Issue 5, 2013
From the journal:

MedChemComm

Synthesis, activity and metabolic stability of non-ribose containing inhibitors of histone methyltransferase DOT1L†

Lisheng Deng,‡a   Li Zhang,‡a   Yuan Yao,a   Cong Wang,a   Michele S. Redell,b   Shuo Dongc  and  Yongcheng Song*a  

* Corresponding authors

a Department of Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA
E-mail: ysong@bcm.edu
Fax: +1 713-798-3145
Tel: +1 713-798-7415

b Department of Pediatrics, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA

c Department of Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA

Abstract

Histone methyltransferase DOT1L is a drug target for MLL leukemia. We report an efficient synthesis of a cyclopentane-containing compound that potently and selectively inhibits DOT1L (Ki = 1.1 nM) as well as H3K79 methylation (IC50 ∼ 200 nM). Importantly, this compound exhibits a high stability in plasma and liver microsomes, suggesting it is a better drug candidate.

Graphical abstract: Synthesis, activity and metabolic stability of non-ribose containing inhibitors of histone methyltransferase DOT1L

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Article information

DOI
https://doi.org/10.1039/C3MD00021D
Article type
Concise Article
Submitted
16 Jan 2013
Accepted
12 Mar 2013
First published
12 Mar 2013

Med. Chem. Commun., 2013,4, 822-826

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Synthesis, activity and metabolic stability of non-ribose containing inhibitors of histone methyltransferase DOT1L

L. Deng, L. Zhang, Y. Yao, C. Wang, M. S. Redell, S. Dong and Y. Song, Med. Chem. Commun., 2013, 4, 822 DOI: 10.1039/C3MD00021D

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