PKM2 Activator IV, TEPP-46-Calbiochem

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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 ?g/mL or 79.5 ?M 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 ?M TEPP-46; 1% O₂)in vitro. TEPP-46 is bioavailable in mice via i.p. (T_max= 0.5 h;C_max= 10.854 ?g/mL;AUC_INF= 26.994 hr·?g/mL; 10 mg/kg) or p.o. (T_max= 0.25 h;C_max= 10.179 ?g/mL;AUC_INF= 24.350 hr·?g/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 vivowith no apparent toxicity.
A cell-permeable thienopyrrolopyridazinone that exhibits good aqueous solubility (29.6 ?g/mL or 79.5 ?M 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 ?M TEPP-46; 1% O₂)in vitroand impair H1299 tumorigenesis in mice (50 mg/kg/12 h p.o.)in vivowith 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

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