GDC-0077

Description

Inavolisib, or GDC-0077, is a potent and selective PI3K inhibitor. GDC-0077 blocks an enzyme involved in cancer growth called PI3K. GDC0077 binds to and inhibits various members of the PI3K family, including activating mutations in the catalytic alpha isoform PIK3CA. PI3K inhibition prevents the activation of the PI3K-mediated signaling pathway and inhibits the growth and survival of PI3K-overexpressing tumor cells. The IUPAC name of this compound is (S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino)propanamide.

in vitro

GDC-0077 (RG6114) 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. GDC-0077 selectively degrades mutant PI3Kα in a proteasome-dependent fashion, resulting in a 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.