description 1
• 101100521072 Homo sapiens PRDM1 gene Proteins 0.000 description 1
• 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
• 101000785063 Homo sapiens Serine-protein kinase ATM Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101001052849 Homo sapiens Tyrosine-protein kinase Fer Proteins 0.000 description 1
• 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• 101150090950 Hsc70-1 gene Proteins 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
• 101150009025 IRC3 gene Proteins 0.000 description 1
• 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 description 1
• 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 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 102100024319 Intestinal-type alkaline phosphatase Human genes 0.000 description 1
• PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
• KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 description 1
• 102000042838 JAK family Human genes 0.000 description 1
• 108091082332 JAK family Proteins 0.000 description 1
• 108050000950 Janus Proteins 0.000 description 1
• 102000008986 Janus Human genes 0.000 description 1
• 102220564773 Killer cell immunoglobulin-like receptor 2DS5_H68D_mutation Human genes 0.000 description 1
• 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 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 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
• 206010025280 Lymphocytosis Diseases 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 102000042106 MEF2 family Human genes 0.000 description 1
• 108091077694 MEF2 family Proteins 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 102100025169 Max-binding protein MNT Human genes 0.000 description 1
• 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 1
• 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 102100030803 Methylcytosine dioxygenase TET2 Human genes 0.000 description 1
• 108060004795 Methyltransferase Proteins 0.000 description 1
• 102000016397 Methyltransferase Human genes 0.000 description 1
• 108091033773 MiR-155 Proteins 0.000 description 1
• 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 description 1
• 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 description 1
• 229930192392 Mitomycin Natural products 0.000 description 1
• 101710172604 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 Proteins 0.000 description 1
• 101001026869 Mus musculus F-box/LRR-repeat protein 3 Proteins 0.000 description 1
• 101100042680 Mus musculus Slc7a1 gene Proteins 0.000 description 1
• 101710150912 Myc protein Proteins 0.000 description 1
• 102220609669 Myocyte-specific enhancer factor 2A_S97T_mutation Human genes 0.000 description 1
• 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 description 1
• LYPFDBRUNKHDGX-SOGSVHMOSA-N N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 Chemical compound N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 LYPFDBRUNKHDGX-SOGSVHMOSA-N 0.000 description 1
• 102220497999 Neuronal growth regulator 1_G594E_mutation Human genes 0.000 description 1
• 101100179449 Nicotiana tabacum A622 gene Proteins 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• 101150079595 Notch1 gene Proteins 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 102100022678 Nucleophosmin Human genes 0.000 description 1
• 108010027206 Nucleopolyhedrovirus inhibitor of apoptosis Proteins 0.000 description 1
• 108010064641 ONX 0912 Proteins 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 102220540445 Ovarian cancer-related protein 1_Y44S_mutation Human genes 0.000 description 1
• 239000012661 PARP inhibitor Substances 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• KMXHEXRPYSXLRN-JDVQERKKSA-N PS-519 Chemical compound N1C(=O)[C@H](CCC)[C@@H]2OC(=O)[C@@]21[C@@H](O)C(C)C KMXHEXRPYSXLRN-JDVQERKKSA-N 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 101710120145 Paracaspase Proteins 0.000 description 1
• 208000010995 Partial deletion of the long arm of chromosome 11 Diseases 0.000 description 1
• 208000010954 Partial deletion of the long arm of chromosome 7 Diseases 0.000 description 1
• 102000057297 Pepsin A Human genes 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 101710176384 Peptide 1 Proteins 0.000 description 1
• 208000005228 Pericardial Effusion Diseases 0.000 description 1
• 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
• 102220638759 Phosphomannomutase 2_Q37H_mutation Human genes 0.000 description 1
