PD0325901 | CAS:391210-10-9

Chemscene社は、高品質な低分子化合物を提供しているメーカーです。
Chemscene社のPD0325901(CAS:391210-10-9)をご紹介します。

※本製品は研究用です。研究用以外には使用できません。

Name:PD0325901; PD325901
Cat. No. :CS-0062
CAS No. :391210-10-9
Formula:C16H14F3IN2O4
M. Wt. : 482.19
Solubility:DMSO: ≥ 56 mg/mL

PD0325901 is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2.IC50 & Target: IC50: 0.33 nM (MEK)In Vitro: PF0325901 shows higher permeability, and should be able to achieve higher systemic exposures than CI-1040[1]. PD0325901 is exquisitely specific and highly potent against purified MEK, revealing a Kiapp of 1 nM against activated MEK1 and MEK2. PD0325901 is roughly 500-fold more potent than CI-1040 with respect to its cellular effects on phosphorylation of ERK1 and ERK2, displaying subnanomolar activity. PD0325901 prevents the growth of melanoma cell lines. PD0325901 inhibits the growth of TPC-1 cells and K2 cells with GC50 of 11 nM and 6.3 nM, respectively. PD0325901 significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM) and only moderately increases the growth of the PTC cells carrying the RET/PTC1 rearrangement at the same concentration. PD0325901 effectively inhibits the phosphorylation of ERK1/2 in multiple PTC cell lines[2]. In Vivo: PD0325901 (25 mg/kg, p.o.) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. The dose required to produce a 70% incidence of complete tumor responses (C26 model) is 25 mg/kg/day versus 900 mg/kg/day for PD0325901 and CI-1040, respectively. Anticancer activity of PD 0325901 has been demonstrated for a broad spectrum of human tumor xenografts. PD0325901 (20-25 mg/kg/day, p.o.) treatment in mice, shows no tumor growth inoculated with PTC cells bearing a BRAF mutation. For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor is decreased by 58% as compared with controls. PTC cells carrying a BRAF mutation are more sensitive to PD0325901 than are PTC cells carrying the RET/PTC1 rearrangement[2].

Henderson YC, et al. MEK inhibitor PD0325901 significantly reduces the growth of papillary thyroid carcinoma cells in vitro and in vivo. Mol Cancer Ther. 2010 Jul;9(7):1968-76. Barrett SD, et al. The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6501-4.