WO2009105936A1 - 苯酚苷衍生物在制备抗细胞增生疾病组合物中的应用 - Google Patents
苯酚苷衍生物在制备抗细胞增生疾病组合物中的应用 Download PDFInfo
- Publication number
- WO2009105936A1 WO2009105936A1 PCT/CN2008/070373 CN2008070373W WO2009105936A1 WO 2009105936 A1 WO2009105936 A1 WO 2009105936A1 CN 2008070373 W CN2008070373 W CN 2008070373W WO 2009105936 A1 WO2009105936 A1 WO 2009105936A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cancer
- group
- cell
- etoposide
- retinoic acid
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 33
- 239000000203 mixture Substances 0.000 title claims abstract description 33
- 201000010099 disease Diseases 0.000 title claims abstract description 24
- 230000004663 cell proliferation Effects 0.000 title claims abstract description 9
- 229930182487 phenolic glycoside Natural products 0.000 title abstract description 40
- 150000007950 phenolic glycosides Chemical class 0.000 title abstract description 40
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 239000003814 drug Substances 0.000 claims abstract description 38
- 230000002159 abnormal effect Effects 0.000 claims abstract description 12
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 41
- 150000001875 compounds Chemical class 0.000 claims description 36
- -1 hydroxy, hydroxymethyl Chemical group 0.000 claims description 32
- 229940079593 drug Drugs 0.000 claims description 30
- 230000002062 proliferating effect Effects 0.000 claims description 28
- 230000003902 lesion Effects 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
- 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 23
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 23
- 229960002066 vinorelbine Drugs 0.000 claims description 19
- 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 claims description 19
- 230000001594 aberrant effect Effects 0.000 claims description 18
- 229960004316 cisplatin Drugs 0.000 claims description 18
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 18
- 229960005420 etoposide Drugs 0.000 claims description 18
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 17
- 239000002246 antineoplastic agent Substances 0.000 claims description 17
- 229930002330 retinoic acid Natural products 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 15
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 15
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 15
- 229940041181 antineoplastic drug Drugs 0.000 claims description 15
- 229940022353 herceptin Drugs 0.000 claims description 15
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 claims description 14
- 229930105110 Cyclosporin A Natural products 0.000 claims description 14
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 14
- 108010036949 Cyclosporine Proteins 0.000 claims description 14
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 14
- 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 14
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 14
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 claims description 14
- 229960002949 fluorouracil Drugs 0.000 claims description 14
- 229960003048 vinblastine Drugs 0.000 claims description 14
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 14
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 13
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 13
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 12
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims description 12
- 201000007270 liver cancer Diseases 0.000 claims description 12
- 208000014018 liver neoplasm Diseases 0.000 claims description 12
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 12
- 229960001196 thiotepa Drugs 0.000 claims description 12
- 229960001727 tretinoin Drugs 0.000 claims description 12
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 12
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 11
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 11
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 11
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 11
- 229960003787 sorafenib Drugs 0.000 claims description 11
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
- 229960002756 azacitidine Drugs 0.000 claims description 10
- 229960004679 doxorubicin Drugs 0.000 claims description 10
- 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 claims description 10
- 229960001972 panitumumab Drugs 0.000 claims description 10
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims description 10
- 229960004964 temozolomide Drugs 0.000 claims description 10
- 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 9
- 229960004891 lapatinib Drugs 0.000 claims description 9
- 239000002243 precursor Substances 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
- 229960004942 lenalidomide Drugs 0.000 claims description 8
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims description 8
- 229960001796 sunitinib Drugs 0.000 claims description 8
- 229960003433 thalidomide Drugs 0.000 claims description 8
- GPVGDGBVGWUGAL-UHFFFAOYSA-N 1-cyclohexyl-1-nitrosourea Chemical compound NC(=O)N(N=O)C1CCCCC1 GPVGDGBVGWUGAL-UHFFFAOYSA-N 0.000 claims description 7
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 7
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 7
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 7
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 7
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 claims description 7
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 claims description 7
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 7
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 7
- 239000002067 L01XE06 - Dasatinib Substances 0.000 claims description 7
- 229930192392 Mitomycin Natural products 0.000 claims description 7
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 claims description 7
- 229940120638 avastin Drugs 0.000 claims description 7
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 7
- 229960004562 carboplatin Drugs 0.000 claims description 7
- 229960005243 carmustine Drugs 0.000 claims description 7
- 229960004630 chlorambucil Drugs 0.000 claims description 7
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 7
- 229960004397 cyclophosphamide Drugs 0.000 claims description 7
- 229960005277 gemcitabine Drugs 0.000 claims description 7
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 7
- 229940080856 gleevec Drugs 0.000 claims description 7
- 229960001330 hydroxycarbamide Drugs 0.000 claims description 7
- 229940084651 iressa Drugs 0.000 claims description 7
- 229960001924 melphalan Drugs 0.000 claims description 7
- 229960000485 methotrexate Drugs 0.000 claims description 7
- 229960004857 mitomycin Drugs 0.000 claims description 7
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 7
- 229960004866 mycophenolate mofetil Drugs 0.000 claims description 7
- 150000003431 steroids Chemical class 0.000 claims description 7
- 229960001052 streptozocin Drugs 0.000 claims description 7
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims description 7
- 229960003087 tioguanine Drugs 0.000 claims description 7
- 229940053867 xeloda Drugs 0.000 claims description 7
- 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 claims description 6
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 6
- 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 claims description 6
- 108010006654 Bleomycin Proteins 0.000 claims description 6
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 6
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 6
- 108010092160 Dactinomycin Proteins 0.000 claims description 6
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 6
- QZHBYJZCGCZMDC-UHFFFAOYSA-N OC=1C(C2=CC3=CC=CC=C3C2=CC1O)=O Chemical compound OC=1C(C2=CC3=CC=CC=C3C2=CC1O)=O QZHBYJZCGCZMDC-UHFFFAOYSA-N 0.000 claims description 6
- 229930012538 Paclitaxel Natural products 0.000 claims description 6
- 229930183665 actinomycin Natural products 0.000 claims description 6
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 6
- 229960001561 bleomycin Drugs 0.000 claims description 6
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 6
- 229960004117 capecitabine Drugs 0.000 claims description 6
- 229960000684 cytarabine Drugs 0.000 claims description 6
- 229960003603 decitabine Drugs 0.000 claims description 6
- 229960001904 epirubicin Drugs 0.000 claims description 6
- 229940111707 ixempra Drugs 0.000 claims description 6
- 229960001592 paclitaxel Drugs 0.000 claims description 6
- 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 6
- 229940063683 taxotere Drugs 0.000 claims description 6
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 6
