CNX-1351,1276105-89-5

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CNX-1351

CAS No. : 1276105-89-5

MCE 国际站：CNX-1351

产品活性：CNX-1351 是一种有效的选择性 PI3Kα 抑制剂，IC₅₀ 为 6.8 nM。

研究领域：PI3K/Akt/mTOR

作用靶点：PI3K

In Vitro: CNX-1351 is able to potently (EC₅₀<100 nM) and specifically inhibit signaling in PI3Kα-dependent cancer cell lines, and this leads to a potent antiproliferative effect (GI₅₀<100 nM). CNX-1351 inhibits PI3K signaling in SKOV3 cells, with potency (EC₅₀ 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 (GI₅₀ of 78 and 55 nM, respectively).

In Vivo: CNX-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.

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