idelalisib and Prostatic-Neoplasms

Phosphoinositide 3-kinase (PI3K) β signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation of a novel series of PI3Kβ/δ inhibitors in which PI3Kβ potency was built in a PI3Kδ-selective template. This work led to the discovery of a highly selective PI3Kβ/δ inhibitor displaying excellent pharmacokinetic profile and efficacy in a human PTEN-deficient LNCaP prostate carcinoma xenograft tumor model.

Topics: Animals; Cell Line, Tumor; Class Ia Phosphatidylinositol 3-Kinase; Dogs; Haplorhini; Humans; Male; Mice; Models, Molecular; Phosphoinositide-3 Kinase Inhibitors; Prostate; Prostatic Neoplasms; Protein Kinase Inhibitors; PTEN Phosphohydrolase; Rats; Rats, Sprague-Dawley