Details of the Drug Combination

General Information of Drug Combination (ID: DCDBQO2)

• Drug Combination Name: Raloxifene + PMID28870136-Compound-43
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Raloxifene (DMDKF3M): Small molecular drug
  PMID28870136-Compound-43 (DMWGV8N): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DU-145
  Zero Interaction Potency (ZIP) Score: 2.83
  Bliss Independence Score: 4.14
  Loewe Additivity Score: 1.3
  LHighest Single Agent (HSA) Score: 1.27

Molecular Interaction Atlas of This Drug Combination

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]

PMID28870136-Compound-43 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ecto-5'-nucleotidase (CD73)	TTK0O6Y	5NTD_HUMAN	Inhibitor	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCGAM3P	HT29	Investigative	[9]
Adult acute myeloid leukemia	DCPA2RR	HL-60(TB)	Investigative	[9]
Anaplastic large cell lymphoma	DCGGABM	SR	Investigative	[9]
Childhood T acute lymphoblastic leukemia	DC9I0W4	CCRF-CEM	Investigative	[9]
Chronic myelogenous leukemia	DC7JFKZ	K-562	Investigative	[9]
Clear cell renal cell carcinoma	DCQ7KR7	TK-10	Investigative	[9]
Glioblastoma	DCCLXZU	SNB-75	Investigative	[9]
Papillary renal cell carcinoma	DCXEKKP	ACHN	Investigative	[9]
Renal cell carcinoma	DCF0PR1	SN12C	Investigative	[9]
Breast adenocarcinoma	DCCHNZ3	MDA-MB-468	Investigative	[10]
Adenocarcinoma	DC5XXLL	HCC-2998	Investigative	[1]
Adenocarcinoma	DC8EKGD	SW-620	Investigative	[1]
Amelanotic melanoma	DC49KEI	M14	Investigative	[1]
Cutaneous melanoma	DCZ01W4	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCYQSKW	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCCBF3W	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DCG7Q5R	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCMZ0DZ	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DCRNRGI	HOP-62	Investigative	[1]
Lung adenocarcinoma	DC8JKDH	EKVX	Investigative	[1]
Malignant melanoma	DCKU4G0	UACC62	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCMFEXN	NCI-H322M	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCYMP1W	SK-OV-3	Investigative	[1]

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] 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] Ectonucleotidase inhibitors: a patent review (2011-2016).Expert Opin Ther Pat. 2017 Dec;27(12):1291-1304.
• [9] 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.
• [10] 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.