Pictilisib (GDC-0941)

InformationPictilisib (GDC-0941, RG7321) is a potent inhibitor ofPI3Kα/δwithIC50of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) inducesautophagyandapoptosis. Phase 2.In vitroGDC-0941 is equipotent against PI3Kα and PI3Kδ as well as PI3Kα mutants E545-K and H1047-R, displaying modest levels of selectivity against PI3Kβ (10-fold) and PI3Kγ (25-fold), and greater levels of selectivity against members of PI3K class II, III, and IV, including C2β, Vps34, DNA-PK, and mTOR. GDC-0941 potently inhibits the phosphorylation of Akt in U87MG, PC3, and MDA-MB-361 cells with IC50 of 46 nM, 37 nM, and 28 nM, respectively. GDC-0941 inhibits the proliferation of U87MG, A2780, PC3, and MDA-MB-361 cells with IC50 of 0.95 μM, 0.14 μM, 0.28 μM, and 0.72 μM, respectively. GDC-0941 treatment potently inhibits the proliferation of both trastuzumab-sensitive and -insensitive HER2-amplified cells with IC50 of 149-944 nM. GDC-0941 inhibits proliferation of HER2-amplified cells that harbor PIK3CA mutations with IC50 of <500 nM, and effectively inhibits both proliferation and viability of HER2-amplified breast cancer cells that are resistant to trastuzumab due to PTEN loss. GDC-0941 significantly inhibits the growth of HCT116, DLD1 and HT29 cells with GI50 of 1081 nM, 1070 nM and 157 nM, respectively. GDC-0941 inhibits tumor cell proliferation, induces apoptosis and suppresses centroblast population.In vivoGDC-0941 shows limited microsomal metabolism, resulting in 78% oral bioavailability . Administration of GDC-0941 at 75 mg/kg/day displays significant inhibitory effect against established human U87MG glioblastoma xenografts in female NCr athymic mice, with tumor growth inhibition of 83%. Oral administration of GDC-0941 at 150 mg/kg/day inhibits the growth of HER2-amplified, trastuzumab-resistant MDA-MB-361.1 xenografts in mice, and significantly delays the tumor progression, in association with potent induced apoptosis in tumors. GDC-0941 (75 mg/kg/day) treatment for 2 weeks induces ~40% reduction in tumor volume of spontaneous B-cell follicular lymphomas developed in PTEN+/-LKB1+/hypo mice, accompanied by ablation of phosphorylation of Akt, S6K and SGK (serum and glucocorticoid protein kinase) protein kinases.Cell Datacell lines：293/CB2 cells with [3H]adenine (1 μCi/mL)Concentrations：Dissolved in DMSO, final concentrations ~10 μMIncubation Time：48 and 72 hoursPowder Purity:≥97%.

Specifications and Purity: 10mM in DMSO

Molecular Formula: C23H27N7O3S2

Molecular Weight: 513.64