LY-294002 hydrochloride 是一种合成的 PI3Kα/δ/β 分子抑制剂（IC50：0.5/0.57/0.97 μM，在无细胞试验中）；在溶液中比 Wortmannin 更稳定，也是自噬体形成的阻断剂。

LY294002 is a synthetic molecule inhibitor of PI3Kα/δ/β (IC50: 0.5/0.57/0.97 μM, in cell-free assays); more stable than Wortmannin in solution, and also is a blocker of autophagosome formation.

LY294002 inactivates Akt/PKB, consequently inhibiting cell proliferation and inducing apoptosis. In these colon cancer cell lines, LY294002 shows a remarkable growth-inhibitory and apoptosis-inducing effect and decreases expression of phosphorylated Akt (Ser473)[2]. LY294002 induces diminished cytoplasmic volume and obvious nuclear pyknosis in the tumor cells. LY294002 induces specific G1 arrest in cell growth, leading to almost complete inhibition of melanoma cell proliferation and partial inhibition of MG-63 (osteosarcoma cell line) proliferation[3].

LY294002 can suppress tumor growth and induce apoptosis, especially in the LoVo tumors. Thus, It shows remarkable effectiveness in the mouse peritonitis carcinoma tosa model [2]. LY294002 markedly inhibits growth and ascites formation of ovarian carcinoma [3].

PI3K inhibition by LY294002 is determined in a radiometric assay using purified, recombinant enzymes with 1 μM ATP. The kinase reaction is carried out for 1 hour at room temperature (24oC) and is terminated by addition of PBS. IC50 values are subsequently determined using a sigmoidal dose-response curve fit (variable slope). CK2 and GSK3β (glycogen synthase kinase 3β) inhibition are established by kinase selectivity screening. LY294002 is tested against the Upstate panel of kinases in 10 μM ATP.[4]

Cell lines: Colon cancer cell lines DLD-1,LoVo,HCT15,and Colo205. Concentrations: 0–50 μM. Incubation Time: 0–48 hours. Method: 1.0×105 cells (100 μL volume/well) are inoculated into 96-well microtiter plates.LY294002 is added to triplicate wells and cultured at 37oC for 0–48 hours.After treatment,Premix WST-1 (10 μL) is added to each microculture well,and the plates are incubated for 60 minutes at 37oC,after which absorbance at 450 nm is measured with a microplate reader.[2]

Animal Models: Two groups of athymic nude mice (5–7 weeks) are inoculated i.p.with OVCAR-3 cells. Formulation: Dissolved in DMSO plus 0.25 ml of PBS. Dosages: 0–100 mg/kg. Administration: i.p.[3]

934389-88-5

C19H18ClNO3

343.81

LY 294002;NSC 697286;SF 1101

Ethanol:5 mM
DMSO:25 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years