• 229940122016 Pim kinase inhibitor Drugs 0.000 description 1
• 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 description 1
• 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 1
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
• HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 1
• 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102100032420 Protein S100-A9 Human genes 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 108010066717 Q beta Replicase Proteins 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 238000002123 RNA extraction Methods 0.000 description 1
• AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 1
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
• 241000606701 Rickettsia Species 0.000 description 1
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
• 102220469108 S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1_G462V_mutation Human genes 0.000 description 1
• 101100365883 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SLG1 gene Proteins 0.000 description 1
• 101100150366 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sks2 gene Proteins 0.000 description 1
• 101100156779 Schizosaccharomyces pombe (strain 972 / ATCC 24843) wsc1 gene Proteins 0.000 description 1
• HJKXQQVDTIEFDD-FAVUQDIBSA-N Scytonemide A Chemical compound N/1=C/[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](CCC(N)=O)NC(=O)CNC(=O)[C@@H]\1CC1=CC=C(O)C=C1 HJKXQQVDTIEFDD-FAVUQDIBSA-N 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 208000019802 Sexually transmitted disease Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
• 108091008874 T cell receptors Proteins 0.000 description 1
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
• ZIAXNZCTODBCKW-UHFFFAOYSA-N TMC-95 C Natural products C12=CC=CC3=C2NC(=O)C3(O)C(O)C(C(=O)NC=CC)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(=O)C(C)CC)CC2=CC=C(O)C1=C2 ZIAXNZCTODBCKW-UHFFFAOYSA-N 0.000 description 1
• 102000004398 TNF receptor-associated factor 1 Human genes 0.000 description 1
• 108090000920 TNF receptor-associated factor 1 Proteins 0.000 description 1
• 108090000925 TNF receptor-associated factor 2 Proteins 0.000 description 1
• 102000003714 TNF receptor-associated factor 6 Human genes 0.000 description 1
• 108090000009 TNF receptor-associated factor 6 Proteins 0.000 description 1
• 102100034779 TRAF family member-associated NF-kappa-B activator Human genes 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• RMMPZDDLWLALLJ-UHFFFAOYSA-N Thermophillin Chemical compound COC1=CC(=O)C(OC)=CC1=O RMMPZDDLWLALLJ-UHFFFAOYSA-N 0.000 description 1
• FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
• IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
• UMILHIMHKXVDGH-UHFFFAOYSA-N Triethylene glycol diglycidyl ether Chemical compound C1OC1COCCOCCOCCOCC1CO1 UMILHIMHKXVDGH-UHFFFAOYSA-N 0.000 description 1
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
• 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
• 102220564469 Tyrosine-protein kinase BTK_A508D_mutation Human genes 0.000 description 1
• 102220564531 Tyrosine-protein kinase BTK_A523E_mutation Human genes 0.000 description 1
• 102220564389 Tyrosine-protein kinase BTK_A622P_mutation Human genes 0.000 description 1
• 102220564345 Tyrosine-protein kinase BTK_C502F_mutation Human genes 0.000 description 1
• 102220564360 Tyrosine-protein kinase BTK_C502W_mutation Human genes 0.000 description 1
• 102220577206 Tyrosine-protein kinase BTK_C633Y_mutation Human genes 0.000 description 1
• 102220564477 Tyrosine-protein kinase BTK_D521H_mutation Human genes 0.000 description 1
• 102220564376 Tyrosine-protein kinase BTK_E589D_mutation Human genes 0.000 description 1
• 102220563343 Tyrosine-protein kinase BTK_F25S_mutation Human genes 0.000 description 1
• 102220564537 Tyrosine-protein kinase BTK_F559S_mutation Human genes 0.000 description 1
• 102220564363 Tyrosine-protein kinase BTK_F583S_mutation Human genes 0.000 description 1
• 102220577207 Tyrosine-protein kinase BTK_F644L_mutation Human genes 0.000 description 1
• 102220564257 Tyrosine-protein kinase BTK_H364P_mutation Human genes 0.000 description 1
• 102220563159 Tyrosine-protein kinase BTK_I61N_mutation Human genes 0.000 description 1
• 102220563339 Tyrosine-protein kinase BTK_K12R_mutation Human genes 0.000 description 1
• 102220563342 Tyrosine-protein kinase BTK_K19E_mutation Human genes 0.000 description 1
