Letermovir

• CAT Number: I005468
• CAS Number: 917389-32-3
• Molecular Formula: C29H28F4N4O4
• Molecular Weight: 572.6
• Purity: 98%
• Synonyms: 2-[(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4H-quinazolin-4-yl]acetic acid
• Target: CMV
• Solubility: 10 mM in DMSO
• Appearance: Solid Powder
• Storage: Store at -20°C
• Analysis method: HPLC
• IC50: 5.1±1.2 nM (EC50, HCMV-AD169 strain, CPE reduction assay)
• InChIKey: FWYSMLBETOMXAG-QHCPKHFHSA-N

Letermovir is a small molecule inhibitor of human cytomegalovirus viral replication (EC50 = ~5 nM with a selectivity index >15,000) that targets viral DNA cleavage and packaging. Letermovir functions to prevent viral DNA concatemers from forming the proper unit length and interferes with virion maturation.

Reference

1: Erb-Zohar K, Kropeit D, Scheuenpflug J, Stobernack HP, Hulskotte E, van Schanke A, Zimmermann H, Rübsamen-Schaeff H. Intravenous Hydroxypropyl β-Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single-Ascending, and Multiple-Dose Trial. Clin Transl Sci. 2017 Nov;10(6):487-495. doi: 10.1111/cts.12483. Epub 2017 Jul 4. PubMed PMID: 28675594.
2: Bowman LJ, Melaragno JI, Brennan DC. Letermovir for the management of cytomegalovirus infection. Expert Opin Investig Drugs. 2017 Feb;26(2):235-241. doi: 10.1080/13543784.2017.1274733. Epub 2016 Dec 28. Review. PubMed PMID: 27998189.
3: Wildum S, Zimmermann H, Lischka P. In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication. Antimicrob Agents Chemother. 2015;59(6):3140-8. doi: 10.1128/AAC.00114-15. Epub 2015 Mar 16. PubMed PMID: 25779572; PubMed Central PMCID: PMC4432118.
4: Goldner T, Hempel C, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother. 2014;58(1):610-3. doi: 10.1128/AAC.01794-13. Epub 2013 Nov 4. PubMed PMID: 24189264; PubMed Central PMCID: PMC3910730.
5: Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. 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. doi: 10.1128/JVI.05265-11. Epub 2011 Jul 13. PubMed PMID: 21752907; PubMed Central PMCID: PMC3187482.