Details of the Drug Combination

General Information of Drug Combination (ID: DC8BII9)

Drug Combination Name
LIAROZOLE Raloxifene
Indication
Disease Entry Status REF
Melanoma Investigative [1]
Component Drugs LIAROZOLE   DM4OYXE Raloxifene   DMDKF3M
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: UACC-257
Zero Interaction Potency (ZIP) Score: 0.95
Bliss Independence Score: 2.81
Loewe Additivity Score: 1.36
LHighest Single Agent (HSA) Score: 0.14

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of LIAROZOLE
Disease Entry ICD 11 Status REF
Dermatological disease DA24.Y Phase 2/3 [2]
LIAROZOLE Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [4]
Cytochrome P450 26 (CYP26A1) TTD7Q0R CP26A_HUMAN Inhibitor [5]
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LIAROZOLE Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 26A1 (CYP26A1) OTL1DFWV CP26A_HUMAN Decreases Activity [6]
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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 [7]
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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 [8]
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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 [9]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [10]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DEL5N6Y UD110_HUMAN Metabolism [11]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCGTIC1 MOLT-4 Investigative [12]
Childhood T acute lymphoblastic leukemia DCZRKZO CCRF-CEM Investigative [12]
Amelanotic melanoma DCF9TTC M14 Investigative [1]
High grade ovarian serous adenocarcinoma DC7YFSC OVCAR-5 Investigative [1]
Malignant melanoma DCAA9PP UACC62 Investigative [1]
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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 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: 5210).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
5 Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg Med Chem. 2008 Sep 1;16(17):8301-13.
6 Discovery of inhibitors of MCF-7 tumor cell adhesion to endothelial cells and investigation on their mode of action. Arch Pharm (Weinheim). 2004 Dec;337(12):687-94. doi: 10.1002/ardp.200400622.
7 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).
8 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.
9 The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
10 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.
11 Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.
12 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.