Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMOB58Q)

• Drug Name: MK-8228 Drug Info
• Synonyms: Letermovir

Indication

Disease Entry	ICD 11	Status	REF
Cytomegalovirus Disease	1D82	Approved	[1]
Cytomegalovirus infection	1D82	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 45138674
  CAS Number: CAS 917389-32-3
  TTD Drug ID: DMOB58Q
  VARIDT Drug ID: DR00621
  INTEDE Drug ID: DR0928
  ACDINA Drug ID: D00355

Molecule-Related Drug Atlas

Drug(s) Targeting Cytomegalovirus Terminase (CMV TRM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GW-275175	DMGSN1V	Virus infection	1A24-1D9Z	Terminated	[4]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[5]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[6]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[7]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[8]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[9]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[10]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[11]
Metronidazole	DMTIVEN	Abscess		Approved	[12]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[13]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[14]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cytomegalovirus Terminase (CMV TRM)	TTZHSBO	NOUNIPROTAC	Inhibitor	[1]
Cytomegalovirus Terminase UL56 (CMV TRM1)	TTOGPL1	TRM1_HCMVA	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME	DEYGVN4	UD11_HUMAN	Substrate	[3]

References

• [1] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [2] The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011 Oct;85(20):10884-93.
• [3] Pharmacogenetic analysis of OATP1B1, UGT1A1, and BCRP variants in relation to the pharmacokinetics of letermovir in previously conducted clinical studies. J Clin Pharmacol. 2019 Sep;59(9):1236-1243.
• [4] Progress in Drug Research, 2012. Page(106).
• [5] Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
• [6] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
• [7] Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
• [8] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
• [9] Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
• [10] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
• [11] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [12] 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.
• [13] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [14] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.