Description
LY303511 is a close structural analog of LY294002 , a selective phosphatidylinositol 3-kinase (PI3K) inhibitor.
1 LY303511, however, does not inhibit PI3K-dependent phosphorylation of Akt but instead has been shown to inhibit mTOR-dependent phosphorylation of S6K.
1 It can reduce cell proliferation in human lung epithelial adenocarcinoma cells, blocking G
2/M progression and inhibiting casein kinase 2 activity.
1 LY303511 demonstrates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitizing activity in HeLa cells that are refractory to TRAIL-induced apoptosis.
2 LY303511 is also reported to block voltage-gated potassium (K
v) channels.
3
References
1. Kristof, A.S., Pacheco-Rodriguez, G., Schremmer, B., et al. LY303511 (2-piperazinyl-8-phenyl-4H-1-benzopyran-4-one) acts via phosphatidylinositol 3-kinase-independent pathways to inhibit cell proliferation via mammalian target of rapamycin (mTOR)- and non-mTOR-dependent mechanisms J. Pharmacol. Exp. Ther. 314(3),1134-1143(2005).
2. Mellier, G., Liu, D., Bellot, G., et al. Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27 Cell Death Dis. 4,e890(2013).
3. Pattnaik, B.R., and Hughes, B.A. Regulation of Kir channels in bovine retinal pigment epithelial cells by phosphatidylinositol 4,5-bisphosphate Am. J. Physiol. Cell Physiol. 297(4),C1001-C1011(2009).