- 229960004528 vincristine Drugs 0.000 claims description 6
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 6
- 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 claims description 6
- 229960004355 vindesine Drugs 0.000 claims description 6
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 claims description 5
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 5
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 5
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 5
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 5
- 229960000975 daunorubicin Drugs 0.000 claims description 5
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229940082789 erbitux Drugs 0.000 claims description 5
- 206010017758 gastric cancer Diseases 0.000 claims description 5
- 229960000908 idarubicin Drugs 0.000 claims description 5
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 5
- 229960004768 irinotecan Drugs 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 229960002247 lomustine Drugs 0.000 claims description 5
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 5
- 229960001156 mitoxantrone Drugs 0.000 claims description 5
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 5
- 229960001756 oxaliplatin Drugs 0.000 claims description 5
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 5
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 5
- 229960000624 procarbazine Drugs 0.000 claims description 5
- 201000011549 stomach cancer Diseases 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 5
- 229960000303 topotecan Drugs 0.000 claims description 5
- 229940100411 torisel Drugs 0.000 claims description 5
- HDCUSMZVZWLDRZ-UHFFFAOYSA-N 1-benzyl-2-methylhydrazine Chemical compound CNNCC1=CC=CC=C1 HDCUSMZVZWLDRZ-UHFFFAOYSA-N 0.000 claims description 4
- HDBQZGJWHMCXIL-UHFFFAOYSA-N 3,7-dihydropurine-2-thione Chemical compound SC1=NC=C2NC=NC2=N1 HDBQZGJWHMCXIL-UHFFFAOYSA-N 0.000 claims description 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 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 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 201000004101 esophageal cancer Diseases 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 229960001101 ifosfamide Drugs 0.000 claims description 4
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 230000035407 negative regulation of cell proliferation Effects 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 229960004432 raltitrexed Drugs 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229960001265 ciclosporin Drugs 0.000 claims description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
- 229960002448 dasatinib Drugs 0.000 claims description 3
- 230000000069 prophylactic effect Effects 0.000 claims description 3
- 229960004641 rituximab Drugs 0.000 claims description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
- 150000001299 aldehydes Chemical class 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims 3
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- 241000186361 Actinobacteria <class> Species 0.000 claims 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- 241000009298 Trigla lyra Species 0.000 claims 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims 1
- 229960000623 carbamazepine Drugs 0.000 claims 1
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 claims 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 229920005610 lignin Polymers 0.000 claims 1
- 210000005075 mammary gland Anatomy 0.000 claims 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 claims 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims 1
- 229940102566 valproate Drugs 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 65
- 229930182470 glycoside Natural products 0.000 description 19
- 239000002904 solvent Substances 0.000 description 18
- 238000011282 treatment Methods 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 206010020718 hyperplasia Diseases 0.000 description 15
- 210000001700 mitochondrial membrane Anatomy 0.000 description 12
- 230000034994 death Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 8
- 206010054949 Metaplasia Diseases 0.000 description 8
- 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 description 8
- 238000000605 extraction Methods 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000030833 cell death Effects 0.000 description 6
- 229960003668 docetaxel Drugs 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- 208000009905 Neurofibromatoses Diseases 0.000 description 5
- 210000003679 cervix uteri Anatomy 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 208000002741 leukoplakia Diseases 0.000 description 5
- 230000002438 mitochondrial effect Effects 0.000 description 5
- 201000004931 neurofibromatosis Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 4
- 208000004300 Atrophic Gastritis Diseases 0.000 description 4
- 206010008909 Chronic Hepatitis Diseases 0.000 description 4
- 206010010356 Congenital anomaly Diseases 0.000 description 4
- VFZRZRDOXPRTSC-UHFFFAOYSA-N DMBA Natural products COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 208000036495 Gastritis atrophic Diseases 0.000 description 4
- 206010018338 Glioma Diseases 0.000 description 4
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 4
- 108010067028 Mitochondrial Permeability Transition Pore Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229960000397 bevacizumab Drugs 0.000 description 4
- 229960001467 bortezomib Drugs 0.000 description 4
- 229960005395 cetuximab Drugs 0.000 description 4
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 4
- 230000007882 cirrhosis Effects 0.000 description 4
- 208000019425 cirrhosis of liver Diseases 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229960002584 gefitinib Drugs 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 4
- 229960002014 ixabepilone Drugs 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- DHMTURDWPRKSOA-RUZDIDTESA-N lonafarnib Chemical compound C1CN(C(=O)N)CCC1CC(=O)N1CCC([C@@H]2C3=C(Br)C=C(Cl)C=C3CCC3=CC(Br)=CN=C32)CC1 DHMTURDWPRKSOA-RUZDIDTESA-N 0.000 description 4
- 229950001750 lonafarnib Drugs 0.000 description 4
- 230000015689 metaplastic ossification Effects 0.000 description 4
- 210000000214 mouth Anatomy 0.000 description 4
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 4
- 229940080607 nexavar Drugs 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 229940120975 revlimid Drugs 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 229940068117 sprycel Drugs 0.000 description 4
- 229940034785 sutent Drugs 0.000 description 4
- 229940120982 tarceva Drugs 0.000 description 4
- 229940061353 temodar Drugs 0.000 description 4
- 229960000235 temsirolimus Drugs 0.000 description 4
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 4
- PLHJCIYEEKOWNM-HHHXNRCGSA-N tipifarnib Chemical compound CN1C=NC=C1[C@](N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 PLHJCIYEEKOWNM-HHHXNRCGSA-N 0.000 description 4
- 229950009158 tipifarnib Drugs 0.000 description 4
- 229960000575 trastuzumab Drugs 0.000 description 4
- 229940099039 velcade Drugs 0.000 description 4
- 210000003905 vulva Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000006285 cell suspension Substances 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
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000002357 endometrial effect Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 208000029824 high grade glioma Diseases 0.000 description 3
- 201000011614 malignant glioma Diseases 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 208000014081 polyp of colon Diseases 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 208000032589 Diaphragmatic Congenital Hernias Diseases 0.000 description 2
- 206010058314 Dysplasia Diseases 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
- 241000305491 Gastrodia elata Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000218682 Pseudolarix amabilis Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 208000028183 atypical endometrial hyperplasia Diseases 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 201000005890 congenital diaphragmatic hernia Diseases 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000006667 mitochondrial pathway Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 150000007965 phenolic acids Chemical class 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 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
- 239000012588 trypsin Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 229940094060 tykerb Drugs 0.000 description 2