• 102220563350 Tyrosine-protein kinase BTK_K27R_mutation Human genes 0.000 description 1
• 102220563338 Tyrosine-protein kinase BTK_L11P_mutation Human genes 0.000 description 1
• 102220564470 Tyrosine-protein kinase BTK_M509I_mutation Human genes 0.000 description 1
• 102220577204 Tyrosine-protein kinase BTK_M630I_mutation Human genes 0.000 description 1
• 102220577202 Tyrosine-protein kinase BTK_M630T_mutation Human genes 0.000 description 1
• 102220564387 Tyrosine-protein kinase BTK_P619A_mutation Human genes 0.000 description 1
• 102220563341 Tyrosine-protein kinase BTK_R28C_mutation Human genes 0.000 description 1
• 102220563347 Tyrosine-protein kinase BTK_R28P_mutation Human genes 0.000 description 1
• 102220564277 Tyrosine-protein kinase BTK_R307T_mutation Human genes 0.000 description 1
• 102220564539 Tyrosine-protein kinase BTK_R525P_mutation Human genes 0.000 description 1
• 102220564516 Tyrosine-protein kinase BTK_R544G_mutation Human genes 0.000 description 1
• 102220577205 Tyrosine-protein kinase BTK_R641C_mutation Human genes 0.000 description 1
• 102220563160 Tyrosine-protein kinase BTK_R82K_mutation Human genes 0.000 description 1
• 102220563337 Tyrosine-protein kinase BTK_S14F_mutation Human genes 0.000 description 1
• 102220564312 Tyrosine-protein kinase BTK_S366F_mutation Human genes 0.000 description 1
• 102220563168 Tyrosine-protein kinase BTK_T117P_mutation Human genes 0.000 description 1
• 102220563165 Tyrosine-protein kinase BTK_T184P_mutation Human genes 0.000 description 1
• 102220564252 Tyrosine-protein kinase BTK_V319A_mutation Human genes 0.000 description 1
• 102220564532 Tyrosine-protein kinase BTK_V535F_mutation Human genes 0.000 description 1
• 102220563164 Tyrosine-protein kinase BTK_V64D_mutation Human genes 0.000 description 1
• 102220563151 Tyrosine-protein kinase BTK_V64F_mutation Human genes 0.000 description 1
• 102220577218 Tyrosine-protein kinase BTK_W251L_mutation Human genes 0.000 description 1
• 102220563349 Tyrosine-protein kinase BTK_Y40N_mutation Human genes 0.000 description 1
• 102220564356 Tyrosine-protein kinase BTK_Y476D_mutation Human genes 0.000 description 1
• 102220577209 Tyrosine-protein kinase BTK_Y551F_mutation Human genes 0.000 description 1
• 102220577212 Tyrosine-protein kinase BTK_Y617E_mutation Human genes 0.000 description 1
• 102100024537 Tyrosine-protein kinase Fer Human genes 0.000 description 1
• 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 1
• 102000044159 Ubiquitin Human genes 0.000 description 1
• 108090000848 Ubiquitin Proteins 0.000 description 1
• 102100024250 Ubiquitin carboxyl-terminal hydrolase CYLD Human genes 0.000 description 1
• LZDNBBYBDGBADK-KBPBESRZSA-N Val-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-KBPBESRZSA-N 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 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 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 238000002679 ablation Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A 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=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 1
• 229960004176 aclarubicin Drugs 0.000 description 1
• 229930183665 actinomycin Natural products 0.000 description 1
• 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 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000011543 agarose gel Substances 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
• 150000008052 alkyl sulfonates Chemical class 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229960002749 aminolevulinic acid Drugs 0.000 description 1
• 210000004381 amniotic fluid Anatomy 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
• 229940045695 antineooplastic colchicine derivative Drugs 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 229940045696 antineoplastic drug podophyllotoxin derivative Drugs 0.000 description 1
• 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 108010003647 argyrin A Proteins 0.000 description 1
• MXGWDBFUMHUPTG-UHFFFAOYSA-N argyrin A Natural products C1=2C(OC)=CC=CC=2NC=C1CC(C(NCC(=O)NC(C)C(=O)NC(=C)C(=O)N(C)CC(=O)NC(C)C=1SC=C(N=1)C(=O)N1)=O)NC(=O)C1CC1=CNC2=CC=CC=C12 MXGWDBFUMHUPTG-UHFFFAOYSA-N 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 210000003567 ascitic fluid Anatomy 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 229960002756 azacitidine Drugs 0.000 description 1
