Vidofludimus (SC12267) (4SC-101, SC12267) is a novel small molecule inhibitor of dihydroorotate dehydrogenase (DHODH).

DHODH (human):134 nM

Vidofludimus causes a concentration dependent inhibition of phytohemagglutinin-stimulated PBMC proliferation via the inhibition of pyrimidine de novo synthesis. [1] Vidofludimus attenuates IL-17 secretion from colonic strips by inhibition of STAT3 and NF-κB activation. [2]

In MRLlpr/lpr mice, Vidofludimus (300 mg/kg, p.o.) reduces systemic autoimmunity and improves Lupus Nephritis. [1] In Rats, Vidofludimus (60 mg/kg, p.o.) effectively reduces macroscopic and histological pathology and the numbers of CD3+ T cells. [2] In a rat model of renal transplantation, Vidofludimus (20 mg/kg, p.o.) prolongs survival, paralleled by amelioration of histologic signs of acute rejection. [3]

DHODH inhibition assay: In vitro DHODH inhibition assay mixture contains 50 μM decycloubiquinone, 100 μM dihydroorotate, and 60 μM 2,6-dichloroindophenol. The amount of enzyme is adjusted such that an average slope of approximately 0.2 AU/min will be achieved in the assay for the positive control (eg, without inhibitor). Measurements are conducted in 50 mM TrisHCl, 150 mM KCl, 0.1% Triton X-100, and pH 8.0 at 30°C in a final volume of 1 ml. The components are mixed, and the reaction is started by adding dihydroorotate. The reaction is followed spectrophotometrically by measuring the decrease in absorption at 600 nm for 2 minutes. The assay is linear in time and enzyme concentration. Inhibitory studies are conducted in a standard assay with additional variable amounts of inhibitor. For the determination of the IC50 values (concentration of inhibitor required for 50% inhibition), eight different inhibitor concentrations are applied. Each data point is recorded in triplicates on a single measurement day.