- NUXWXMZVAHSICO-YCNIQYBTSA-N (2e,4e,6e,8e)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenamide Chemical compound NC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NUXWXMZVAHSICO-YCNIQYBTSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- JVYDLYGCSIHCMR-UHFFFAOYSA-N 2,2-bis(hydroxymethyl)butanoic acid Chemical compound CCC(CO)(CO)C(O)=O JVYDLYGCSIHCMR-UHFFFAOYSA-N 0.000 description 1
- RNIPJYFZGXJSDD-UHFFFAOYSA-N 2,4,5-triphenyl-1h-imidazole Chemical compound C1=CC=CC=C1C1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 RNIPJYFZGXJSDD-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
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010062877 Bacteriocins Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 241000219198 Brassica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 240000001008 Dimocarpus longan Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010049678 Endometrial dysplasia Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 235000000235 Euphoria longan Nutrition 0.000 description 1
- 241000975394 Evechinus chloroticus Species 0.000 description 1
- 208000000571 Fibrocystic breast disease Diseases 0.000 description 1
- 206010016717 Fistula Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 241001648385 Helicia Species 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 240000007695 Nandina domestica Species 0.000 description 1
- 208000007256 Nevus Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000004179 Oral Leukoplakia Diseases 0.000 description 1
- 101710129178 Outer plastidial membrane protein porin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102100037820 Voltage-dependent anion-selective channel protein 1 Human genes 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- WMWLMWRWZQELOS-UHFFFAOYSA-N bismuth(III) oxide Inorganic materials O=[Bi]O[Bi]=O WMWLMWRWZQELOS-UHFFFAOYSA-N 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 208000011803 breast fibrocystic disease Diseases 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 210000000621 bronchi Anatomy 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
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 206010008323 cervicitis Diseases 0.000 description 1
- 230000002113 chemopreventative effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 201000003988 chronic cervicitis Diseases 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000003947 ethylamines Chemical class 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 125000004383 glucosinolate group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 102000054896 human PML Human genes 0.000 description 1
- 150000004677 hydrates Chemical class 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
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 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
- 230000036212 malign transformation Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 150000003956 methylamines Chemical class 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 230000019735 mitochondria-nucleus signaling pathway Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 201000008557 oral mucosa leukoplakia Diseases 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000004686 pentahydrates Chemical class 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 208000015768 polyposis Diseases 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 229960003876 ranibizumab Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229940100552 retinamide Drugs 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/282—Platinum compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the invention belongs to the field of medicine; relates to the use of a class of phenolic glycoside derivatives, which can be used alone or in combination with other drugs for the prevention and treatment of abnormal cell proliferative diseases.
- Cellular aberrant proliferative disease refers to a disorder caused by abnormal proliferation, differentiation and death of cells under pathological conditions, resulting in abnormal growth of cells, including precancerous lesions, tumors (malignant tumors or benign tumors), Myloprol iferative disorders (MDS), congenital fistula (Congenital Nevi) and neurofibromatosis (neurofibromatosis) and other types.
- precancerous lesions tumors (malignant tumors or benign tumors), Myloprol iferative disorders (MDS), congenital fistula (Congenital Nevi) and neurofibromatosis (neurofibromatosis) and other types.
- MDS Myloprol iferative disorders
- congenital fistula Congenital Nevi
- neurofibromatosis neurofibromatosis
- cancer malignant tumors
- anticancer drugs have been used in clinical treatment, most drugs can only relieve the disease, and most tumors, especially solid tumors, have very limited chemotherapy effects.
- countries have invested a lot of manpower and material resources in the research and development of anticancer drugs, hoping to have more anticancer drugs for clinical use.
- Precancerous lesions refer to the sustained action of somatic cells due to carcinogenic factors.
- the nucleus and chromosomes are abnormally deformed and reflected in the change of cell morphology. This is also the pathologist often looks at the slices.
- One of the cell lesions One of the cell lesions.
- Precancerous lesions can occur in different parts, including severe epithelial hyperplasia, gastric atypical hyperplasia, intestinal metaplasia and atrophic gastritis, chronic hepatitis and cirrhosis, chronic cervicitis, fibrocystic breast disease, colonic multiple Polyps, bronchial epithelial hyperplasia and metaplasia, leukoplakia such as oral cavity, cervix and vulva, atypical hyperplasia of the endometrium.
- the main feature of "precancerous lesions” is the disappearance of cell polarity, heterotypic, according to the degree of hyperplasia can be divided into light, moderate, severe, but no interstitial infiltration.
- Precancerous lesions usually develop into invasive cancers in situ for many years. For example, foreign studies suggest that about 23% of endometrial dysplasia develops into cancer after 10 years, while domestic studies have found endometrial atypical hyperplasia. 82% of the year will develop into invasive cancer. "Precancerous lesions” are usually reversible. If the lesions progress to invasive cancer, the incidence and mortality of malignant tumors can be effectively reduced.
- ⁇ -cis retinoic acid for example, clinical use of ⁇ -cis retinoic acid to prevent the occurrence of a second type of primary cancer in patients with head and neck cancer, treatment of oral leukoplakia, leukoplakia, cervix and gastric mucosal dysplasia and other precancerous lesions with retinoic acid, Affirmative results have been achieved.
- Myelodysplastic syndrome is a malignant blood disease that originates from the hematopoietic myeloid stem cells or more
- the heterogeneous clonal disorder of stem cells is characterized by ineffective hematopoiesis and high-risk evolution into acute myeloid leukemia.
- the clinical manifestations are abnormal changes in the quality and quantity of hematopoietic cells.
- the treatment of this disease urgently requires a cure for the disease rather than just controlling the symptoms, but the drugs used to treat MDS are only a few drugs such as 5-azacitidine and Revl imid.
- MPTP mitochondrial permeability transition pore
- ANT adenylate transposon
- He XO kina Se hexokinase
- VDAC voltage-dependent ion channel
- mPBR peripheral benzocdiazepine receptor
- mPBR is abnormally highly expressed in a variety of tumors such as liver cancer, lung cancer, prostate cancer, glioblastoma and gastric cancer, and regulation of mPBR activity can down-regulate tumor cell apoptosis threshold. Therefore, mPBR ligand is a new molecular target for the development of anti-tumor drugs.
- a compound of formula (I) or an isomer, racemate, precursor or pharmaceutically acceptable salt thereof for the prophylaxis or treatment of abnormal cell proliferation a composition of a sexual disease;
- R1, R2, R3, R4 or R5 independently represent hydrogen, hydroxy, hydroxymethyl, aldehyde, nitro, propionyl halogen atom, aminomethyl, acryloyl, hydroxyimino, C1-C8 alkyl, C2 -C8 alkenyl, a C2-C8 block group, a C3-C8 cyclodecyl group, a C3-C8 cycloalkenyl group, a C1-C8 alkoxy group or a C1-C4 carboxyl group;
- R6 represents (C)tician0H, wherein n represents a positive selected from 1-3 Integer.
- the compound is selected from the group consisting of
- the compound is selected from the group consisting of: (S7), (S8),
- the compound is Sl-S5.
- the cell aberrant proliferative disorder is selected from, but not limited to, a tumor (malignant tumor or benign tumor), myloproliferative disorders (MDS) or precancerous lesions.
