LY303511

Description: LY303511 is an analog of LY294002 and is also known as NV-128 and EM 101. Unlike LY294002 which is a BET/PI3K inhibitor, LY303511 is a potent mTOR inhibitor. LY303511 inhibits mTOR-dependent cell proliferation without unwanted effects on PI3K. In human lung epithelial adenocarcinoma (A549) cells, LY303511, like rapamycin, inhibited mTOR-dependent phosphorylation of S6K, but not PI3K-dependent phosphorylation of Akt. LY303511 blocked proliferation in A549 as well as in primary pulmonary artery smooth muscle cells, without causing apoptosis. In contrast to rapamycin, LY303511 reduced G(2)/M progression as well as G(2)/M-specific cyclins in A549 cells. Consistent with an additional mTOR-independent kinase target, LY303511 inhibited casein kinase 2 activity, a known regulator of G(1) and G(2)/M progression. In addition to its antiproliferative effect in vitro, LY303511 inhibited the growth of human prostate adenocarcinoma tumor implants in athymic mice. Given its inhibition of cell proliferation via mTOR-dependent and independent mechanisms, LY303511 has therapeutic potential with antineoplastic actions that are independent of PI3K inhibition.

References: J Pharmacol Exp Ther. 2005 Sep; 314(3):1134-43; Cancer Res. 2005 Jul 15; 65(14):6264-74.

Related CAS#: 854127-90-5 (2HCl); 2070014-90-1 (HCl)