Lead Optimization of Small Molecule ENL YEATS Inhibitors to Enable


Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
11 Apr 2024
Historique:
received: 10 01 2024
revised: 04 03 2024
accepted: 07 03 2024
pmc-release: 11 04 2025
medline: 17 4 2024
pubmed: 17 4 2024
entrez: 17 4 2024
Statut: epublish

Résumé

Eleven-nineteen leukemia (ENL) is an epigenetic reader protein that drives oncogenic transcriptional programs in acute myeloid leukemia (AML). AML is one of the deadliest hematopoietic malignancies, with an overall 5-year survival rate of 27%. The epigenetic reader activity of ENL is mediated by its YEATS domain that binds to acetyl and crotonyl marks on histone tails and colocalizes with promoters of actively transcribed genes that are essential for leukemia. Prior to the discovery of

Identifiants

pubmed: 38628784
doi: 10.1021/acsmedchemlett.4c00016
pmc: PMC11017412
doi:

Types de publication

Journal Article

Langues

eng

Pagination

524-532

Informations de copyright

© 2024 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare the following competing financial interest(s): T.A.K., M.M., M.W.M., Y.F., A.W.S., P.T.M., S.K., N.J.L., and D.J.H. are current or former employees of the Sanders Tri-Institutional Therapeutics Discovery Institute (TDI) and may benefit from the further development and licensure of molecules described herein.

Auteurs

Mayako Michino (M)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.

Tanweer A Khan (TA)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.

Michael W Miller (MW)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.

Yoshiyuki Fukase (Y)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.

Jeremie Vendome (J)

Schrödinger, Inc., 1540 Broadway, 24th Floor, New York, New York 10036, United States.

Carolina Adura (C)

Fisher Drug Discovery Resource Center, The Rockefeller University, New York, New York 10065, United States.

J Fraser Glickman (JF)

Fisher Drug Discovery Resource Center, The Rockefeller University, New York, New York 10065, United States.

Yiman Liu (Y)

Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States.

Liling Wan (L)

Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States.

C David Allis (CD)

Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065, United States.

Andrew W Stamford (AW)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.

Peter T Meinke (PT)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.
Department of Pharmacology, Weill Cornell Medicine, New York, New York 10021, United States.

Louis M Renzetti (LM)

Bridge Medicines, The Rockefeller University, 1230 York Avenue, Smith Hall Annex, C-Floor, New York, New York 10065, United States.

Stacia Kargman (S)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.
Bridge Medicines, The Rockefeller University, 1230 York Avenue, Smith Hall Annex, C-Floor, New York, New York 10065, United States.

Nigel J Liverton (NJ)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.

David J Huggins (DJ)

Sanders Tri-Institutional Therapeutics Discovery Institute, 1230 York Ave, Box 122, New York, New York 10065, United States.
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York 10021, United States.

Classifications MeSH