- a tumor malignant tumor or benign tumor
- MDS myloproliferative disorders
- the tumor is selected from the group consisting of, but not limited to, non-small cell lung cancer, liver cancer, brain tumor, leukemia, prostate cancer, colorectal cancer, pancreatic cancer, myeloma, lymphoma, breast cancer, ovary Cancer, gastric cancer, small cell lung cancer, esophageal cancer, head and neck cancer or sarcoma.
- the precancerous lesion is selected from (but not limited to): severe epithelial hyperplasia, atypical hyperplasia of the gastric mucosa, intestinal metaplasia, atrophic gastritis, chronic hepatitis, cirrhosis, colon polyps, bronchi Epithelial hyperplasia or metaplasia, leukoplakia (such as in the mouth, cervix, vulva, etc.), endometrial atypical hyperplasia, congenital diaphragmatic or neurofibromatosis.
- the composition is further for increasing the efficacy of an antitumor drug selected from the group consisting of, but not limited to, doxorubicin; vincristine; vinorelbine; paclitaxel; cisplatin; Actinomycin; bleomycin; busulfan; capecitabine; carboplatin; carmustine; chlorambucil; cyclophosphamide; cytarabine; daunorubicin; Etoposide; etoposide; etoposide; glucosinolate; fluoroarabinoside; fluorouracil; gemcitabine; Herceptin; hydroxyurea; idarubicin; ifosfamide; irinote Kang; lomustine; cyclohexyl nitrosourea; melphalan; L-phenylalanine mustard; thiopurine; methotrexate; mitomycin; mitoxantrone; dihydroxy fluoren
- composition is also useful for increasing the efficacy of a drug selected from the group consisting of, but not limited to, anti-myeloproliferative diseases: azacitidine (azacitidine); decitabine (Decitabine) ); Mycophenolate Mofetil; cyclosporine A; ⁇ 3 ⁇ 4 ⁇ Lonafarnib; Tipifarnib; arsenic trioxide; lenalidomide
- a drug selected from the group consisting of, but not limited to, anti-myeloproliferative diseases: azacitidine (azacitidine); decitabine (Decitabine) ); Mycophenolate Mofetil; cyclosporine A; ⁇ 3 ⁇ 4 ⁇ Lonafarnib; Tipifarnib; arsenic trioxide; lenalidomide
- composition is also useful for increasing the efficacy of an anti-cancer drug selected from the group consisting of, but not limited to, ⁇ -cis retinoic acid; retinoic acid; non-alcoholic anti-inflammatory drugs; or their derivatives Or a mixture.
- an anti-cancer drug selected from the group consisting of, but not limited to, ⁇ -cis retinoic acid; retinoic acid; non-alcoholic anti-inflammatory drugs; or their derivatives Or a mixture.
- the antitumor drug is selected from the group consisting of: cisplatin (CDDP), docetaxel (DXT), temozolomide, sorafenib, cyclosporine A (CsA), doxorubicin (ADR) ), vinorelbine (VNB), trans-retinoic acid (ATRA).
- composition for preventing or treating a cell aberrant proliferative disorder comprising:
- the drug for anti-cell aberrant proliferative disease is selected from, but not limited to, doxorubicin; vincristine; vinorelbine; paclitaxel; cisplatin; actinomycin; Bacteriocin; busulfan; carboplatin; carmustine; chlorambucil; cyclophosphamide; cytarabine; daunorubicin; epirubicin; etoposide; Ye Yiqi; scorpion scorpion; fluoroarabinoside; fluorouracil; gemcitabine; Herceptin; hydroxyurea; idarubicin; ifosfamide; irinotecan; lomustine; Cyclohexyl nitrosourea; melphalan; L-phenylalanine; mustard; methotrexate; mitomycin; mitoxantrone; dihydroxy fluorenone; oxaliplatin; Methyl benzyl hydrazine; Rit
- a method for inhibiting abnormal cell proliferation comprising: administering to a subject in need of inhibition of cell proliferation an effective amount of a compound of the formula (I) or an isomer thereof, exogenous A spiro, precursor or pharmaceutically acceptable salt.
- the method is performed in vitro (e.g., non-therapeutic).
- the method further comprises: administering to the subject in need of inhibition of cell proliferation an effective amount of a drug selected from, but not limited to, the group of anti-cell aberrant proliferative diseases: doxorubicin; vincristine; Vinorelbine; paclitaxel; cisplatin; actinomycin; bleomycin; busulfan; capecitabine; carboplatin; carmustine; chlorambucil; cyclophosphamide; ; daunorubicin; epirubicin; etoposide; etoposide; etoposide; fluoroarabinoside; fluorouracil; gemcitabine; Herceptin; hydroxyurea; Star; ifosfamide; irinotecan; lomustine; cyclohexyl nitrosourea; melphalan; L-phenylalanine mustard; thiopurine; methotrexate; mitomycin; Dihydroxy fluorenone; o
- the compound when the subject is administered to a mammal, is administered at a dose of 0. l-500 mg/kg body weight (more preferably 1-200 mg/kg body weight; further preferably 1-100 mg/kg body weight).
- Figure 1 shows the inhibitory effect of the phenolic glycoside derivative S1-S5 on the proliferation of human malignant glioma cell line U87-MG.
- Figure 2 shows that the phenolic glycoside derivative S2-S5 is used in combination with other antitumor drugs to induce mitochondrial pathway cell death.
- Figure 2A shows S2 5 (g/ml concentration alone and in combination with doxorubicin (ADR) g/ml concentration induced mitochondrial membrane potential decline and death in human liver cancer HuH-7 cells.
- Figure 2B shows S3 8 (g/ The concentration of ml alone and cisplatin (CDDP) 5 (g/ml combined to induce mitochondrial membrane potential decline and death in human prostate cancer Du-145 cells.
- ADR doxorubicin
- CDDP cisplatin
- FIG. 2C shows S4 5 ( ⁇ g / ml concentration of single drug and with Changchun The combination of rubbins (VNB) reduces mitochondrial membrane potential and death in human non-small cell lung cancer H1299 cells.
- Figure 2D shows that S5 4 (g/ml concentration alone and in combination with all-trans retinoic acid (ATRA) makes early childhood Granulocyte leukemia cells have a decreased mitochondrial membrane potential and death.
- ATRA all-trans retinoic acid
- Figure 3 shows that the phenolic glycoside derivative S1 inhibits the binding of 3 ⁇ 4-PK11 195 to mPBR.
- Figure 4 shows that the phenolic glycoside derivative S1 alone has a certain degree of inhibition on the growth of Huh-7 human hepatocellular carcinoma xenografts. When used in combination with cisplatin (CDDP), the antitumor effect is significantly greater than that of monotherapy.
