GDC-0077 是一种可口服的选择性PI3Kα抑制剂，IC50值为0.038 nM。它通过与 PI3K 的 ATP 结合位点结合而发挥其活性，从而抑制了 PIP2 到 PIP3 的磷酸化。

GDC-0077 is an orally available and selective inhibitor of PI3Kα (IC50=0.038 nM). GDC-0077 is more selective for mutant versus wild-type PI3Kα. GDC-0077 exerts its activity by binding to the ATP binding site of PI3K, thereby inhibiting the phosphorylation of PIP2 to PIP3.

GDC-0077 is >300-fold more selective for PI3Kα over the other class I PI3K isoforms (β, δ, and γ). GDC-0077 is >2000-fold more selective over PIK family members. GDC-0077 selectively degrades mutant PI3Kα in a proteasome-dependent fashion. When compared to PIK3CA wild-type cells, it results in a reduction of PI3K pathway activity biomarkers such as pAKT and pPRAS40, inhibition of cell proliferation. It also increased apoptosis in human PIK3CA-mutant breast cancer cell lines to a greater extent [1].

In patient-derived PIK3CA-mutant breast cancer xenograft models, GDC-0077 (p.o.) causes tumor regressions, induction of apoptosis, and a reduction of pAKT, pPRAS40, and pS6RP in a dose-dependent fashion [1].

2060571-02-8

C18H19F2N5O4

407.37

RG6114;GDC-0077

DMSO:100 mg/mL (245.48 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years