1380495-85-1Relevant academic research and scientific papers
Discovery of XL413, a potent and selective CDC7 inhibitor
Koltun, Elena S.,Tsuhako, Amy Lew,Brown, David S.,Aay, Naing,Arcalas, Arlyn,Chan, Vicky,Du, Hongwang,Engst, Stefan,Ferguson, Kim,Franzini, Maurizio,Galan, Adam,Holst, Charles R.,Huang, Ping,Kane, Brian,Kim, Moon H.,Li, Jia,Markby, David,Mohan, Manisha,Noson, Kevin,Plonowski, Arthur,Richards, Steven J.,Robertson, Scott,Shaw, Kenneth,Stott, Gordon,Stout, Thomas J.,Young, Jenny,Yu, Peiwen,Zaharia, Cristiana A.,Zhang, Wentao,Zhou, Peiwen,Nuss, John M.,Xu, Wei,Kearney, Patrick C.
scheme or table, p. 3727 - 3731 (2012/07/16)
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.
The design, synthesis, and biological evaluation of PIM kinase inhibitors
Tsuhako, Amy Lew,Brown, David S.,Koltun, Elena S.,Aay, Naing,Arcalas, Arlyn,Chan, Vicky,Du, Hongwang,Engst, Stefan,Franzini, Maurizio,Galan, Adam,Huang, Ping,Johnston, Stuart,Kane, Brian,Kim, Moon H.,Douglas Laird,Lin, Rui,Mock, Lillian,Ngan, Iris,Pack, Michael,Stott, Gordon,Stout, Thomas J.,Yu, Peiwen,Zaharia, Cristiana,Zhang, Wentao,Zhou, Peiwen,Nuss, John M.,Kearney, Patrick C.,Xu, Wei
scheme or table, p. 3732 - 3738 (2012/07/17)
A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure.
