General Information of Drug Combination (ID: DCDMJGF)

Drug Combination Name
Vinorelbine LY335979
Indication
Disease Entry Status REF
Human papillomavirus-related cervical adenocarcinoma Investigative [1]
Component Drugs Vinorelbine   DMVXFYE LY335979   DM2KITF
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KB-ChR-8-5-11
Zero Interaction Potency (ZIP) Score: 37.577
Bliss Independence Score: 33.905
Loewe Additivity Score: 30.605
LHighest Single Agent (HSA) Score: 26.195

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Vinorelbine
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [2]
Lung cancer 2C25.0 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [2]
Solid tumour/cancer 2A00-2F9Z Approved [3]
Vinorelbine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tubulin (TUB) TTML2WA NOUNIPROTAC Inhibitor [5]
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Vinorelbine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
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Vinorelbine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [8]
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Vinorelbine Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [9]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [9]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [10]
Vitamin K-dependent protein C (PROC) OTGVH484 PROC_HUMAN Decreases Expression [11]
Keratin, type I cytoskeletal 18 (KRT18) OTVLQFIP K1C18_HUMAN Increases Expression [12]
Epithelial cell adhesion molecule (EPCAM) OTHBZK5X EPCAM_HUMAN Increases Expression [13]
Splicing factor 45 (RBM17) OT9ROJCL SPF45_HUMAN Decreases Response To Substance [14]
Equilibrative nucleoside transporter 1 (SLC29A1) OTLOOZZS S29A1_HUMAN Affects Response To Substance [15]
Nucleophosmin (NPM1) OTTBYYT0 NPM_HUMAN Decreases Response To Substance [16]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of LY335979
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Discontinued in Phase 3 [4]
LY335979 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Multidrug resistance protein 1 (ABCB1) TT3OT40 MDR1_HUMAN Modulator [17]
Multidrug resistance protein 3 (ABCB4) TTJUXV6 MDR3_HUMAN Modulator [17]
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LY335979 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [18]
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References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 Vinorelbine FDA Label
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7105).
4 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005159)
5 Vinca alkaloid and MDR1. Gan To Kagaku Ryoho. 2008 Jul;35(7):1086-9.
6 Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8.
7 Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine. Fundam Clin Pharmacol. 2005 Oct;19(5):545-53.
8 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
9 Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues. Biomed Pharmacother. 2007 Oct;61(9):596-600.
10 Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
11 Acquired protein C deficiency following cisplatinum-navelbine administration for locally advanced breast cancer. Case report. Eur J Gynaecol Oncol. 1999;20(4):323-4.
12 Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
13 Adenocarcinoma cells exposed in vitro to Navelbine or Taxol increase Ep-CAM expression through a novel mechanism. Cancer Immunol Immunother. 2003 Jul;52(7):429-37. doi: 10.1007/s00262-003-0386-7. Epub 2003 Apr 15.
14 Human splicing factor SPF45 (RBM17) confers broad multidrug resistance to anticancer drugs when overexpressed--a phenotype partially reversed by selective estrogen receptor modulators. Cancer Res. 2005 Aug 1;65(15):6593-600. doi: 10.1158/0008-5472.CAN-03-3675.
15 High expression of nucleoside transporter protein hENT1 in Reed-Sternberg cells is associated with treatment failure in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine and liposomal doxorubicin - a CALGB 59804 correlative study. Leuk Lymphoma. 2008 Jun;49(6):1202-5. doi: 10.1080/10428190802094237.
16 Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
17 A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxoru... Clin Cancer Res. 2004 May 15;10(10):3265-72.
18 Clinical disposition, metabolism and in vitro drug-drug interaction properties of omadacycline. Xenobiotica. 2017 Aug;47(8):682-696. doi: 10.1080/00498254.2016.1213465. Epub 2016 Aug 8.