TEPP-46

Cell permeable: yes

Primary Target
PKM2

Reversible: yes

Toxicity: Standard Handling (A)

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. (T_max = 0.5 h; C_max = 10.854 µg/mL; AUC_INF = 26.994 hr·µg/mL; 10 mg/kg) or p.o. (T_max = 0.25 h; C_max = 10.179 µg/mL; AUC_INF = 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.

Anastasiou, D., et al. 2012. Nat. Chem. Biol.8, 839.

Jiang, J.K., et al. 2010. Bioorg. Med. Chem. Lett.20, 3387.

Packaged under inert gas

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.

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