Inavolisib

Inavolisib (GDC-0077) is a potent, orally active, and selective PI3Kα inhibitor (IC₅₀=0.038 nM). Inavolisib exerts its activity by binding to the ATP binding site of PI3K, thereby inhibiting the phosphorylation of PIP2 to PIP3. Inavolisib is more selective for mutant versus wild-type PI3Kα. Inavolisib can be used for the study of breast cancer^[1]. IC50 & Target:IC50: 0.038 nM (PI3Kα)^[1] In Vitro:Inavolisib (GDC-0077) is >300-fold more selective for PI3Kα over the other class I PI3K isoforms (β, δ, and γ) and >2000-fold more selective over PIK family members. Inavolisib selectively degrades mutant PI3Kα in a proteasome-dependent fashion resulting in reduction of PI3K pathway activity biomarkers such as pAKT and pPRAS40, inhibition of cell proliferation, and increased apoptosis in human PIK3CA-mutant breast cancer cell lines to a greater extent when compared to PIK3CA wild-type cells^[1]. In Vivo:Inavolisib (p.o.) results in tumor regressions, induction of apoptosis, and a reduction of pAKT, pPRAS40, and pS6RP in a dose-dependent fashion in PIK3CA-mutant breast cancer xenograft models^[1].