LY-294,002 hydrochloride

LY294002 hydrochloride is a potent and broad-spectrum PI3K inhibitor, with IC50 values of 0.5, 0.57, and 0.97 μM for P110α, P110δ and P110β, respectively. LY294002 hydrochloride also inhibits CK2 with an IC50 of 98 nM. LY294002 hydrochloride can be used for pancreatic cancer research[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA-PK

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Signaling Pathways >> Cell Cycle/DNA Damage >> Casein Kinase

Signaling Pathways >> PI3K/Akt/mTOR >> DNA-PK

Signaling Pathways >> Stem Cell/Wnt >> Casein Kinase

CK2:0.098 μM (IC50)

CK2α2:3.869 μM (IC50)

LY294002 hydrochloride (0-75 μM; 24 hours and 48 hours) remarkably decreases human nasopharyngeal carcinoma CNE-2Z cells in a dose-dependent fashion[4]. LY294002 hydrochloride (0-75 μM; 24 hours and 48 hours ) induces CNE-2Z cells apoptosis rate in dose-dependent[4]. LY294002 hydrochloride (10-75 μM) significantly decreases p-Akt (S473) expression levels and up-regulates caspase-9 activity in CNE-2Z cells. Total Akt protein level is not difference with different concentration[4]. LY294002 hydrochloride (5, 10, 100 µM; for 2 hours) treatment partially suppresses Lysophosphatidic acid (LPA)-induced (20 µM; for 4 hours) nuclear translocation of YAP, accompanied by a reduction in p-AKT levels[6]. Cell Proliferation Assay Cell Line: CNE-2Z cells[4] Concentration: 0 μM, 10 μM, 25 μM, 50 μM, and 75 μM Incubation Time: 24 hours and 48 hours Result: Decreased CNE-2Z cells in a dose-dependent fashion. Apoptosis Analysis Cell Line: CNE-2Z cells[4] Concentration: 0 μM, 10 μM, 25 μM, 50 μM, and 75 μM Incubation Time: 24 hours and 48 hours Result: Induced apoptosis rate in a dose-dependent manner. Western Blot Analysis Cell Line: CNE-2Z cells[4] Concentration: 0 μM, 10 μM, 25 μM, 50 μM, and 75 μM Incubation Time: 24 hours and 48 hours Result: Decreased phosphorylated Akt (S473) expression levels were significantly, up-regulated caspase-9 activity in CNE-2Z cells in treated group.

LY294002 hydrochloride (10, 25, 50, 75 mg/kg; i.p.; twice weekly; for 4 weeks) significantly reduces mean NPC tumor burden in a dose-dependent manner. LY294002 (10, 25 mg/kg) is less effective in decreasing tumor burden[4]. LY294002 hydrochloride (1.2 mg/kg per day; i.p.; for 14 days) prevents Leptin (60 ug/kg)-induced adverse effects on spermatozoa in Sprague-Dawley rats[5]. Animal Model: Athymic nude mice (6-8 weeks) with CNE-2Z xenograft[4] Dosage: 10 mg/kg, 25 mg/kg, 50 mg/kg, and 75 mg/kg Administration: IP; twice weekly, for 4 weeks Result: Mean Nasopharyngeal carcinoma (NPC) tumor burden was remarkably decreased in a dose-dependent manner.

[1]. Bai R, et al. The effect of PI3K inhibitor LY294002 and gemcitabine hydrochloride combined with ionizing radiation on the formation of vasculogenic mimicry of Panc-1 cells in vitro and in vivo. Neoplasma. 2016;63(1):80-92.

[2]. Chaussade C, et al. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J. 2007 Jun 15;404(3):449-58.

[3]. Gharbi SI, et al. Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J. 2007 May 15;404(1):15-21.

[4]. Jiang H, et al. Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma invitro and in vivo. J Exp Clin Cancer Res. 2010 Apr 22;29:34.

[5]. Md Mokhtar AH, et al. LY294002, a PI3K pathway inhibitor, prevents leptin-induced adverse effects on spermatozoa in Sprague-Dawley rats. Andrologia. 2019 Apr;51(3):e13196.

[6]. Yi-Jen Hsueh, et al. Lysophosphatidic acid induces YAP-promoted proliferation of human corneal endothelial cells via PI3K and ROCK pathways. Mol Ther Methods Clin Dev. 2015 Apr 29;2:15014.