• 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 description 1
• 239000002585 base Substances 0.000 description 1
• 229960002707 bendamustine Drugs 0.000 description 1
• YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• WIPHXOQUHDJLCU-WTJMUODPSA-N benzyl N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-2-[[6-(diaminomethylideneamino)-1-fluoro-2-oxohexan-3-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NC(CCCN=C(N)N)C(=O)CF WIPHXOQUHDJLCU-WTJMUODPSA-N 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 238000012925 biological evaluation Methods 0.000 description 1
• 238000001815 biotherapy Methods 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 238000004820 blood count Methods 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 238000010322 bone marrow transplantation Methods 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 229960002092 busulfan Drugs 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• XUPYJHCZDLZNFP-UHFFFAOYSA-N butyl ester butanoic acid Natural products CCCCOC(=O)CCC XUPYJHCZDLZNFP-UHFFFAOYSA-N 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 102220359327 c.1086C>G Human genes 0.000 description 1
• 102220352968 c.1573C>G Human genes 0.000 description 1
• 102200105112 c.1855C>T Human genes 0.000 description 1
• 102220346513 c.241C>G Human genes 0.000 description 1
• 102220344959 c.8180T>C Human genes 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229960005069 calcium Drugs 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 230000000711 cancerogenic effect Effects 0.000 description 1
• 229960004117 capecitabine Drugs 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 229960002115 carboquone Drugs 0.000 description 1
• 229960003261 carmofur Drugs 0.000 description 1
• 229960005243 carmustine Drugs 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000009134 cell regulation Effects 0.000 description 1
• 230000003833 cell viability Effects 0.000 description 1
• 238000003570 cell viability assay Methods 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 230000004637 cellular stress Effects 0.000 description 1
• GEWLYFZWVLXQME-MRXNPFEDSA-N cercosporamide Chemical compound O=C([C@]12C)C(C(=O)C)=C(O)C=C1OC1=C2C(O)=CC(O)=C1C(N)=O GEWLYFZWVLXQME-MRXNPFEDSA-N 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
• 238000012412 chemical coupling Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 229940044683 chemotherapy drug Drugs 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 201000001329 chromosome 9p deletion syndrome Diseases 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 229960002436 cladribine 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
• 229960000928 clofarabine Drugs 0.000 description 1
• 230000003021 clonogenic effect Effects 0.000 description 1
• 229960001338 colchicine Drugs 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 230000009137 competitive binding Effects 0.000 description 1
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 238000012866 crystallographic experiment Methods 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 238000005520 cutting process Methods 0.000 description 1
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 210000005220 cytoplasmic tail Anatomy 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 229960000640 dactinomycin Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• 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 description 1
• 230000034994 death Effects 0.000 description 1
• 229960003603 decitabine Drugs 0.000 description 1
• SJFBTAPEPRWNKH-CCKFTAQKSA-N delanzomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)C1=CC=CC(C=2C=CC=CC=2)=N1 SJFBTAPEPRWNKH-CCKFTAQKSA-N 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 238000002059 diagnostic imaging Methods 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 229960002563 disulfiram Drugs 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• BNFRJXLZYUTIII-UHFFFAOYSA-N efaproxiral Chemical compound CC1=CC(C)=CC(NC(=O)CC=2C=CC(OC(C)(C)C(O)=O)=CC=2)=C1 BNFRJXLZYUTIII-UHFFFAOYSA-N 0.000 description 1
• 229960000925 efaproxiral Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 230000004076 epigenetic alteration Effects 0.000 description 1
• 230000001973 epigenetic effect Effects 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• 108700002672 epoxomicin Proteins 0.000 description 1
