Discovery of XL413, a potent and selective CDC7 inhibitor

Bioorganic & Medicinal Chemistry Letters
Elena S KoltunPatrick C Kearney

Abstract

CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model.

References

Jul 22, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alessia MontagnoliFrancesco Colotta
May 1, 2012·Bioorganic & Medicinal Chemistry Letters·Amy Lew TsuhakoWei Xu

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Citations

Oct 16, 2012·Nature Structural & Molecular Biology·Siobhan HughesPeter Cherepanov
May 6, 2014·European Journal of Medicinal Chemistry·Andreas ReicheltJennifer H Dao
Jun 5, 2013·Chemistry : a European Journal·Jens MaesBert U W Maes
Apr 4, 2013·Cell Cycle·Lindsay A Matthews, Alba Guarné
May 21, 2014·Cell Cycle·Masayuki YamadaJiri Bartek
Jul 14, 2016·Nucleic Acids Research·Kevin Z L WuCorrado Santocanale
Dec 16, 2016·Journal of Medicinal Chemistry·Lai WeiYe Fang
Feb 15, 2017·The Journal of Organic Chemistry·Shin KamijoToshihiro Murafuji
Jun 1, 2017·ACS Chemical Biology·Michael D RaineyCorrado Santocanale
Apr 11, 2018·Oncogene·Jingwen ZhangHuawei Chen
May 25, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Michael J PodolskyKamran Atabai
Dec 3, 2014·The Journal of Biological Chemistry·Robert StephensonVikki M Weake
May 2, 2020·Nature Communications·Beeke WienertJacob E Corn
Nov 29, 2016·Cancer Cell International·Zubeyde ErbayraktarErdogan Pekcan Erkan
May 2, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Shufang JinZhiyuan Zhang
Jun 10, 2020·Nature Communications·Thomas L Maurissen, Knut Woltjen
Aug 1, 2018·Cell & Bioscience·Liangru Fei, Hongtao Xu
Aug 14, 2019·Frontiers in Immunology·Elijah W ChenVasily Rybakin
Apr 8, 2020·Acta Crystallographica. Section F, Structural Biology Communications·Manon DemulderRemy Loris
Sep 3, 2020·Cell Reports·Michael D RaineyCorrado Santocanale
Feb 14, 2021·Drug Discovery Today·Christian Bailly, Gérard Vergoten
Jan 16, 2021·Cancer Cell·Liang ChangWilliam R Sellers
Jun 11, 2020·Structure·Samual D DickPeter Cherepanov
Apr 24, 2021·Cancer Cell·Jan M SuskiPiotr Sicinski
Oct 6, 2021·Journal of Medicinal Chemistry·Takayuki IrieMasaaki Sawa
Nov 26, 2021·Drug Discovery Today·Siwei ChenHidde J Haisma

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