- CDDP cisplatin
- Figure 5 shows that the phenol glycoside derivative S2 alone and in combination with docetaxel (DXT) inhibits the growth of SPC-A-1 human non-small cell lung cancer xenograft tumors.
- DXT docetaxel
- Figure 6 shows the inhibition of the phenolic glycoside derivative S3 alone and in combination with temozolomide (TMZ).
- Figure 7 shows that the phenolic glycoside derivative S4 alone and in combination with cisplatin (CDDP) inhibits the growth of SPC-A-1 human non-small cell lung cancer xenograft tumors.
- Figure 8 shows that the phenolic glycoside derivative S5 alone and in combination with sorafenib inhibited the growth of Bel-7402 human liver cancer xenograft tumors.
- FIG. 9 shows that the phenolic glycoside derivative S1-S5 alone and in combination with cyclosporin A (CsA) induces fresh MDS cell death.
- alkyl refers to a saturated, straight or branched aliphatic hydrocarbon group (preferably
- alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl.
- alkenyl denotes a straight or branched chain hydrocarbon radical containing at least one carbon-carbon double bond and at least 2 carbon atoms, preferably 2-8 carbon atoms, more preferably 2-4.
- alkynyl denotes straight-chain and branched hydrocarbon radicals containing at least one carbon-carbon triple bond and at least 2 carbon atoms, preferably 2-8 carbon atoms, more preferably 2-4.
- halogen refers to F, Cl, Br or I, especially F, C1 or Br.
- alkoxy refers to an alkyl group as described above containing oxygen, such as methoxy, ethoxy, n-propoxy, isopropoxy and the like.
- cycloalkyl refers to a cycloalkyl group having 3 to 8 carbon atoms such as a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and the like.
- cycloalkenyl as used herein is defined as “cycloalkyl” and contains at least one unsaturated carbon-carbon double bond.
- isomer as used herein includes: conformational isomers, optical isomers (e.g., enantiomers and diastereomers), geometric isomers (e.g., cis and trans isomers).
- the present invention first provides a compound of formula (I):
- R1, R2, R3, R4, R5 or R6 are as defined in claim 1.
- the compound is represented by the formula ( ⁇ ) or (I I I):
- the present invention also includes isomers, racemates, pharmaceutically acceptable salts, hydrates or precursors of the above compounds.
- the "pharmaceutically acceptable salt” means a salt formed by reacting a compound of the formula (I) with an inorganic acid, an organic acid, an alkali metal or an alkaline earth metal or the like.
- These salts include, but are not limited to: (1) with the following inorganic acid forms Salts: such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid; (2) salts with the following organic acids, such as acetic acid, lactic acid, citric acid, succinic acid, fumaric acid, gluconic acid, benzoic acid , maleic acid, or arginine.
- salts include those formed with alkali or alkaline earth metals such as sodium, potassium, calcium or magnesium, ammonium or water-soluble amine salts such as N-methylglucamine salts, and lower alkanolammonium salts.
- alkali or alkaline earth metals such as sodium, potassium, calcium or magnesium
- ammonium or water-soluble amine salts such as N-methylglucamine salts, and lower alkanolammonium salts.
- other pharmaceutically acceptable amine salts such as methylamine salts, ethylamine salts, propylamine salts, dimethylamine salts
- the compound has one or more asymmetric centers. Therefore, these compounds may exist as racemic mixtures, individual enantiomers, individual diastereomers, diastereomeric mixtures, cis or trans isomers.
- precursor of a compound refers to a compound of formula (I), or a compound of formula (I), which is metabolized or chemically reacted in a patient's body after administration by an appropriate method.
- a pharmaceutical extract containing the compound of the present invention as an active ingredient is also included in the present invention.
- the compounds of the present invention can be obtained by various methods well known in the art, using known starting materials, such as chemical synthesis or extraction from plants, all of which are included in the present invention. In the invention.
- the starting materials used to prepare the compounds of the present invention or intermediates thereof are known in the art or are commercially available unless otherwise stated or provided.
- the phenol glycoside derivative S 1 can be obtained by a chemical extraction method from the traditional Chinese medicine Gastrodia elata.
- the phenolic glycoside derivatives S2 and S3 can be obtained by chemical extraction from the traditional Chinese medicine Pseudolarix kaempferi.
- the phenol glycoside derivative S4 can be obtained by chemical extraction from the plant of the genus Longan (Hel i c ia Lour.).
- the phenol glycoside derivative S5 can be obtained by chemical synthesis in combination with microbial transformation.
- the present invention provides the use of a compound of the formula (I) or an isomer, a racemate, a precursor or a pharmaceutically acceptable salt thereof for the preparation of a prophylactic or therapeutic cell abnormality A composition of a proliferative disease.
- the mechanism of action of the phenolic glycoside derivatives of the present invention is: by acting on the mitochondrial benzodiazepine (mPBR) receptor, the mitochondrial membrane potential is decreased, the mitochondrial membrane permeability is increased, and the cell death threshold is lowered. Therefore, it has a broad spectrum of activity against cell aberrant proliferative diseases.
- the cell aberrant proliferative diseases include, but are not limited to, tumors (malignant tumors or benign tumors), myeloproliferative diseases or precancerous lesions.
- the phenol glycoside derivatives have effects on a broad spectrum of tumors, some examples of which are (but not limited to): non-small cell lung cancer, liver cancer, brain tumor, leukemia, prostate cancer, colorectal cancer, pancreatic cancer, Myeloma, lymphoma, breast cancer, ovarian cancer, gastric cancer, small cell lung cancer, esophageal cancer, head and neck cancer or sarcoma.
- precancerous lesions include severe epithelial hyperplasia, atypical hyperplasia of the gastric mucosa, intestinal metaplasia, atrophic gastritis, Chronic hepatitis, cirrhosis, colon polyps, bronchial epithelial hyperplasia or metaplasia, leukoplakia (such as in the mouth, cervix, vulva, etc.), endometrial atypical hyperplasia, congenital diaphragmatic or neurofibromatosis.
- the present inventors have unexpectedly discovered that the phenol glycoside derivative can also be used to increase the efficacy of many antitumor drugs, antimyeloproliferative drugs, anticancer drugs, and thus can be used as sensitizers. Or synergist.
- the phenol glycoside derivative of the present invention can be used alone or in combination with other tumor therapeutic drugs and tumor treatment methods.
- the tumor treatment methods are, for example, surgery, chemotherapy, radiation therapy, and biological therapy. combination
- the present invention also encompasses a pharmaceutical composition
- a pharmaceutical composition comprising the phenolic glycoside derivative of the formula (I) of the present invention as an active ingredient together with one or more pharmaceutically acceptable carriers or excipients (e.g., a solvent, a diluent).
- pharmaceutically acceptable carriers useful in the present invention include various conventional solid carriers and liquid carriers.
