Details of the Drug Combination

General Information of Drug Combination (ID: DCCM1PW)

• Drug Combination Name: Vinflunine + Raloxifene
• Indication: Adult acute myeloid leukemia; Status: Investigative [1]
• Component Drugs:
  Vinflunine (DMTJAEP): Small molecular drug
  Raloxifene (DMDKF3M): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HL-60(TB)
  Zero Interaction Potency (ZIP) Score: 0.91
  Bliss Independence Score: 3.57
  Loewe Additivity Score: 6.93
  LHighest Single Agent (HSA) Score: 6.37

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vinflunine

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[2]

Indication(s) of Raloxifene

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Approved	[2]

Raloxifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[3]

Raloxifene Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

Raloxifene Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[6]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[7]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Clear cell renal cell carcinoma	DC91W9S	A498	Investigative	[1]
Renal cell carcinoma	DCDPAM9	UO-31	Investigative	[1]
Invasive ductal carcinoma	DC8X7ZZ	BT-549	Investigative	[8]
Adenocarcinoma	DC9WCTJ	DU-145	Investigative	[9]
Cutaneous melanoma	DCRO588	SK-MEL-5	Investigative	[9]
High grade ovarian serous adenocarcinoma	DCAFOJI	OVCAR-5	Investigative	[9]
Lung adenocarcinoma	DCL32QO	HOP-62	Investigative	[9]
Malignant melanoma	DCUMV1Q	LOX IMVI	Investigative	[9]
Melanoma	DCBY9MG	UACC-257	Investigative	[9]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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. (Target id: 620).
• [4] Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308.
• [5] The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
• [6] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [7] Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.
• [8] 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.
• [9] 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.