Details of the Drug Combination

General Information of Drug Combination (ID: DCJXGER)

Drug Combination Name
FORMESTANE Raloxifene
Indication
Disease Entry Status REF
High grade ovarian serous adenocarcinoma Investigative [1]
Component Drugs FORMESTANE   DMWIDJK Raloxifene   DMDKF3M
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: OVCAR-8
Zero Interaction Potency (ZIP) Score: 1.23
Bliss Independence Score: 2.91
Loewe Additivity Score: 2.39
LHighest Single Agent (HSA) Score: 0.53

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of FORMESTANE
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Withdrawn from market [2]
FORMESTANE Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [3]
------------------------------------------------------------------------------------
FORMESTANE Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [4]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [5]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) OT6EBDHM DHB1_HUMAN Decreases Activity [6]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Increases Expression [7]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Expression [7]
------------------------------------------------------------------------------------
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 [8]
------------------------------------------------------------------------------------
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 [9]
------------------------------------------------------------------------------------
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 [10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DEL5N6Y UD110_HUMAN Metabolism [12]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DC69LGE MOLT-4 Investigative [1]
Anaplastic large cell lymphoma DCBSMMK SR Investigative [1]
Astrocytoma DCXZIOD SNB-19 Investigative [1]
Glioma DCCE723 SF-539 Investigative [1]
------------------------------------------------------------------------------------

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 The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
4 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
5 Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro. 2000 Jun;14(3):227-34.
6 Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. J Steroid Biochem Mol Biol. 2005 Apr;94(5):461-7.
7 Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays. Toxicol Lett. 2018 Aug;292:39-45. doi: 10.1016/j.toxlet.2018.04.026. Epub 2018 Apr 24.
8 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).
9 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.
10 The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
11 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.
12 Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.