| 產(chǎn)品描述： | Vidofludimus is an orally active inhibitor for dihydroorotate dehydrogenase (DHODH) and also is a novel modulator for farnesoid X receptor (FXR). Vidofludimus, as an immunomodulatory agent, can be used for the research of autoimmune disorders such as inflammatory bowel disease (IBD). Vidofludimus also can be used for the research of fatty liver by targeting FXR |
| 靶點： |
IL-17;Dehydrogenase;DNA/RNASynthesis;Interleukin |
| 體外研究： |
Vidofludimus (0-1 μM) selectively activats FXR in a concentration dependent manner with an EC50 value of about 450 nM in inducing the recruitment of various coactivator LXXLL motifs. Vidofludimus (0-8 μM) blocks nuclear translocation of p65 by suppressing IKK-IκB-NF-κB pathway. Vidofludimus has inhibitory activity for human DHODH with an IC50 value of 160 nM. Vidofludimus inhibits dihydro-orotate dehydrogenase and lymphocyte proliferation in vitro. Vidofludimus inhibits interleukin (IL)-17 secretion in vitro independently of effects on lymphocyte proliferation. Vidofludimus completely blocks IL-23 + IL-1β-stimulated secretion of IL-17 by colonic strips in ex vivo. Western Blot Analysis Cell Line: HepG2 cells or MEFs Concentration: 2, 8 μM Incubation Time: 1 h Result: Inhibited of TNFα-induced IKKα/β phosphorylation and IκBα degradation. RT-PCR Cell Line: HepG2 cells Concentration: 5 μM Incubation Time: 24 h Result: Inhibited the increase of NF-κB target genes MCP-1 and CXCL-2 upon TNFα stimulation. |
| 體內(nèi)研究： |
Vidofludimus (i.p.; once daily; for 14 days) exerts effects on dextran sodium sulfate (DSS) induced colitis in an FXR-dependent manner in vivo. 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. Animal Model: homozygous FXR deficient (FXR KO) mice(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(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 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. |
| 參考文獻(xiàn)： |
1. Yanlin Zhu, et al. Repositioning an Immunomodulatory Drug Vidofludimus as a Farnesoid X Receptor Modulator With Therapeutic Effects on NAFLD. Front Pharmacol. 2020 May 14;11:590. 2. Andreas Muehler, et al. Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2020 Aug;43:102129. 3. Leo R Fitzpatrick, et al. Vidofludimus inhibits colonic interleukin-17 and improves hapten-induced colitis in rats by a unique dual mode of action. J Pharmacol Exp Ther. 2012 Sep;342(3):850-60. |
| 溶解性： |
soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.814 ml |
14.07 ml |
28.141 ml |
| 5 mM |
0.563 ml |
2.814 ml |
5.628 ml |
| 10 mM |
0.281 ml |
1.407 ml |
2.814 ml |
| 50 mM |
0.056 ml |
0.281 ml |
0.563 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
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危險品化學(xué)品經(jīng)營許可證（不帶存儲）
營業(yè)執(zhí)照(三證合一)
北京