Details of the Drug Combination

General Information of Drug Combination (ID: DCI9UNE)

Drug Combination Name

Cilastatin Hyodeoxycholic acid

Indication

Disease Entry	Status	REF
Chronic myelogenous leukemia	Investigative	[1]

Component Drugs

Cilastatin DME2H5T

Hyodeoxycholic acid DMSIWD0

Small molecular drug

N.A.

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: KBM-7

Zero Interaction Potency (ZIP) Score: 10.75

Bliss Independence Score: 10.75

Loewe Additivity Score: 14.28

LHighest Single Agent (HSA) Score: 14.28

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Cilastatin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Endometritis	N.A.	Approved	[2]
Peritonitis	N.A.	Approved	[2]
Pelvic inflammatory disease	GA05	Investigative	[2]

Cilastatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dehydropeptidase I (DPEP1)	TTYUENF	DPEP1_HUMAN	Inhibitor	[4]
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Cilastatin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dipeptidase 1 (DPEP1)	OTVR8V1L	DPEP1_HUMAN	Decreases Activity	[5]
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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	[8]
UDP-glucuronosyltransferase 2A3 (UGT2A3)	DEWBT6H	UD2A3_HUMAN	Metabolism	[9]
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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	Cilastatin FDA Label
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. (Ligand id: 5166).
4	Pharmacokinetic study of pleural fluid penetration of carbapenem antibiotic agents in chemical pleurisy. Respir Med. 2006 Feb;100(2):324-31.
5	Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
6	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.
7	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.
8	Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab Rev. 1999 Nov;31(4):817-99.
9	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.