General Information of Drug Combination (ID: DCCX72M)

Drug Combination Name
Vinorelbine SNX-2112
Indication
Disease Entry Status REF
Malignant melanoma Investigative [1]
Component Drugs Vinorelbine   DMVXFYE SNX-2112   DMB5A80
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: RPMI7951
Zero Interaction Potency (ZIP) Score: 4.56
Bliss Independence Score: 4.27
Loewe Additivity Score: 3.58
LHighest Single Agent (HSA) Score: 6.71

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 SNX-2112
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
SNX-2112 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Heat shock protein 90 alpha (HSP90A) TT78R5H HS90A_HUMAN Inhibitor [4]
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SNX-2112 Interacts with 14 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK) OTLF4ZB1 IKKA_HUMAN Decreases Expression [17]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [17]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [17]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Decreases Expression [17]
Endoplasmin (HSP90B1) OT02XLBR ENPL_HUMAN Decreases Expression [17]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [17]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [17]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Expression [17]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [17]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Expression [17]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [17]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [17]
Heat shock protein 75 kDa, mitochondrial (TRAP1) OTNG0L8J TRAP1_HUMAN Decreases Expression [17]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [17]
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⏷ Show the Full List of 14 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DCM1923 UWB1289+BRCA1 Investigative [18]
Breast carcinoma DCRMX0G OCUBM Investigative [18]
Carcinoma DC6RE84 OV90 Investigative [18]
Carcinoma DCJ9F7D MDAMB436 Investigative [18]
Colon carcinoma DCNDT9Q RKO Investigative [18]
Invasive ductal carcinoma DC63M2O T-47D Investigative [18]
Rectal adenocarcinoma DCMTRAE SW837 Investigative [18]
Adenocarcinoma DCHMH73 CAOV3 Investigative [1]
Adenocarcinoma DC7DKNL NCIH1650 Investigative [1]
Adenocarcinoma DCXX754 COLO320DM Investigative [1]
Adenocarcinoma DCARXYR HCT116 Investigative [1]
Amelanotic melanoma DCY7GMF A2058 Investigative [1]
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCR8TU2 ES2 Investigative [1]
Germ cell tumour DCDBH1P PA1 Investigative [1]
Large cell lung carcinoma DCCXUQ9 NCI-H460 Investigative [1]
Malignant melanoma DC6RETK A375 Investigative [1]
Malignant melanoma DCVWSBF HT144 Investigative [1]
Mesothelioma DCL8JPD MSTO Investigative [1]
Non small cell carcinoma DCA3GJX SKMES1 Investigative [1]
Ovarian endometrioid adenocarcinoma DCD0RIL A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DCTABWZ SK-OV-3 Investigative [1]
Prostate carcinoma DCDOV5M LNCAP Investigative [1]
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⏷ Show the Full List of 22 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 Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
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 The Hsp90 inhibitor SNX-2112, induces apoptosis in multidrug resistant K562/ADR cells through suppression of Akt/NF-B and disruption of mitochondria-dependent pathways. Chem Biol Interact. 2013 Sep 5;205(1):1-10. doi: 10.1016/j.cbi.2013.06.007. Epub 2013 Jun 15.
18 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.