Details of the Drug Combination

General Information of Drug Combination (ID: DCY5EOI)

Drug Combination Name
Repaglinide Hyodeoxycholic acid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Repaglinide   DM5SXUV Hyodeoxycholic acid   DMSIWD0
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 11.52
Bliss Independence Score: 11.52
Loewe Additivity Score: 14.98
LHighest Single Agent (HSA) Score: 15.03

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Repaglinide
Disease Entry ICD 11 Status REF
Diabetic complication 5A2Y Approved [2]
Repaglinide Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ATP-binding cassette transporter C9 (ABCC9) TTEF5MJ ABCC9_HUMAN Blocker [3]
ATP-binding cassette transporter C8 (ABCC8) TTP835K ABCC8_HUMAN Blocker [3]
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Repaglinide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [4]
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Repaglinide 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]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [5]
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Repaglinide Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Affects Metabolism [7]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [8]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [9]
HLA class I histocompatibility antigen, alpha chain F (HLA-F) OT76CM19 HLAF_HUMAN Affects Expression [10]
Solute carrier family 15 member 1 (SLC15A1) OT1P16B5 S15A1_HUMAN Decreases Activity [11]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [10]
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⏷ Show the Full List of 6 DOT(s)
Hyodeoxycholic acid Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A6 (UGT1A6) DESD26P UD16_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 2A3 (UGT2A3) DEWBT6H UD2A3_HUMAN Metabolism [15]
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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 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: 6841).
3 Metformin/Repaglinide (PrandiMet) for type 2 diabetes. Med Lett Drugs Ther. 2009 Jun 1;51(1313):41-3.
4 Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium. Clin Pharmacol Ther. 2018 Nov;104(5):900-915.
5 Drug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide. Clin Pharmacokinet. 2007;46(2):93-108.
6 Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism. Br J Clin Pharmacol. 2010 Dec;70(6):870-80.
7 Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther. 2005 Jun;77(6):468-78. doi: 10.1016/j.clpt.2005.01.018.
8 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
9 Toxicological evaluation of acyl glucuronides utilizing half-lives, peptide adducts, and immunostimulation assays. Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):241-9.
10 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
11 In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors. Pharm Res. 2005 Apr;22(4):512-7. doi: 10.1007/s11095-005-2505-y. Epub 2005 Apr 7.
12 Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
13 Isolation and characterization of hyodeoxycholic-acid: UDP-glucuronosyltransferase from human liver. Eur J Biochem. 1991 Sep 1;200(2):393-400. doi: 10.1111/j.1432-1033.1991.tb16197.x.
14 Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab Rev. 1999 Nov;31(4):817-99.
15 Novel polymorphic human UDP-glucuronosyltransferase 2A3: cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction. Mol Pharmacol. 2008 Sep;74(3):744-54.