Details of the Drug Combination

General Information of Drug Combination (ID: DCKNT1B)

• Drug Combination Name: ABIRATERONE + Raloxifene
• Indication: Glioblastoma; Status: Investigative [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  Raloxifene (DMDKF3M): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SNB-75
  Zero Interaction Potency (ZIP) Score: 0.83
  Bliss Independence Score: 3.94
  Loewe Additivity Score: 3.27
  LHighest Single Agent (HSA) Score: 3.45

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ABIRATERONE

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[2]

ABIRATERONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-monooxygenase (S17AH)	TTRA5BZ	CP17A_HUMAN	Modulator	[4]

Indication(s) of Raloxifene

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Approved	[3]

Raloxifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[5]

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	[6]

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	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCSACHY	HL-60(TB)	Investigative	[1]
Astrocytoma	DCTM6FL	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCXQMD7	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCQ14AB	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCMR12C	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCV3SQE	TK-10	Investigative	[1]
Glioma	DCR5M3A	SF-268	Investigative	[1]
Carcinoma	DCELGUC	MCF7	Investigative	[10]
Colon adenocarcinoma	DC8S136	COLO 205	Investigative	[10]
Invasive ductal carcinoma	DCK4XNC	BT-549	Investigative	[10]
Invasive ductal carcinoma	DC03WRB	T-47D	Investigative	[10]
Invasive ductal carcinoma	DCP5HZ3	HS 578T	Investigative	[10]
Adenocarcinoma	DCLHYLO	DU-145	Investigative	[11]
Adenocarcinoma	DCJC9CL	NCIH23	Investigative	[11]
Adenocarcinoma	DCCLFLB	HT29	Investigative	[11]
Adenocarcinoma	DC8A96I	HCT116	Investigative	[11]
Amelanotic melanoma	DC58G3J	MDA-MB-435	Investigative	[11]
Amelanotic melanoma	DCNG3B5	M14	Investigative	[11]
Cutaneous melanoma	DCKWIP2	SK-MEL-28	Investigative	[11]
High grade ovarian serous adenocarcinoma	DCAPMSM	OVCAR-8	Investigative	[11]
High grade ovarian serous adenocarcinoma	DCLXAAQ	OVCAR-5	Investigative	[11]
Large cell lung carcinoma	DC7OCPC	NCI-H460	Investigative	[11]
Lung adenocarcinoma	DCML8JI	HOP-62	Investigative	[11]
Lung adenocarcinoma	DCXDUSI	EKVX	Investigative	[11]
Lung adenocarcinoma	DCNCBQ9	NCI-H522	Investigative	[11]
Melanoma	DCMN4MU	SK-MEL-2	Investigative	[11]
Melanoma	DCYL1PB	MALME-3M	Investigative	[11]
Minimally invasive lung adenocarcinoma	DCY2CUS	NCI-H322M	Investigative	[11]
Non-small cell lung carcinoma	DC8IZGS	HOP-92	Investigative	[11]
Ovarian serous cystadenocarcinoma	DCBT4M9	SK-OV-3	Investigative	[11]
Pleural epithelioid mesothelioma	DCFY0Q5	NCI-H226	Investigative	[11]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] 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: 6745).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [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. (Target id: 620).
• [6] 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.
• [7] The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
• [8] 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.
• [9] Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.
• [10] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
• [11] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976