• DOGIDQKFVLKMLQ-JTHVHQAWSA-N epoxomicin Chemical compound CC[C@H](C)[C@H](N(C)C(C)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1 DOGIDQKFVLKMLQ-JTHVHQAWSA-N 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 229960005237 etoglucid Drugs 0.000 description 1
• 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 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 108010063626 fellutamide B Proteins 0.000 description 1
• 229960002428 fentanyl Drugs 0.000 description 1
• IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 1
• 210000004700 fetal blood Anatomy 0.000 description 1
• 150000002215 flavonoids Chemical class 0.000 description 1
• 238000001215 fluorescent labelling Methods 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• 229960004783 fotemustine Drugs 0.000 description 1
• YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 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 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 231100000118 genetic alteration Toxicity 0.000 description 1
• 238000009650 gentamicin protection assay Methods 0.000 description 1
• 210000001102 germinal center b cell Anatomy 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 239000001806 glycerol esters of wood rosin Substances 0.000 description 1
• 235000010985 glycerol esters of wood rosin Nutrition 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 230000007773 growth pattern Effects 0.000 description 1
• 210000003780 hair follicle Anatomy 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 125000004404 heteroalkyl group Chemical group 0.000 description 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 229960000908 idarubicin Drugs 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000037451 immune surveillance Effects 0.000 description 1
• 238000003119 immunoblot Methods 0.000 description 1
• 230000000951 immunodiffusion Effects 0.000 description 1
• 238000000760 immunoelectrophoresis Methods 0.000 description 1
• 238000010166 immunofluorescence Methods 0.000 description 1
• 238000013394 immunophenotyping Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000007901 in situ hybridization Methods 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000034727 intrinsic apoptotic signaling pathway Effects 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• ODBLHEXUDAPZAU-UHFFFAOYSA-N isocitric acid Chemical compound OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 description 1
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
• 229940011051 isopropyl acetate Drugs 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 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
• 229960002014 ixabepilone Drugs 0.000 description 1
• MXAYKZJJDUDWDS-LBPRGKRZSA-N ixazomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MXAYKZJJDUDWDS-LBPRGKRZSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 238000007834 ligase chain reaction Methods 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229960002247 lomustine Drugs 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 238000010841 mRNA extraction Methods 0.000 description 1
• 230000005291 magnetic effect Effects 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• UUVIQYKKKBJYJT-ZYUZMQFOSA-N mannosulfan Chemical compound CS(=O)(=O)OC[C@@H](OS(C)(=O)=O)[C@@H](O)[C@H](O)[C@H](OS(C)(=O)=O)COS(C)(=O)=O UUVIQYKKKBJYJT-ZYUZMQFOSA-N 0.000 description 1
• 229960000733 mannosulfan Drugs 0.000 description 1
• 210000003826 marginal zone b cell Anatomy 0.000 description 1
• 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• 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 1
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• 229960005033 methyl aminolevulinate Drugs 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
• 229960005485 mitobronitol Drugs 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 238000003032 molecular docking Methods 0.000 description 1
• 230000000877 morphologic effect Effects 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• SWZXEVABPLUDIO-WSZYKNRRSA-N n-[(2s)-3-methoxy-1-[[(2s)-3-methoxy-1-[[(2s)-1-[(2r)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide Chemical compound N([C@@H](COC)C(=O)N[C@@H](COC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)[C@]1(C)OC1)C(=O)C1=CN=C(C)S1 SWZXEVABPLUDIO-WSZYKNRRSA-N 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
• IXOXBSCIXZEQEQ-UHTZMRCNSA-N nelarabine Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O IXOXBSCIXZEQEQ-UHTZMRCNSA-N 0.000 description 1
