Details of the Drug Combination

General Information of Drug Combination (ID: DC65TFK)

• Drug Combination Name: Vinorelbine + RTB101
• Indication: Breast carcinoma; Status: Investigative [1]
• Component Drugs:
  Vinorelbine (DMVXFYE): Small molecular drug
  RTB101 (DM62QTW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: ZR751
  Zero Interaction Potency (ZIP) Score: 2.53
  Bliss Independence Score: 1.12
  Loewe Additivity Score: 9.42
  LHighest Single Agent (HSA) Score: 11.07

Molecular Interaction Atlas of This Drug Combination

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]

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]

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]

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]

Indication(s) of RTB101

Disease Entry	ICD 11	Status	REF
Respiratory tract infection	CA45	Phase 3	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]

RTB101 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
CREB-regulated transcription coactivator 1 (TORC1)	TT4GO0F	CRTC1_HUMAN	Inhibitor	[18]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DCF0T30	UWB1289	Investigative	[1]
Breast and ovarian cancer syndrome	DC7UU2U	UWB1289+BRCA1	Investigative	[1]
Breast carcinoma	DCFHG4M	KPL1	Investigative	[1]
Breast carcinoma	DCYLZLX	OCUBM	Investigative	[1]
Carcinoma	DCL8TSS	OV90	Investigative	[1]
Carcinoma	DC113KU	EFM192B	Investigative	[1]
Carcinoma	DCIT7OA	MDAMB436	Investigative	[1]
Colon carcinoma	DCI9FN5	RKO	Investigative	[1]
Invasive ductal carcinoma	DCSEJ9R	T-47D	Investigative	[1]
Rectal adenocarcinoma	DCYISEV	SW837	Investigative	[1]
Adenocarcinoma	DCZEDNJ	OVCAR3	Investigative	[19]
Adenocarcinoma	DCXYZPH	NCIH2122	Investigative	[19]
Adenocarcinoma	DCCBYMY	NCIH520	Investigative	[19]
Adenocarcinoma	DCXON7B	COLO320DM	Investigative	[19]
Adenocarcinoma	DC24MQE	DLD1	Investigative	[19]
Adenocarcinoma	DC7SC5X	HCT116	Investigative	[19]
Adenocarcinoma	DCXG6YT	HT29	Investigative	[19]
Adenocarcinoma	DCH8HUZ	SW-620	Investigative	[19]
Amelanotic melanoma	DCEKEVB	A2058	Investigative	[19]
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DC5HM33	ES2	Investigative	[19]
Germ cell tumour	DCAX45X	PA1	Investigative	[19]
Large cell lung carcinoma	DCB8YDX	NCI-H460	Investigative	[19]
Malignant melanoma	DC4YWJ8	A375	Investigative	[19]
Malignant melanoma	DCNUY14	HT144	Investigative	[19]
Malignant melanoma	DC90Q7F	RPMI7951	Investigative	[19]
Malignant melanoma	DCWW5WO	SKMEL30	Investigative	[19]
Malignant melanoma	DCZ9ZAQ	UACC62	Investigative	[19]
Mesothelioma	DCPHLQ0	MSTO	Investigative	[19]
Non small cell carcinoma	DCX16J7	SKMES1	Investigative	[19]
Ovarian endometrioid adenocarcinoma	DCL3MY4	A2780	Investigative	[19]
Ovarian serous cystadenocarcinoma	DC9WI8S	SK-OV-3	Investigative	[19]
Prostate carcinoma	DCFAH69	LNCAP	Investigative	[19]

References

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• [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 (NCT04139915) Effect of RTB101 on Illness Associated With Respiratory Tract Infections in the Elderly. U.S. National Institutes of Health.
• [5] ClinicalTrials.gov (NCT04409327) Phase 2 Study to Determine if RTB101 Reduces the Severity of COVID-19 in Older Adults Residing in Nursing Homes. U.S. National Institutes of Health.
• [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.
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• [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] Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.
• [19] 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.