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ACS Med Chem Lett DOI:10.1021/ml500388q

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

Publication TypeJournal Article
Year of Publication2014
AuthorsFang, C, D'Souza, B, Thompson, CF, Clifton, MC, Fairman, JW, Fulroth, B, Leed, A, McCarren, P, Wang, L, Wang, Y, Feau, C, Kaushik, VK, Palmer, M, Wei, G, Golub, TR, Hubbard, BK, Serrano-Wu, MH
JournalACS Med Chem Lett
Volume5
Issue12
Pages1308-12
Date Published2014 Dec 11
ISSN1948-5875
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.

URLhttp://dx.doi.org/10.1021/ml500388q
DOI10.1021/ml500388q
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25516789?dopt=Abstract

Alternate JournalACS Med Chem Lett
PubMed ID25516789
PubMed Central IDPMC4265822