- solid carriers include: starch, lactose, calcium hydrogen phosphate, microcrystalline cellulose, and the like
- the liquid carrier includes: sterile water, polyethylene glycol, and the like, as long as it is suitable for the characteristics of the active ingredient and the particular mode of administration desired.
- compositions of the present invention can be formulated into various conventional forms, for example: tablets, capsules, dispersible powders, granules or suspensions, syrups (containing, for example, about 10-50% sugar), and elixirs (containing about 20- Parenteral administration is carried out in the form of a sterile injectable solution or suspension (containing about 0.05 to 5% of a suspending agent in an isotonic medium).
- these pharmaceutical preparations may contain from about 0.01 to 99. 9 wt%, preferably from 2. 5 to 90 wt%, more preferably from 5 to 60 wt% of the phenol glycoside derivative, mixed with the carrier.
- Another preferred pharmaceutical composition also contains other anti-cell aberrant proliferative drugs, such as other anti-cell aberrant proliferative drugs such as:
- An anti-tumor drug selected from the group consisting of (but not limited to): doxorubicin; vincristine; vinorelbine; yew Alcohol; cisplatin; actinomycin; bleomycin; busulfan; capecitabine; carboplatin; carmustine; chlorambucil; cyclophosphamide; cytarabine; Epirubicin; etoposide; etoposide; etoposide; fluoroarabinoside; fluorouracil; gemcitabine; Herceptin; hydroxyurea; idarubicin; Phosphoramide; irinotecan; lomustine; cyclohexyl nitrosourea; melphalan; L-phenylalanine mustard; sulfhydryl; methotrexate; mitomycin; mitoxantrone; Anthrone; oxaliplatin; procarbazine; methyl benzyl hydrazin
- An anti-myeloproliferative drug selected from the group consisting of, but not limited to, azacitidine (azacitidine); decitabine; Mycophenolate Mofetil; Cyclosporine A; ⁇ , Lonafarnib; Tipifarnib; arsenic trioxide; lenalidomide/Levl imid; thalidomide; or Derivatives or mixtures thereof;
- Efficacy of a drug selected from the group consisting of, but not limited to, an anti-cancer drug: ⁇ -cis retinoic acid; retinoic acid; a non-sterol anti-inflammatory drug; or a derivative or mixture thereof.
- the composition may contain (a) 0.01 to 99% by weight (preferably 0.1 to 90% by weight) of the phenol glycoside derivative; (b) 0.01 to 99% by weight (preferably 0.1 to 90% by weight) An anti-cell aberrant proliferative drug; and (c) a pharmaceutically acceptable carrier.
- the weight ratio of the component (a) to the component (b) is 1:100 to 100:1, more preferably 10:1 to 1:10.
- the pharmaceutical composition may also contain other additives such as anti-pigments, preservatives and antioxidants.
- the effective dose of the active ingredient employed will vary with the dosage regimen and the severity of the condition being treated. However, usually, when the phenol glycoside derivative is administered at a dose of about 0.1 to 500 mg/kg body weight per day (preferably 1 to 200 mg/kg body weight; more preferably 1 to 100 mg/kg body weight), Satisfactory effect, It is preferably administered in 1-3 divided doses or in sustained release form. treatment method
- the invention also provides a method of treatment comprising the steps of: administering a safe and effective amount of a phenol glycoside derivative to a subject in need of treatment, such as a mammal, or a cell.
- the method further comprises the step of: simultaneously combining other drugs or other treatment means (such as radiotherapy).
- Single or combined phenolic glycoside derivatives can treat a variety of different cell aberrant proliferative diseases, especially precancerous lesions or tumors.
- Representative examples include (but are not limited to): lung cancer, liver cancer, brain tumor, pancreatic cancer , leukemia, prostate cancer, gastric cancer, esophageal cancer, colon cancer, myeloma, lymphoma, breast cancer, ovarian cancer, colon cancer, sarcoma, etc.
- precancerous lesions include severe epithelial hyperplasia, gastric mucosal dysplasia, intestinal metaplasia Raw and atrophic gastritis, chronic hepatitis and cirrhosis, colon polyps, bronchial epithelial hyperplasia and metaplasia, leukoplakia such as oral cavity, cervix and vulva, atypical hyperplasia of the endometrium, MDS and congenital diaphragmatic hernia.
- the mode of administration of the phenol glycoside derivative is not particularly limited. It can be administered orally as well as intravenously, intramuscularly, topically, intratumorally, peritumoral or subcutaneously. A preferred mode is oral, intravenous, intratumoral administration.
- the main advantage of the present invention is that the phenolic glycoside derivative of the present invention inhibits abnormal growth of cells in a broad spectrum and is targeted, and the combination of other drugs can significantly enhance the drug efficacy against cell abnormal proliferation.
- the invention is further described in the following detailed description of the embodiments of the invention. The experimental methods in which the specific conditions are not indicated in the following examples are usually carried out according to conventional conditions or according to the conditions recommended by the manufacturer.
- Example 1 Partial phenol glycoside derivatives and preparation thereof
- Phenylglycoside derivative 2 Obtained from the plant of Nandina domestica Thunb according to the method of Japanese Patent Publication P2006-176420.
- Phenolic acid derivative 3 obtained by chemical extraction from Pseudolarix kaempferi, the specific method is referred to Phytochemi stry 2006; 67: 1395-1398.
- the phenol glycoside derivative 4 was obtained from the plant of the genus Helicia Lour. by chemical extraction.
- the specific method refers to the Chinese herbal medicine, 2004, 35(5) 593-595.
- the acryloyl structure of the phenolic glycoside derivative 5 can be obtained by a conventional laboratory synthesis method as described in Bioorganic & Medicinal Chemistry Letters 16 (2006) 592-595, and then subjected to conventional chemical synthesis for glycosylation modification. Or using the microbial system to obtain S5 as described in the literature Journal of integrative Plant Biology 2007, 49(2): 207-212
- S1-S5 The structural formula of S1-S5 is as follows: (SI); (S2);
- MTT solution at a concentration of 5 mg/ml to each well, continue to culture for 4 hours, discard the culture solution, add 100 ⁇ l of dimethyl sulfoxide (MTT) per well, place for 30 minutes to dissolve the MTT crystals, and then 490nm wavelength enzyme Standard instrument detection.
- MTT dimethyl sulfoxide
- the inhibitory effect of phenolic glycoside derivative S 1-S5 on the proliferation of U87-MG cells is shown in Figure 1.
- S1-S5 has a good inhibitory effect, and S5 has the best inhibitory effect.
- Example 3 Combination of phenolic glycoside derivatives and antineoplastic agents induces mitochondrial pathway cell death.