• 229960000801 nelarabine Drugs 0.000 description 1
• 230000001272 neurogenic effect Effects 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• 229960002715 nicotine Drugs 0.000 description 1
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
• 229960001420 nimustine Drugs 0.000 description 1
• VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
• OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
• 231100001143 noxa Toxicity 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 229960005554 obatoclax mesylate Drugs 0.000 description 1
• 238000006384 oligomerization reaction Methods 0.000 description 1
• 238000002966 oligonucleotide array Methods 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 229950005750 oprozomib Drugs 0.000 description 1
• 239000013307 optical fiber Substances 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 239000012663 orally bioavailable inhibitor Substances 0.000 description 1
• 229940044205 orally bioavailable inhibitor Drugs 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 229940045681 other alkylating agent in atc Drugs 0.000 description 1
• 229940045795 other cytotoxic antibiotic in ATC Drugs 0.000 description 1
• 229940045789 other plant alkaloid and natural product in atc Drugs 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 238000005895 oxidative decarboxylation reaction Methods 0.000 description 1
• 150000002924 oxiranes Chemical class 0.000 description 1
• 229960002239 paclitaxel poliglumex Drugs 0.000 description 1
• 108700027936 paclitaxel poliglumex Proteins 0.000 description 1
• 210000001819 pancreatic juice Anatomy 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
• 229940055729 papain Drugs 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 210000004912 pericardial fluid Anatomy 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 210000002824 peroxisome Anatomy 0.000 description 1
• 230000009038 pharmacological inhibition Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 229960000952 pipobroman Drugs 0.000 description 1
• NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 description 1
• 229960001221 pirarubicin Drugs 0.000 description 1
• 239000013600 plasmid vector Substances 0.000 description 1
• 150000003058 platinum compounds Chemical class 0.000 description 1
• 210000004910 pleural fluid Anatomy 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
• 239000003600 podophyllotoxin derivative Substances 0.000 description 1
• 238000003752 polymerase chain reaction Methods 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 238000010837 poor prognosis Methods 0.000 description 1
• 229960004293 porfimer sodium Drugs 0.000 description 1
• 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
• 229960000214 pralatrexate Drugs 0.000 description 1
• OGSBUKJUDHAQEA-WMCAAGNKSA-N pralatrexate Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CC(CC#C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OGSBUKJUDHAQEA-WMCAAGNKSA-N 0.000 description 1
• 229960004694 prednimustine Drugs 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 230000001686 pro-survival effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000002250 progressing effect Effects 0.000 description 1
• 208000037821 progressive disease Diseases 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 229960003910 promethazine Drugs 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 238000002331 protein detection Methods 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 230000005180 public health Effects 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000000163 radioactive labelling Methods 0.000 description 1
• 229960004432 raltitrexed Drugs 0.000 description 1
• 229960002185 ranimustine Drugs 0.000 description 1
• 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 1
• 238000003753 real-time PCR Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000022983 regulation of cell cycle Effects 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 238000011268 retreatment Methods 0.000 description 1
• 238000010839 reverse transcription Methods 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
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
• 229960000311 ritonavir Drugs 0.000 description 1
• 238000005096 rolling process Methods 0.000 description 1
• 108010091666 romidepsin Proteins 0.000 description 1
• 229960003452 romidepsin Drugs 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
