XL413 and Neoplasms

XL413 has been researched along with Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for XL413 and Neoplasms

Article	Year
Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorganic & medicinal chemistry letters, 2012, Jun-01, Volume: 22, Issue:11 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. Topics: Animals; Binding Sites; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Line, Tumor; Computer Simulation; Humans; Mice; Neoplasms; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Pyrimidinones; Rats; Structure-Activity Relationship; Transplantation, Heterologous; Up-Regulation	2012

Article

Year

Discovery of XL413, a potent and selective CDC7 inhibitor.

Bioorganic & medicinal chemistry letters, 2012, Jun-01, Volume: 22, Issue:11

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.

Topics: Animals; Binding Sites; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Line, Tumor; Computer Simulation; Humans; Mice; Neoplasms; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Pyrimidinones; Rats; Structure-Activity Relationship; Transplantation, Heterologous; Up-Regulation

2012