Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors.

Basic Information

ID: ALA4699549

Journal: Bioorg Med Chem Lett

Title: Synthesis and structure-activity relationship studies of LLY-507 analogues as SMYD2 inhibitors.

Authors: Zhang B,Liao L,Wu F,Zhang F,Sun Z,Chen H,Luo C

Abstract: SET and MYND domain-containing protein 2 (SMYD2), a lysine methyltransferase, is reported to catalyze the methylation of lysine residues on histone and non-histone proteins. As a potential target for cancer therapy, there are several SMYD2 inhibitors are reported, LLY-507 as a cell-active inhibitor exhibits submicromolar potency against SMYD2 in several cancer cell lines. To know which structural fragment of LLY-507 is suitable for chemical modification, three sites are chosen for structure-activity relationship studies (SARs). Among our focused library, compounds 43 and 44 with amide link on site C showed reasonably improved potency indicating that modification on this fragment is more flexible and introduction of electrophilic warheads in this position might provide lysine-targeting covalent inhibitors for SMYD2.

CiteXplore: 33011288

DOI: 10.1016/j.bmcl.2020.127598

Patent ID: ┄