Potent PI3K inhibitor
CAS：154447-36-6
分子式：C19H17NO3
分子量：307.34
纯度：＞99%
存储：Store at -20°C

Background:

LY294002 is a potent inhibitor of class I phosphoinositide 3-kinases (PI3Ks) [1, 2]. It is cell permeable and reversible, and selective against p110α, p110β, p110γ and p110δ, which acts on ATP binding site of the catalytic subunit.

PI3K family is divided into 3 classes: class I, II and III. LY294002 can inhibit 3 out of 4 isoforms of catalytic subunit of class I group. The IC50s for p110α, β andδ are 500 nM, 973 nM and 570 nM [3]. Even though it is less potent than wortmannin, other PI3K inhibitor, but it is more stable in solution. In addition, LY294002 is a reversible inhibitor whereas wortmannin acts irreversibly. [2]

PI3Ks signal through Akt, activates mTOR and inhibits Bad, leading to cell growth and proliferation. LY294002 potently inactivates PI3K class I catalytic subunit, resulting in induction of apoptosis and suppression of tumor cell growth in vitro and in vivo. [2, 4]

LY294002 is also a potent autophagy inhibitor by blocking autophagosome formation. [5]

Quantitative chemoproteomic profiling shows that LY294002 inhibits the BET bromodomain proteins BRD2, BRD3, and BRD4 with IC50 value of 1-2 μM. [6]

参考文献:
[1]Maira et al. (2009). PI3K inhibitors for cancer treatment: where do we stand?. doi:10.1042/BST0370265.
[2]Vlahos CJ., et al. (1994). A Specific Inhibitor of Phosphatidylinositol 3-Kinase, 2-(4-Morpholinyl)-8-phenyl-4H-l-benzopyran-4-one (LY294002). Journal of Biological Chemistry 269 (7): 5241–5248.
[3]Chaussade C, et al. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J, 2007, 404(3), 449-58.
[4]Hu L, et al. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). Clin Cancer Res, 2000, 6(3), 880-6.
[5]Blommaart EF., et al., (1997). The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur. J. Biochem. 243: 240–246.
[6]Dittmann, A., et al. (2013). The Commonly Used PI3-Kinase Probe LY294002 is an Inhibitor of BET Bromodomains. ACS Chemical Biology: 131210150813004.