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Basic Information
ID: ALA1681712
Journal: Bioorg Med Chem Lett
Title: Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799.
Authors: Ohwada J, Ebiike H, Kawada H, Tsukazaki M, Nakamura M, Miyazaki T, Morikami K, Yoshinari K, Yoshida M, Kondoh O, Kuramoto S, Ogawa K, Aoki Y, Shimma N.
Abstract: Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase and a promising therapeutic target for cancer. Using structure-based drug design (SBDD), we have identified novel PI3K inhibitors with a dihydropyrrolopyrimidine skeleton. Metabolic stability of the first lead series was drastically improved by replacing phenol with aminopyrimidine moiety. CH5132799, a novel class I PI3K inhibitor, exhibited a strong inhibitory activity especially against PI3Kα (IC(50)=0.014 μM). In human tumor cell lines with PI3K pathway activation, CH5132799 showed potent antiproliferative activity. CH5132799 is orally available and showed significant antitumor activity in PI3K pathway-activated human cancer xenograft models in mice.
CiteXplore: 21316229