- H1299, Du-145 and HuH-7 cells were trypsinized and then pre-cooled with ice. The cells were washed twice with PBS, and the NB4 cells were not trypsinized, and the cells were directly centrifuged, and then the cells were suspended in PBS, and finally added to a concentration of 25 g/ml PI and 5 g/ml Rhl23, and incubated at room temperature for 15 min in the dark. , flow cytometry detection.
- FIG. 2A shows S2 50 ⁇ ⁇ / ⁇ 1 concentration of doxorubicin monotherapy with human hepatoma HuH-7 induced mitochondrial membrane potential and decreased after death (ADR) g / ml concentration combination.
- 2B shows induced after S3 80 ⁇ ⁇ / ⁇ 1 concentration monotherapy with cisplatin (CDDP) 5 (g / ml combination prostate Du-145 cell mitochondrial membrane potential loss and death.
- CDDP cisplatin
- FIG. 2C shows S4 5 (g / ml Concentration of single drug and vinorelbine (VNB) combined to reduce mitochondrial membrane potential and death in human non-small cell lung cancer H1299 cells.
- Figure 2D shows S5 4 (g/ml concentration of single drug and all-trans retinoic acid (ATRA)
- ATRA all-trans retinoic acid
- PK11 195 is a known ligand for mitochondrial PBR (mPBR), and a radioligand binding assay is used to evaluate whether a phenol glycoside derivative binds to mPBR.
- Mitochondria were extracted from Wi star rat heart tissue using the mitochondrial extraction kit (Beijing Baosai Biotechnology Co., Ltd.), and the S1 compounds were 0, 0.01, 0.1, 0.5, 1, 5, and 10 ⁇ , respectively.
- ⁇ Concentration and 0. 3 nM 3 H- PK11 195 mixed in 50 mM The radiation intensity was measured after 30 min in Tri s-HCl, 10 mM MgC12, pH 7.5 solution.
- the IC50 of S1 was 152.77 nM, which was obtained by fitting the intensity of the relative combination.
- the cell concentration was 1. 5 X 10 7 /ml, and the cell concentration was 1. 5 X 10 7 /ml.
- 50 mg/kg or 100 mg/kg of S 1 solution (solvent for water) was administered orally once a week, and the CDDP solvent was intraperitoneally injected once a week.
- the CDDP group was given once a week.
- CDDP 5mg/kg (solvent is normal saline)
- the control group was intraperitoneally injected with the same volume of CDDP solvent and the same amount of S1 solvent was administered to the control group until the tumor of the control group appeared necrosis.
- the experiment results in each group of tumors. The average number of volumes is expressed.
- Fig. 4 The results are shown in Fig. 4. It can be seen that the phenolic glycoside derivative alone and in combination with cisplatin can inhibit the growth of Huh-7 human liver cancer xenografts in nude mice, and the combined application effect is more excellent.
- Example 6 The phenolic glycoside derivative alone and in combination with docetaxel (DXT) inhibits SPC-A-1 human non-small cell lung cancer xenograft tumor
- Planting xenograft tumor SPC-A-1 (purchased from the Chinese Academy of Sciences Shanghai Institute of Life Sciences cell bank) method is consistent with the method in Example 5, S2 is 50 mg/kg orally 5 times a week (solvent is water), DXT group weekly A 20 mg/kg DXT (solvent was absolute ethanol/tween-80/water) was injected intraperitoneally.
- the control group was intraperitoneally injected with the same amount of normal saline and an equal amount of S2 solvent.
- the method of implanting xenograft tumor SPC-A-1 was consistent with the method of Example 5.
- the S4 group was orally administered with a 50 mg/kg dose of S4 solution (solvent for water) five times a week, and the cisplatin group was intraperitoneally injected with 5 mg once a week. /kg cisplatin (solvent is normal saline), and the control group was orally administered with normal saline as a negative control.
- the method of implanting xenograft tumor Be l-7402 (purchased from the Chinese Academy of Sciences Shanghai Institute of Bioscience Cell Bank) is the same as that in Example 5, and the compound group is administered orally 30 mg/kg 5 times a week (solvent is water); sorafenib The group was given 5 times a week, each time with a 20 mg/kg sorafenib solution (dissolved in ethanol/water of pentahydrate), and the control group was given an equal amount of S5 solvent and sorafenib solvent.
- Bone marrow samples from patients with MDS were obtained, and MDS cells with a purity of about 90% were isolated by lymphocyte separation solution.
- the lymphocyte culture medium containing 15% fetal bovine serum was mixed to a concentration of 5 ⁇ 107 ml, and 200 ⁇ l per well was seeded in a 96-well plate.
- each compound has three parallel duplicate wells, wherein the concentration of cyclosporine A (CsA) is 2uM, the concentration of S1-S5 is 40 ⁇ ⁇ / ⁇ 1, and the concentration is 37 °C, saturated humidity, 5% C0 after dosing.
- CsA cyclosporine A
- DMBA Dimethylol butyric acid
- 50 ⁇ l per animal per day fasted for 2 hours after application
- each treatment group including S l, S2, S3, S4 and S5 groups
- S1, S2, S3, S4 or S5 lOOmg/kg body weight in drinking water during which the positive control group was consumed.
- Tap water negative control with acetone and tap water.
