Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 13, Issue 9, Pages 1379-1383Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.2c00319
Keywords
mRNA display; peptide therapeutics; macrocyclic peptides; noncanonical amino acids; proprotein convertase subtilisin; kexin type 9; hypercholesterolemia
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Funding
- NIGMS [NIH 1R35GM125005]
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In this article, we discuss the successful development of an mRNA display-derived clinical candidate by Merck & Co., which is a bioavailable inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). The challenges in the chemical and pharmacological aspects of bringing this compound to trials are highlighted, and the current outlook for mRNA display-based therapeutic development is examined.
Merck & Co. recently reported one of the first mRNA display-derived clinical candidates in a bioavailable inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). Herein, we discuss the chemical and pharmacological challenges surmounted in bringing this compound to trials and the current outlook for mRNA display-based therapeutic development.
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