Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799
J Ohwada, H Ebiike, H Kawada, M Tsukazaki… - Bioorganic & medicinal …, 2011 - Elsevier
J Ohwada, H Ebiike, H Kawada, M Tsukazaki, M Nakamura, T Miyazaki, K Morikami…
Bioorganic & medicinal chemistry letters, 2011•ElsevierPhosphatidylinositol 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 (IC50=
0.014 μM). In human tumor cell lines with PI3K pathway activation, CH5132799 showed …
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 (IC50=
0.014 μM). In human tumor cell lines with PI3K pathway activation, CH5132799 showed …
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 (IC50=0.014μM). 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.
Elsevier