General Information of Drug Combination (ID: DCDMU19)

Drug Combination Name
Vinorelbine MK-4827
Indication
Disease Entry Status REF
Ovarian serous cystadenocarcinoma Investigative [1]
Component Drugs Vinorelbine   DMVXFYE MK-4827   DMLYGH4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SK-OV-3
Zero Interaction Potency (ZIP) Score: 7.41
Bliss Independence Score: 7.14
Loewe Additivity Score: 10.72
LHighest Single Agent (HSA) Score: 13.25

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 [6]
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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 [7]
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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 [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [9]
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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 [10]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [10]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [11]
Vitamin K-dependent protein C (PROC) OTGVH484 PROC_HUMAN Decreases Expression [12]
Keratin, type I cytoskeletal 18 (KRT18) OTVLQFIP K1C18_HUMAN Increases Expression [13]
Epithelial cell adhesion molecule (EPCAM) OTHBZK5X EPCAM_HUMAN Increases Expression [14]
Splicing factor 45 (RBM17) OT9ROJCL SPF45_HUMAN Decreases Response To Substance [15]
Equilibrative nucleoside transporter 1 (SLC29A1) OTLOOZZS S29A1_HUMAN Affects Response To Substance [16]
Nucleophosmin (NPM1) OTTBYYT0 NPM_HUMAN Decreases Response To Substance [17]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [4]
Breast cancer 2C60-2C65 Phase 2 [5]
Ewing sarcoma 2B52 Phase 1 [5]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [18]
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MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [19]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [20]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [20]
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MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [21]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DCSVNM0 UWB1289 Investigative [22]
Breast and ovarian cancer syndrome DC1C3VF UWB1289+BRCA1 Investigative [22]
Breast carcinoma DCQ6LSR KPL1 Investigative [22]
Breast carcinoma DCERZHW OCUBM Investigative [22]
Carcinoma DCHZQGL OV90 Investigative [22]
Carcinoma DCSMI3Q EFM192B Investigative [22]
Colon adenocarcinoma DC04C30 LOVO Investigative [22]
Colon carcinoma DCVOPC2 RKO Investigative [22]
Invasive ductal carcinoma DCMVKO8 T-47D Investigative [22]
Rectal adenocarcinoma DCFU6XM SW837 Investigative [22]
Adenocarcinoma DCS41WW NCIH1650 Investigative [1]
Adenocarcinoma DCR2ZR4 NCIH520 Investigative [1]
Adenocarcinoma DCIBRTN COLO320DM Investigative [1]
Adenocarcinoma DCV6A07 DLD1 Investigative [1]
Adenocarcinoma DCHGUSB HT29 Investigative [1]
Adenocarcinoma DCGOMQV SW-620 Investigative [1]
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCHOXZ7 ES2 Investigative [1]
Large cell lung carcinoma DCU4KVY NCI-H460 Investigative [1]
Malignant melanoma DCZE4K9 RPMI7951 Investigative [1]
Malignant melanoma DCU28TH SKMEL30 Investigative [1]
Mesothelioma DCB5IEW MSTO Investigative [1]
Non small cell carcinoma DCYKNJH SKMES1 Investigative [1]
Ovarian endometrioid adenocarcinoma DCVBP23 A2780 Investigative [1]
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⏷ Show the Full List of 23 DrugCom(s)

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 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Vinca alkaloid and MDR1. Gan To Kagaku Ryoho. 2008 Jul;35(7):1086-9.
7 Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8.
8 Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine. Fundam Clin Pharmacol. 2005 Oct;19(5):545-53.
9 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
10 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.
11 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.
12 Acquired protein C deficiency following cisplatinum-navelbine administration for locally advanced breast cancer. Case report. Eur J Gynaecol Oncol. 1999;20(4):323-4.
13 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.
14 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.
15 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.
16 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.
17 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.
18 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
19 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
20 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
21 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
22 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.