Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo

详细信息    查看全文

• 作者：Janeta Popovici-Muller ; Jeffrey O. Saunders ; Francesco G. Salituro ; Jeremy M. Travins ; Shunqi Yan ; Fang Zhao ; Stefan Gross ; Lenny Dang ; Katharine E. Yen ; Hua Yang ; Kimberly S. Straley ; Shengfang Jin ; Kaiko Kunii ; Valeria R. Fantin ; Shunan Zhang ; Qiongqun Pan ; Derek Shi ; Scott A. Biller ; Shinsan M. Su
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：October 11, 2012
• 年：2012
• 卷：3
• 期：10
• 页码：850-855
• 全文大小：339K
• 年卷期：v.3,no.10(October 11, 2012)
• ISSN：1948-5875

文摘

Optimization of a series of R132H IDH1 inhibitors from a high throughput screen led to the first potent molecules that show robust tumor 2-HG inhibition in a xenograft model. Compound 35 shows good potency in the U87 R132H cell based assay and 90% tumor 2-HG inhibition in the corresponding mouse xenograft model following BID dosing. The magnitude and duration of tumor 2-HG inhibition correlates with free plasma concentration.

Keywords:

g/action/doSearch?action=search&searchText=Mutant+IDH1&qsSearchArea=searchText">Mutant IDH1; g/action/doSearch?action=search&searchText=tumor+2%5C-HG&qsSearchArea=searchText">tumor 2-HG; g/action/doSearch?action=search&searchText=R132H+IDH1+inhibitors&qsSearchArea=searchText">R132H IDH1 inhibitors