- the animals were sacrificed, and the oral mucosa was taken and fixed for pathological examination. The incidence of malignant transformation of oral mucosa was compared between groups.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008801277993A CN101977612A (zh) | 2008-02-28 | 2008-02-28 | 苯酚苷衍生物在制备抗细胞增生疾病组合物中的应用 |
PCT/CN2008/070373 WO2009105936A1 (zh) | 2008-02-28 | 2008-02-28 | 苯酚苷衍生物在制备抗细胞增生疾病组合物中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2008/070373 WO2009105936A1 (zh) | 2008-02-28 | 2008-02-28 | 苯酚苷衍生物在制备抗细胞增生疾病组合物中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2009105936A1 true WO2009105936A1 (zh) | 2009-09-03 |
Family
ID=41015506
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2008/070373 WO2009105936A1 (zh) | 2008-02-28 | 2008-02-28 | 苯酚苷衍生物在制备抗细胞增生疾病组合物中的应用 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN101977612A (zh) |
WO (1) | WO2009105936A1 (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130288992A1 (en) * | 2010-12-22 | 2013-10-31 | Ajinomoto Co., Inc. | Glycoside compound |
CN105367614A (zh) * | 2015-11-24 | 2016-03-02 | 中国人民解放军第二军医大学 | 含有葡萄糖类脂肪酸衍生物的制备方法及其在医药领域的应用 |
CN105859805A (zh) * | 2016-05-08 | 2016-08-17 | 黑龙江中医药大学 | 核桃青皮中一种新的酚苷化合物的制备方法和用途 |
CN111892634A (zh) * | 2020-09-29 | 2020-11-06 | 江西业力医疗器械有限公司 | 一种源于生等的糖苷化合物、提取方法及其应用 |
CN112043717A (zh) * | 2020-05-14 | 2020-12-08 | 青岛市肿瘤医院 | 一种治疗肺癌的药物组合物及其制剂 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006176420A (ja) * | 2004-12-21 | 2006-07-06 | Univ Of Tokushima | チロシナーゼ活性阻害剤、その製法及び用途 |
-
2008
- 2008-02-28 WO PCT/CN2008/070373 patent/WO2009105936A1/zh active Application Filing
- 2008-02-28 CN CN2008801277993A patent/CN101977612A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006176420A (ja) * | 2004-12-21 | 2006-07-06 | Univ Of Tokushima | チロシナーゼ活性阻害剤、その製法及び用途 |
Non-Patent Citations (5)
Title |
---|
CHUN-YANYAN ET AL.: "Biotransformation of 4-Hydroxybenzen Derivatives by Hairy Root Cultures of Polygonum multiflorum Thunb.", JOURNAL OF INTEGRATIVE PLANT BIOLOGY., vol. 49, no. 2, 2007, pages 207 - 2I2 * |
GUO ZHENGPING ET AL.: "Study of the Mechanism of Gastrodin and Derivatives of Gastrodigenin.", JOURNAL OF WEST CHINA UNIVERSITY OF MEDICAL SCIENCES (CHINESE)., vol. 22, no. 1, 1991, pages 79 - 82 * |
LI E. ET AL.: "In Vitro Research on the Effects Against Drug-Resistant Tumor Cells of Nine Active Components of Traditional Chinese Drugs.", JOURNAL OF BEIJING UNIVERSITY OFTCM (CHINESE)., vol. 27, no. 2, March 2004 (2004-03-01), pages 24 - 26 * |
PENG LIU ET AL.: "Benzoic acid allopyranosides from the bark of Pseudolarix kaempferi.", PHYTOCHEMISTRY, vol. 67, 2006, pages 1395 - 1398 * |
ZHAO JINPING ET AL.: "Study on the Chemical Constituents of Helicia Clivicola.", NATURAL PRODUC RESEARCH AND DEVELOPMENT (CHINESE)., vol. 3, no. 3, September 1991 (1991-09-01), pages 7 - 11 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130288992A1 (en) * | 2010-12-22 | 2013-10-31 | Ajinomoto Co., Inc. | Glycoside compound |
JPWO2012086812A1 (ja) * | 2010-12-22 | 2014-06-05 | 味の素株式会社 | 配糖体化合物 |
US9175028B2 (en) | 2010-12-22 | 2015-11-03 | Ajinomoto Co., Inc. | Glycoside compound |
JP5857975B2 (ja) * | 2010-12-22 | 2016-02-10 | 味の素株式会社 | 配糖体化合物 |
CN105367614A (zh) * | 2015-11-24 | 2016-03-02 | 中国人民解放军第二军医大学 | 含有葡萄糖类脂肪酸衍生物的制备方法及其在医药领域的应用 |
CN105859805A (zh) * | 2016-05-08 | 2016-08-17 | 黑龙江中医药大学 | 核桃青皮中一种新的酚苷化合物的制备方法和用途 |
CN112043717A (zh) * | 2020-05-14 | 2020-12-08 | 青岛市肿瘤医院 | 一种治疗肺癌的药物组合物及其制剂 |
CN112043717B (zh) * | 2020-05-14 | 2022-10-04 | 青岛市肿瘤医院 | 一种治疗肺癌的药物组合物及其制剂 |
CN111892634A (zh) * | 2020-09-29 | 2020-11-06 | 江西业力医疗器械有限公司 | 一种源于生等的糖苷化合物、提取方法及其应用 |
Also Published As
Publication number | Publication date |
---|---|
CN101977612A (zh) | 2011-02-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6754071B2 (ja) | メトホルミン及びジヒドロケルセチンを含む組み合わせ医薬、及びがんの治療のための使用 | |
JP6433085B2 (ja) | がんの処置に使用するための2−アセチルナフト[2,3−b]フラン−4,9−ジオン | |
CN107001406B (zh) | 用于在肿瘤的治疗中使用的11-脱氧皮质醇的17α,21-二酯 | |
JP6937237B2 (ja) | ヒト治療薬 | |
WO2009105936A1 (zh) | 苯酚苷衍生物在制备抗细胞增生疾病组合物中的应用 | |
WO2020162638A1 (ja) | 悪性腫瘍疾患の改善用組成物 | |
JP4989469B2 (ja) | マンゴスチンの単離方法とそれを含有する医薬品、及び健康食品 | |
TW201422227A (zh) | 樟芝酸衍生物與抗癌藥物組合用於治療和/或預防腫瘤 | |
JP2016535014A (ja) | がんの処置のための医薬の組合せ | |
WO2020083353A1 (zh) | 一种3-咖啡酰奎尼酸衍生物及其制备方法和用途 | |
TW201609094A (zh) | 治療癌症之新穎方法 | |
EP3532289B1 (en) | Polyoxometalate complexes and uses in managing cancer | |
JP2011512370A (ja) | ベンゾフェナントリジン構造を有する抗腫瘍薬およびそれらを含有する製剤 | |
JP2021500465A (ja) | アントシアニン−フコイダン複合体を有効成分として含有する免疫増強剤、免疫抗ガン剤及び抗ガン剤の副作用緩和剤 | |
TW201136598A (en) | Protoilludance norsesquiterpenoid esters and uses thereof | |
PL190495B1 (pl) | Związek pochodna chalkonu, kompozycja farmaceutyczna oraz zastosowanie tego związku | |
JP6615912B2 (ja) | パナキサジオール類ジンセノサイド化合物を含む抗がん補助剤 | |
US10292972B1 (en) | Pharmaceutical composition for treating cancer and a method thereof | |
US20190231793A1 (en) | Use of harringtonines in the treatment of breast cancer, in particular triple-negative breast cancer | |
KR102287236B1 (ko) | 카탈폴 유도체 화합물을 포함하는 항암 보조제 | |
US7632863B2 (en) | 3,4,5,4′-tetramethoxyl-α,β-diphenylethane-3′-O-sodium sulphate and its use | |
KR102616323B1 (ko) | 인다카테롤을 포함하는 유방암의 치료 또는 예방용 조성물 | |
CN112535689B (zh) | 路路通内酯在治疗癌症中的应用 | |
KR102203163B1 (ko) | 산꼬리풀 추출물 또는 그의 분획물을 포함하는 항암 보조제 | |
WO2014048313A1 (zh) | 茶氨酸衍生物与羧酸香豆素衍生物的缩合产物及其中间体、其制备方法和用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200880127799.3 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 08715109 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 20/01/2011) |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 08715109 Country of ref document: EP Kind code of ref document: A1 |