• 102200111697 rs104894453 Human genes 0.000 description 1
• 102200152049 rs104894770 Human genes 0.000 description 1
• 102200061354 rs104894866 Human genes 0.000 description 1
• 102220032552 rs104895389 Human genes 0.000 description 1
• 102220194810 rs1057517606 Human genes 0.000 description 1
• 102200152078 rs1057520045 Human genes 0.000 description 1
• 102200149745 rs1057521103 Human genes 0.000 description 1
• 102220206928 rs1057521812 Human genes 0.000 description 1
• 102200104413 rs1060501202 Human genes 0.000 description 1
• 102200074788 rs111033567 Human genes 0.000 description 1
• 102200077165 rs118204021 Human genes 0.000 description 1
• 102200073080 rs119463988 Human genes 0.000 description 1
• 102200162761 rs128620184 Human genes 0.000 description 1
• 102200162820 rs128620185 Human genes 0.000 description 1
• 102200162818 rs128620189 Human genes 0.000 description 1
• 102200162849 rs128621190 Human genes 0.000 description 1
• 102200162840 rs128621194 Human genes 0.000 description 1
• 102200162723 rs128621196 Human genes 0.000 description 1
• 102200162705 rs128621198 Human genes 0.000 description 1
• 102200162742 rs128621200 Human genes 0.000 description 1
• 102200162744 rs128621202 Human genes 0.000 description 1
• 102200152272 rs128621203 Human genes 0.000 description 1
• 102200152048 rs128621204 Human genes 0.000 description 1
• 102200152070 rs128621206 Human genes 0.000 description 1
• 102200152011 rs128621208 Human genes 0.000 description 1
• 102200152010 rs128621209 Human genes 0.000 description 1
• 102200152109 rs128621210 Human genes 0.000 description 1
• 102200152132 rs128622212 Human genes 0.000 description 1
• 102200035386 rs137853120 Human genes 0.000 description 1
• 102200117384 rs13926 Human genes 0.000 description 1
• 102220206630 rs140636792 Human genes 0.000 description 1
• 102220081989 rs140796438 Human genes 0.000 description 1
• 102220015163 rs144152046 Human genes 0.000 description 1
• 102220257442 rs1445690889 Human genes 0.000 description 1
• 102220089504 rs144599870 Human genes 0.000 description 1
• 102220092500 rs145292219 Human genes 0.000 description 1
• 102220078390 rs147904927 Human genes 0.000 description 1
• 102220159983 rs150268016 Human genes 0.000 description 1
• 102220321823 rs1554812271 Human genes 0.000 description 1
• 102220326635 rs1555420162 Human genes 0.000 description 1
• 102220248763 rs1555781403 Human genes 0.000 description 1
• 102220332763 rs1555917318 Human genes 0.000 description 1
• 102200152047 rs1555977474 Human genes 0.000 description 1
• 102200162816 rs1555980875 Human genes 0.000 description 1
• 102220197676 rs1557036757 Human genes 0.000 description 1
• 102220309786 rs200117340 Human genes 0.000 description 1
• 102220100163 rs201567345 Human genes 0.000 description 1
• 102200071189 rs28934595 Human genes 0.000 description 1
• 102200162721 rs28935478 Human genes 0.000 description 1
• 102220340945 rs376480977 Human genes 0.000 description 1
• 102220229129 rs376675270 Human genes 0.000 description 1
• 102220083511 rs377620735 Human genes 0.000 description 1
• 102200050881 rs386833797 Human genes 0.000 description 1
• 102220012214 rs397515909 Human genes 0.000 description 1
• 102220029805 rs398123662 Human genes 0.000 description 1
• 102220018495 rs45509791 Human genes 0.000 description 1
• 102220093404 rs574202204 Human genes 0.000 description 1
• 102220024644 rs57877560 Human genes 0.000 description 1
• 102220044612 rs587781431 Human genes 0.000 description 1
• 102200058567 rs587782292 Human genes 0.000 description 1
• 102220135391 rs61750442 Human genes 0.000 description 1
• 102200142926 rs61752138 Human genes 0.000 description 1
• 102200022513 rs727502811 Human genes 0.000 description 1
• 102220056431 rs730880077 Human genes 0.000 description 1
• 102220056933 rs730880573 Human genes 0.000 description 1
• 102220056932 rs730880575 Human genes 0.000 description 1
• 102220242295 rs746383238 Human genes 0.000 description 1
• 102200091861 rs75709682 Human genes 0.000 description 1
• 102220242307 rs760486704 Human genes 0.000 description 1
• 102220169800 rs761985295 Human genes 0.000 description 1
• 102220021072 rs80356939 Human genes 0.000 description 1
• 102220117180 rs80357370 Human genes 0.000 description 1
• 102200128929 rs838827 Human genes 0.000 description 1
• 102220082272 rs863223860 Human genes 0.000 description 1
• 102200139137 rs864622780 Human genes 0.000 description 1
