Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1).

ACS Med Chem Lett
Authors
Abstract

A direct binding screen of 100 000 sp(3)-rich molecules identified a single diastereomer of a macrolactam core that binds specifically to myeloid cell leukemia 1 (MCL1). A comprehensive toolbox of biophysical methods was applied to validate the original hit and subsequent analogues and also established a binding mode competitive with NOXA BH3 peptide. X-ray crystallography of ligand bound to MCL1 reveals a remarkable ligand/protein shape complementarity that diverges from previously disclosed MCL1 inhibitor costructures.

Year of Publication
2014
Journal
ACS Med Chem Lett
Volume
5
Issue
12
Pages
1308-12
Date Published
2014 Dec 11
ISSN
1948-5875
URL
DOI
10.1021/ml500388q
PubMed ID
25516789
PubMed Central ID
PMC4265822
Links