title: Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1).
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.
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Brendan
authors.initials: B
authors.lastname: D'Souza
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Thompson
authors.affiliation: Beryllium , 3 Preston Court, Bedford, Massachusetts 01730, United States.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Clifton
authors.affiliation: Beryllium , 3 Preston Court, Bedford, Massachusetts 01730, United States.
authors.forename: James W
authors.initials: JW
authors.lastname: Fairman
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Ben
authors.initials: B
authors.lastname: Fulroth
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Alison
authors.initials: A
authors.lastname: Leed
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: McCarren
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Clementine
authors.initials: C
authors.lastname: Feau
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Virendar K
authors.initials: VK
authors.lastname: Kaushik
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Palmer
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States ; Dana-Farber Cancer Institute and Howard Hughes Medical Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, United States.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Hubbard
authors.affiliation: Broad Institute , 415 Main Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Serrano-Wu
keywords: MCL1; biophysical validation; myeloid cell leukemia 1; sp3-rich