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VidofludiMus

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VidofludiMus Basic information

Product Name:
VidofludiMus
Synonyms:
  • VidofludiMus
  • SC12267)
  • VidofludiMus(4SC-101
  • VIDOFLUDIMUS(4SC-101; SC12267)
  • 2-[[(3-Fluoro-3'-methoxy[1,1'-biphenyl]-4-yl)amino]carbonyl]-1-cyclopentene-1-carboxylic acid
  • 2-[(3-Fluoro-3'-methoxy-4-biphenylyl)carbamoyl]-1-cyclopentene-1-carboxylic acid
  • 2-[(3-fluoro-3'-methoxybiphenyl-4-yl)carbamoyl]cyclopent-1-ene-1-carboxylic acid Vidofludimus(4SC-101
  • 4SC-101
CAS:
717824-30-1
MF:
C20H18FNO4
MW:
355.36
Product Categories:
  • API
  • Inhibitors
Mol File:
717824-30-1.mol
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VidofludiMus Chemical Properties

Boiling point:
567.5±50.0 °C(Predicted)
Density 
1.354±0.06 g/cm3(Predicted)
storage temp. 
Store at -20°C
solubility 
insoluble in H2O; insoluble in EtOH; ≥103 mg/mL in DMSO
form 
solid
pka
4?+-.0.20(Predicted)
color 
Light yellow to gray
InChI
InChI=1S/C20H18FNO4/c1-26-14-5-2-4-12(10-14)13-8-9-18(17(21)11-13)22-19(23)15-6-3-7-16(15)20(24)25/h2,4-5,8-11H,3,6-7H2,1H3,(H,22,23)(H,24,25)
InChIKey
XPRDUGXOWVXZLL-UHFFFAOYSA-N
SMILES
C1(C(O)=O)CCCC=1C(NC1=CC=C(C2=CC=CC(OC)=C2)C=C1F)=O
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Safety Information

WGK Germany 
WGK 3
Storage Class
11 - Combustible Solids
Hazard Classifications
Acute Tox. 4 Oral
Aquatic Acute 1
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VidofludiMus Usage And Synthesis

Uses

Vidofludimus is an immunosuppressive drug that inhibits dihydroorotate dehydrogenase (DHODH) and the expression of proinflammatory cytokines including interleukin-17 (IL17A and IL17F) and interferon-gamma.

Biological Activity

vidofludimus (4sc-101, sc12267) is a novel small molecule inhibitor of dihydroorotate dehydrogenase (dhodh) with an ic50 value of 134nmol/l for human dhodh [1].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 [1]. 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 [2].

in vivo

Vidofludimus (i.p.; once daily; for 14 days) exerts effects on dextran sodium sulfate (DSS) induced colitis in an FXR-dependent manner in vivo[1].
Vidofludimus (p.o; 60 mg/kg; for 6 days) effectively improves many parameters of TNBS-induced colitis in rats and has inhibitory effects on colonic STAT3 and IL-17[3].

Animal Model:homozygous FXR deficient (FXR KO) mice[1]
(10-week-old, male)
Dosage:20 mg/kg
Administration:oral, 20 mg/kg/day
Result:Revealed multifocal inflammatory cell infiltration and edema with crypt and epithelial cell destruction and ulceration.
Animal Model:NAFLD Model[1]
(10-11 weeks old male obese Lepob/ob C57BL/6 (ob/ob) mice)
Dosage:10 mg/kg
Administration:intraperitoneally, once daily, for 14 days
Result:Significantly reduced body weight loss, prevented colonic shortening, decreased histological scores, and disease activity index (DAI) scores in WT mice.
Significantly decreased colonic mRNA expression of the pro-inflammatorygenes interleukin (IL)-1β, IL-6, IL-17, and prostaglandin-endoperoxide synthase 2 (COX-2).
Animal Model:Wistar rats[3]
Dosage:60 mg/kg
Administration:p.o., for 6 days
Result:Effectively reduced macroscopic and histological pathology and the numbers of CD3+ T cells in vivo.
Reduced nuclear signal transducer and activator of transcription 3 (STAT3) binding and IL-17 levels.

IC 50

IL-17

References

[1] kulkarni op1, sayyed sg, kantner c, ryu m, schnurr m, sárdy m, leban j, jankowsky r, ammendola a, doblhofer r, anders hj. 4sc-101, a novel small molecule dihydroorotate dehydrogenase inhibitor, suppresses systemic lupus erythematosus in mrl-(fas) lpr mice. am j pathol. 2010 jun;176(6):2840-7.
[2] fitzpatrick lr1, deml l, hofmann c, small js, groeppel m, hamm s, lemstra s, leban j, ammendola a. 4sc-101, a novel immunosuppressive drug, inhibits il-17 and attenuates colitis in two murine models of inflammatory bowel disease. inflamm bowel dis. 2010 oct;16(10):1763-77.

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