Details of the Drug Combination

General Information of Drug Combination (ID: DCWJCLB)

Drug Combination Name

Carboplatin Vinorelbine

Indication

Disease Entry	Status	REF
NSCLC	Phase 3	[1]

Component Drugs

Carboplatin DMG281S

Vinorelbine DMVXFYE

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Carboplatin

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[2]
Carcinoma	2A00-2F9Z	Approved	[2]
Cholangiocarcinoma	2C12.10	Approved	[2]
Cutaneous melanoma	2C30	Approved	[2]
Epithelial ovarian cancer	2B5D	Approved	[2]
Fallopian tube neoplasm	N.A.	Approved	[2]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[2]
Lung adenocarcinoma	N.A.	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[2]
Ovarian cancer	2C73	Approved	[3]
Ovarian disorder	N.A.	Approved	[2]
Ovarian neoplasm	N.A.	Approved	[2]
Ovarian serous cystadenocarcinoma	N.A.	Approved	[2]
Small-cell lung cancer	2C25.Y	Approved	[2]
Lung large cell carcinoma	N.A.	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]

Carboplatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[6]
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Carboplatin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
High affinity copper uptake protein 1 (SLC31A1)	DTP8L4F	COPT1_HUMAN	Substrate	[7]
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Carboplatin Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[8]
Glutathione S-transferase theta-1 (GSTT1)	DE3PKUG	GSTT1_HUMAN	Metabolism	[8]
Metallothionein-1A (MT1A)	DE5ME8A	MT1A_HUMAN	Metabolism	[8]
Metallothionein-2A (MT2A)	DEFKGT7	MT2_HUMAN	Metabolism	[8]
Myeloperoxidase (MPO)	DEA3U9Y	PERM_HUMAN	Metabolism	[8]
Quinone reductase 1 (NQO1)	DENP5RY	NQO1_HUMAN	Metabolism	[8]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[8]
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⏷ Show the Full List of 7 DME(s)

Indication(s) of Vinorelbine

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Solid tumour/cancer	2A00-2F9Z	Approved	[5]

Vinorelbine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[9]
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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	[10]
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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	[11]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[12]
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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	[13]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[13]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[14]
Vitamin K-dependent protein C (PROC)	OTGVH484	PROC_HUMAN	Decreases Expression	[15]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[16]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Increases Expression	[17]
Splicing factor 45 (RBM17)	OT9ROJCL	SPF45_HUMAN	Decreases Response To Substance	[18]
Equilibrative nucleoside transporter 1 (SLC29A1)	OTLOOZZS	S29A1_HUMAN	Affects Response To Substance	[19]
Nucleophosmin (NPM1)	OTTBYYT0	NPM_HUMAN	Decreases Response To Substance	[20]
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⏷ Show the Full List of 9 DOT(s)

References

1	ClinicalTrials.gov (NCT03656393) To Evaluate the Efficacy and Safety of Gefitinib in Adjuvant Chemotherapy for Lung Adenocarcinoma
2	Carboplatin 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: 7624).
4	Vinorelbine FDA Label
5	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).
6	Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
7	Overcoming platinum drug resistance with copper-lowering agents. Anticancer Res. 2013 Oct;33(10):4157-61.
8	PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
9	Vinca alkaloid and MDR1. Gan To Kagaku Ryoho. 2008 Jul;35(7):1086-9.
10	Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8.
11	Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine. Fundam Clin Pharmacol. 2005 Oct;19(5):545-53.
12	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
13	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.
14	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.
15	Acquired protein C deficiency following cisplatinum-navelbine administration for locally advanced breast cancer. Case report. Eur J Gynaecol Oncol. 1999;20(4):323-4.
16	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.
17	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.
18	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.
19	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.
20	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.