Sigma-Aldrich DSM1 DHODH Inhibitor, 25mg

Assay

≥97% (HPLC)

Quality Level

100

Form

solid

Potency

15 nM K_i

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

off-white

Solubility

DMSO: 50 mg/mL

Storage Temp.

2-8°C

Smiles String

CC1=NC2=NC=NN2C(=C1)NC3=CC4=CC=CC=C4C=C3

General Description

A cell-permeable triazolopyrimidine compound that potently inhibits malaria parasitePlasmodium falciparumdihydroorotate dehydrogenase- (PfDHODH-) catalyzed electron transfer from FMNH₂to Coenzyme Q₁₀(CoQ or ubiquinone) in a potent (IC₅₀= 47 nM), CoQ-competitive (K_i= 15 nM), and species-specific manner, without affectingPfDHODH-catalyzed electron transfer from DHO to FMN or the enzymatic activity of human DHODH (<5% inhibition at 100 µM). Reported to inhibit the proliferation ofP. falciparumparasites (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 forin vivouse due to reduced plasma exposure upon repeat dosing in mice.A cell-permeable triazolopyrimidine compound that potently inhibits malaria parasitePlasmodium falciparumdihydroorotate dehydrogenase- (PfDHODH-) catalyzed electron transfer from FMNH₂to Coenzyme Q₁₀(CoQ or ubiquinone) in a potent (IC₅₀= 47 nM), CoQ-competitive (K_i= 15 nM), and species-specific manner, without affectingPfDHODH-catalyzed electron transfer from DHO to FMN or the enzymatic activity of human DHODH (<5% inhibition at 100 µM). Reported to inhibit the proliferation ofP. falciparumparasites (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 forin vivouse 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.DHODH Inhibitor, DSM1, is a highly potent, competitive, tight-binding inhibitor of Plasmodium falciparum dihydroorotate dehydrogenase (IC₅₀ = 47 nM; K_i= 15 nM).

Biochem/Physiol Actions

Cell permeable: yesPrimary Target
Pf*DHODH

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

Guler, J.L., et al. 2013.PLoS Pathog. 9,e1003375.

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