产品说明
一般描述
A cell-permeable thienopyrrolopyridazinone that acts as a potent allosteric PKM2 activator (AC50 = 92 nM; [PKM2] = 0.1 nM) via stoichiometric interaction (Two activator molecules per tetramer) with FBP-bound PKM2 tetramer (One FBP per monomer) in a similar manner as PKM2 Activator III (Cat. No. 504537), resulting in highly stabilized PKM2 tetramer resistant to dissociation in the presence of phosphotyrosine-containing peptide/protein or upon PKM2 K305Q mutation. Reported to exhibit good aqueous solubility (29.6 µg/mL or 79.5 µM in PBS, pH 7.4) and retard human lung carcinoma H1299 proliferation under hypoxia, but not normoxia, condition in cultures (doubling time = 50 and 35 h, respectively, with or without 30 µM TEPP-46; 1% O2) in vitro. TEPP-46 is bioavailable in mice via i.p. (Tmax = 0.5 h; Cmax = 10.854 µg/mL; AUCINF = 26.994 hr·µg/mL; 10 mg/kg) or p.o. (Tmax = 0.25 h; Cmax = 10.179 µg/mL; AUCINF = 24.350 hr·µg/mL; 10 mg/kg) administration and shown to impair H1299 tumorigenesis in mice (%tumor development/av. tumor weight = 30%/0.13 mg and 70%/2.6 mg, respectively, with or without 50 mg/kg/12 h oral dosage for 7 wks) in vivo with no apparent toxicity.
A cell-permeable thienopyrrolopyridazinone that exhibits good aqueous solubility (29.6 µg/mL or 79.5 µM in PBS, pH 7.4) and acts as a potent allosteric PKM2 activator (AC50 = 92 nM; [PKM2] = 0.1 nM) by stabilizing PKM2 tetramer via stoichiometric interaction with FBP-bound PKM2 (2 activator/4 FBP/tetramer) in a similar manner as PKM2 Activator III (Cat. No. 504537). Reprorted to retard human lung carcinoma H1299 proliferation under hypoxia, but not normoxia, condition in cultures (doubling time = 50 and 35 h, respectively, with or without 30 µM TEPP-46; 1% O2) in vitro and impair H1299 tumorigenesis in mice (50 mg/kg/12 h p.o.) in vivo with no apparent toxicity.
包装
5 mg in Glass bottle
Packaged under inert gas
生化/生理作用
Cell permeable: yes
Primary Target
PKM2
Reversible: yes
警告
Toxicity: Standard Handling (A)
重悬
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Use only fresh DMSO for reconstitution.
其他说明
Anastasiou, D., et al. 2012. Nat. Chem. Biol.8, 839.
Jiang, J.K., et al. 2010. Bioorg. Med. Chem. Lett.20, 3387.
法律信息
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
基本信息
经验(实验)分子式 | C17H16N4O2S2 |
分子量 | 372.46 |
产品性质
质量水平 | 100 |
测定 | ≥98% (HPLC) |
形式 | solid |
manufacturer/tradename | Calbiochem® |
储存条件 | OK to freeze protect from light |
颜色 | white |
溶解性 | DMSO: 100 mg/mL |
运输 | ambient |
储存温度 | 2-8℃ |
安全信息
储存分类代码 | 11 - Combustible Solids |
WGK | WGK 3 |
闪点(F) | Not applicable |
闪点(C) | Not applicable |