Pictilisib 957054-30-7

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Pictilisib (GDC-0941) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Phase 2.

GDC-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. [1] 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. [2] GDC-0941 significantly inhibits the growth of HCT116, DLD1 and HT29 cells with GI50 of 1081 nM, 1070 nM and 157 nM, respectively. [3] GDC-0941 inhibits tumor cell proliferation, induces apoptosis and suppresses centroblast population. [4]

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