CNX-1351 (C09-1120-042)

CNX-1351 is a potent and isoform-selective targeted covalent PI3Kα inhibitor with IC 50 of 6.8 nM.In VitroCNX-1351 is able to potently (EC 50 <100 nM) and specifically inhibit signaling in PI3Kα-dependent cancer cell lines, and this leads to a potent antiproliferative effect (GI 50 <100 nM). CNX-1351 inhibits PI3K signaling in SKOV3 cells, with potency (EC 50 of 10-100 nM) similar to that of the pan-PI3K inhibitor. To investigate the functional consequence of inhibiting PI3Kα in cells, two cell lines with different PIK3CA activating mutations, SKOV3 ovarian cancer cells (H1047R) and MCF-7 breast cancer cells (E545K), are treated with CNX-1351 and growth is monitored. Both PIK3CA -driven cell lines are growth inhibited by exposure to CNX-1351 for 96 h (GI 50 of 78 and 55 nM, respectively). MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoCNX-1351 inhibits p-Akt Ser473 in mouse spleens and bonds to PI3Kα in vivo. CNX-1351 is delivered into the intraperitoneal cavity of nude mice at 100 mg/kg once a day for 5 consecutive days (n=3 mice per group). Spleens are harvested from the mice at the indicated times after the last dose (1-24 h) and interrogated by immunoblot for P-Akt Ser473 or for PI3Kα occupancy. Inhibition of PI3K signaling is detected as a decrease in P-Akt Ser473 at 1 and 4 h after last dose . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:PI3Kα 6.8 nM (IC 50 ) PI3Kβ 166 nM (IC 50 ) PI3Kδ 240.3 nM (IC 50 ) PI3Kγ 3020 nM (IC 50 ). Specification: 0.99 Molecular Formula: C30H35N7O3S Molecular Weight: 573.71 PubChem CID: 58441401 Isomeric SMILES: CC(=CC(=O)CCC(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6)C