Literature DB >> 23795283

Synthesis, Activity and Metabolic Stability of Non-Ribose Containing Inhibitors of Histone Methyltransferase DOT1L.

Lisheng Deng1, Li Zhang, Yuan Yao, Cong Wang, Michele S Redell, Shuo Dong, Yongcheng Song.   

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.

Entities:  

Year:  2013        PMID： 23795283      PMCID： PMC3686528          DOI： 10.1039/C3MD00021D

Source DB:  PubMed          Journal:  Medchemcomm        ISSN： 2040-2503            Impact factor:   3.597


  21 in total

1.  Comparison of the use of liver models for predicting drug clearance using in vitro kinetic data from hepatic microsomes and isolated hepatocytes.

Authors:  Kiyomi Ito; J Brian Houston
Journal:  Pharm Res       Date:  2004-05       Impact factor: 4.200

Review 2.  Chemical probes for histone-modifying enzymes.

Authors:  Philip A Cole
Journal:  Nat Chem Biol       Date:  2008-10       Impact factor: 15.040

Review 3.  The epigenomics of cancer.

Authors:  Peter A Jones; Stephen B Baylin
Journal:  Cell       Date:  2007-02-23       Impact factor: 41.582

4.  Structural snapshots of MTA/AdoHcy nucleosidase along the reaction coordinate provide insights into enzyme and nucleoside flexibility during catalysis.

Authors:  Jeffrey E Lee; G David Smith; Cathy Horvatin; David J T Huang; Kenneth A Cornell; Michael K Riscoe; P Lynne Howell
Journal:  J Mol Biol       Date:  2005-09-23       Impact factor: 5.469

5.  Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.

Authors:  Qin Feng; Hengbin Wang; Huck Hui Ng; Hediye Erdjument-Bromage; Paul Tempst; Kevin Struhl; Yi Zhang
Journal:  Curr Biol       Date:  2002-06-25       Impact factor: 10.834

6.  Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.

Authors:  Wenyu Yu; Emma J Chory; Amy K Wernimont; Wolfram Tempel; Alex Scopton; Alexander Federation; Jason J Marineau; Jun Qi; Dalia Barsyte-Lovejoy; Joanna Yi; Richard Marcellus; Roxana E Iacob; John R Engen; Carly Griffin; Ahmed Aman; Erno Wienholds; Fengling Li; Javier Pineda; Guillermina Estiu; Tatiana Shatseva; Taraneh Hajian; Rima Al-Awar; John E Dick; Masoud Vedadi; Peter J Brown; Cheryl H Arrowsmith; James E Bradner; Matthieu Schapira
Journal:  Nat Commun       Date:  2012       Impact factor: 14.919

7.  Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L.

Authors:  Justin L Anglin; Lisheng Deng; Yuan Yao; Guobin Cai; Zhen Liu; Hong Jiang; Gang Cheng; Pinhong Chen; Shuo Dong; Yongcheng Song
Journal:  J Med Chem       Date:  2012-09-06       Impact factor: 7.446

8.  Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group.

Authors:  Joanne M Hilden; Patricia A Dinndorf; Sharon O Meerbaum; Harland Sather; Doojduen Villaluna; Nyla A Heerema; Ron McGlennen; Franklin O Smith; William G Woods; Wanda L Salzer; Helen S Johnstone; Zoann Dreyer; Gregory H Reaman
Journal:  Blood       Date:  2006-03-23       Impact factor: 22.113

9.  S-adenosylmethionine metabolism in HL-60 cells: effect of cell cycle and differentiation.

Authors:  P Chiba; C Wallner; E Kaiser
Journal:  Biochim Biophys Acta       Date:  1988-08-19

10.  Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies.

Authors:  Yuan Yao; Pinhong Chen; Jiasheng Diao; Gang Cheng; Lisheng Deng; Justin L Anglin; B V Venkataram Prasad; Yongcheng Song
Journal:  J Am Chem Soc       Date:  2011-10-04       Impact factor: 16.383
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  16 in total

1.  Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach.

Authors:  Chao Chen; Hugh Zhu; Frédéric Stauffer; Giorgio Caravatti; Susanne Vollmer; Rainer Machauer; Philipp Holzer; Henrik Möbitz; Clemens Scheufler; Martin Klumpp; Ralph Tiedt; Kim S Beyer; Keith Calkins; Daniel Guthy; Michael Kiffe; Jeff Zhang; Christoph Gaul
Journal:  ACS Med Chem Lett       Date:  2016-06-01       Impact factor: 4.345

2.  A convergent synthesis of carbocyclic sinefungin and its C5 epimer.

Authors:  Arun K Ghosh; Kai Lv
Journal:  European J Org Chem       Date:  2014-10-01

Review 3.  Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond.

Authors:  Chun-Wei Chen; Scott A Armstrong
Journal:  Exp Hematol       Date:  2015-06-25       Impact factor: 3.084

Review 4.  A chemical probe toolbox for dissecting the cancer epigenome.

Authors:  Jake Shortt; Christopher J Ott; Ricky W Johnstone; James E Bradner
Journal:  Nat Rev Cancer       Date:  2017-02-23       Impact factor: 60.716

5.  Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket.

Authors:  Clemens Scheufler; Henrik Möbitz; Christoph Gaul; Christian Ragot; Céline Be; César Fernández; Kim S Beyer; Ralph Tiedt; Frédéric Stauffer
Journal:  ACS Med Chem Lett       Date:  2016-06-06       Impact factor: 4.345

6.  3-(Piperidin-4-ylmethoxy)pyridine Containing Compounds Are Potent Inhibitors of Lysine Specific Demethylase 1.

Authors:  Fangrui Wu; Chao Zhou; Yuan Yao; Liping Wei; Zizhen Feng; Lisheng Deng; Yongcheng Song
Journal:  J Med Chem       Date:  2015-12-24       Impact factor: 7.446

Review 7.  A medicinal chemistry perspective for targeting histone H3 lysine-79 methyltransferase DOT1L.

Authors:  Justin L Anglin; Yongcheng Song
Journal:  J Med Chem       Date:  2013-08-14       Impact factor: 7.446

8.  Identification of DOT1L inhibitors by structure-based virtual screening adapted from a nucleoside-focused library.

Authors:  Garrett S Gibbons; Amarraj Chakraborty; Sierrah M Grigsby; Afoma C Umeano; Chenzhong Liao; Omar Moukha-Chafiq; Vibha Pathak; Bini Mathew; Young-Tae Lee; Yali Dou; Stephan C Schürer; Robert C Reynolds; Timothy S Snowden; Zaneta Nikolovska-Coleska
Journal:  Eur J Med Chem       Date:  2020-01-02       Impact factor: 6.514

Review 9.  SAM/SAH Analogs as Versatile Tools for SAM-Dependent Methyltransferases.

Authors:  Jing Zhang; Yujun George Zheng
Journal:  ACS Chem Biol       Date:  2015-11-16       Impact factor: 5.100

10.  Structure-guided DOT1L probe optimization by label-free ligand displacement.

Authors:  Joanna S Yi; Alexander J Federation; Jun Qi; Sirano Dhe-Paganon; Michael Hadler; Xiang Xu; Roodolph St Pierre; Anthony C Varca; Lei Wu; Jason J Marineau; William B Smith; Amanda Souza; Emma J Chory; Scott A Armstrong; James E Bradner
Journal:  ACS Chem Biol       Date:  2015-01-15       Impact factor: 5.100
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