• 102220098772 rs878853359 Human genes 0.000 description 1
• 102220103922 rs878854913 Human genes 0.000 description 1
• 102200037645 rs879254535 Human genes 0.000 description 1
• 102200033553 rs886039231 Human genes 0.000 description 1
• 102220120553 rs886042598 Human genes 0.000 description 1
• 102220166430 rs886050759 Human genes 0.000 description 1
• 102220279469 rs992385562 Human genes 0.000 description 1
• 229950004707 rucaparib Drugs 0.000 description 1
• HMABYWSNWIZPAG-UHFFFAOYSA-N rucaparib Chemical compound C1=CC(CNC)=CC=C1C(N1)=C2CCNC(=O)C3=C2C1=CC(F)=C3 HMABYWSNWIZPAG-UHFFFAOYSA-N 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 229960005399 satraplatin Drugs 0.000 description 1
• 190014017285 satraplatin Chemical compound 0.000 description 1
• 108010049249 scytonemide A Proteins 0.000 description 1
• 210000000582 semen Anatomy 0.000 description 1
• 229960003440 semustine Drugs 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 235000015170 shellfish Nutrition 0.000 description 1
• 238000004904 shortening Methods 0.000 description 1
• 229960002930 sirolimus Drugs 0.000 description 1
• 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 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000000243 solution Substances 0.000 description 1
• 238000010911 splenectomy Methods 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 238000011301 standard therapy Methods 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 229960001052 streptozocin Drugs 0.000 description 1
• 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 description 1
• 238000005556 structure-activity relationship Methods 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 210000004243 sweat Anatomy 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229940066767 systemic antihistamines phenothiazine derivative Drugs 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960001674 tegafur Drugs 0.000 description 1
• WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
• 229960002197 temoporfin Drugs 0.000 description 1
• 229960004964 temozolomide Drugs 0.000 description 1
• 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 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
• 108091008743 testicular receptors 4 Proteins 0.000 description 1
• AUZONCFQVSMFAP-UHFFFAOYSA-N tetraethylthiuram disulfide Natural products CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 description 1
• 229960001196 thiotepa Drugs 0.000 description 1
• 229940113082 thymine Drugs 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• SYIKUFDOYJFGBQ-YLAFAASESA-N tofacitinib citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 SYIKUFDOYJFGBQ-YLAFAASESA-N 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 108091006107 transcriptional repressors Proteins 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 230000017105 transposition Effects 0.000 description 1
• 229960004560 triaziquone Drugs 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
• 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
• 229960000875 trofosfamide Drugs 0.000 description 1
• UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 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 description 1
• 229960000653 valrubicin Drugs 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 229950011257 veliparib Drugs 0.000 description 1
• JNAHVYVRKWKWKQ-CYBMUJFWSA-N veliparib Chemical compound N=1C2=CC=CC(C(N)=O)=C2NC=1[C@@]1(C)CCCN1 JNAHVYVRKWKWKQ-CYBMUJFWSA-N 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• 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 description 1
• 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 description 1
• 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 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• 229960004355 vindesine Drugs 0.000 description 1
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
• NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 description 1
• 229960000922 vinflunine Drugs 0.000 description 1
• GBABOYUKABKIAF-GHYRFKGUSA-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-GHYRFKGUSA-N 0.000 description 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 229940039916 xeljanz Drugs 0.000 description 1
• ZPUHVPYXSITYDI-HEUWMMRCSA-N xyotax Chemical compound OC(=O)[C@@H](N)CCC(O)=O.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 ZPUHVPYXSITYDI-HEUWMMRCSA-N 0.000 description 1