product name Vidofludimus
Description: Vidofludimus, also known as 4SC 101 or SC12267, is a novel orally active and potent dihydroorotate dehydrogenase (DHODH) inhibitor with IC50 of 134 nM for human DHODH. In vitro, 4SC-101 is a potent inhibitor of human DHODH, inhibits lymphocyte proliferation, and uniquely blocks phytohemagglutinin-stimulated IL-17 production by lymphocytes. In vivo, oral administration of 4SC-101 effectively improved both chronic DSS and acute TNBS colitis in mice.
References: Am J Pathol. 2010 Jun;176(6):2840-7; J Pharmacol Exp Ther. 2012 Sep;342(3):850-60.
355.36
Formula
C20H18FNO4
CAS No.
717824-30-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (281.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
SC12267, 4SC-101
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/1941018
| In Vitro |
In vitro activity: Vidofludimus causes a concentration dependent inhibition of phytohemagglutinin-stimulated PBMC proliferation via the inhibition of pyrimidine de novo synthesis. Vidofludimus attenuates IL-17 secretion from colonic strips by inhibition of STAT3 and NF-κB activation. Kinase 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. Cell Assay: Vidofludimus (4SC-101, SC12267) has been reported to dose-dependently inhibit DHODH in an in vitro enzyme assay with IC50 values of 0.134μmol/L, 1.29μmol/L, 10.6μmol/L and 12.9μmol/L in human DHODH, rat DHODH, mouse DHODH and human PBMC, respectively. In addition, Vidofludimus has shown the inhibition of proliferation in phytohemagglutinin-induced lymphocytes with an IC50 value of ~13μmol/L. Moreover, Vidofludimus has been revealed to concentration-dependently inhibit phytohemagglutinin-stimulated interukin-17 secretion from human peripgeral blppd mononuclear cell lines (PBMCs) with an IC50 value of 6 μmol/L. |
|---|---|
| In Vivo | In MRLlpr/lpr mice, Vidofludimus (300 mg/kg, p.o.) reduces systemic autoimmunity and improves Lupus Nephritis. In Rats, Vidofludimus (60 mg/kg, p.o.) effectively reduces macroscopic and histological pathology and the numbers of CD3+ T cells. In a rat model of renal transplantation, Vidofludimus (20 mg/kg, p.o.) prolongs survival, paralleled by amelioration of histologic signs of acute rejection |
| Animal model | MRLlpr/lpr mice |
| Formulation & Dosage | Suspended in water; 300 mg/kg; p.o. administration |
| References | Am J Pathol. 2010 Jun;176(6):2840-7; J Pharmacol Exp Ther. 2012 Sep;342(3):850-60. |
