| Literature DB >> 22560567 |
Elena S Koltun1, Amy Lew Tsuhako, David S Brown, Naing Aay, Arlyn Arcalas, Vicky Chan, Hongwang Du, Stefan Engst, Kim Ferguson, Maurizio Franzini, Adam Galan, Charles R Holst, Ping Huang, Brian Kane, Moon H Kim, Jia Li, David Markby, Manisha Mohan, Kevin Noson, Arthur Plonowski, Steven J Richards, Scott Robertson, Kenneth Shaw, Gordon Stott, Thomas J Stout, Jenny Young, Peiwen Yu, Cristiana A Zaharia, Wentao Zhang, Peiwen Zhou, John M Nuss, Wei Xu, Patrick 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.Entities:
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Year: 2012 PMID： 22560567 DOI： 10.1016/j.bmcl.2012.04.024
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823