DHODH Inhibitor; DSM1 1PC X 25MG

Biochem/physiol Actions

Primary TargetPf*DHODH

Cell permeable: yes

General description

A cell-permeable triazolopyrimidine compound that potently inhibits malaria parasite Plasmodium falciparum dihydroorotate dehydrogenase- (PfDHODH-) catalyzed electron transfer from FMNH₂ to Coenzyme Q₁₀ (CoQ or ubiquinone) in a potent (IC₅₀ = 47 nM), CoQ-competitive (K_i = 15 nM), and species-specific manner, without affecting PfDHODH-catalyzed electron transfer from DHO to FMN or the enzymatic activity of human DHODH (﹤5% inhibition at 100 µM). Reported to inhibit the proliferation of P. falciparum parasites (EC₅₀ = 79 nM against 3D7 strain) in vitro, including the drug-resistant strain Dd2 (EC₅₀ = 140 nM), while displaying no inhibitory potency against murine lymphocytic leukemia cell line L1210 even at concentrations as high as 10 µM. DSM1 is not recommended for in vivo use due to reduced plasma exposure upon repeat dosing in mice.

DHODH Inhibitor, DSM1, is a highly potent, competitive, tight-binding inhibitor of Plasmodium falciparum dihydroorotate dehydrogenase (IC₅₀ = 47 nM; K_i = 15 nM).

A cell-permeable triazolopyrimidine compound that potently inhibits malaria parasite Plasmodium falciparum dihydroorotate dehydrogenase- (PfDHODH-) catalyzed electron transfer from FMNH₂ to Coenzyme Q₁₀ (CoQ or ubiquinone) in a potent (IC₅₀ = 47 nM), CoQ-competitive (K_i = 15 nM), and species-specific manner, without affecting PfDHODH-catalyzed electron transfer from DHO to FMN or the enzymatic activity of human DHODH (﹤5% inhibition at 100 µM). Reported to inhibit the proliferation of P. falciparum parasites (EC₅₀ = 79 nM against 3D7 strain) in vitro, including the drug-resistant strain Dd2 (EC₅₀ = 140 nM), while displaying no inhibitory potency against murine lymphocytic leukemia cell line L1210 even at concentrations as high as 10 µM. DSM1 is not recommended for in vivo use due to reduced plasma exposure upon repeat dosing in mice.Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Guler, J.L., et al. 2013. PLoS Pathog.9, e1003375.r>Ke, H., et al. 2011. Eukaryot. Cell.10, 1053.Ganesan, S.M., et al. 2011. Mol. Biochem. Parasitol.177, 29.Booker, M.L., et al. 2010. J. Biol. Chem.285, 33054.Gujjar, R., et al. 2009. J. Med. Chem.52, 1864.Phillips, M.A., et al. 2008. J. Med. Chem.51, 3649.

Packaging

25 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Standard Handling (A)