Vidofludimus 是二氢乳清酸脱氢酶 (DHODH) 的抑制剂，也是法尼醇 X 受体 (FXR) 的新型调节剂，具有口服活性。Vidofludimus 作为一种免疫调节剂，可用于研究自身免疫性疾病，如炎症性肠病 (IBD)。Vidofludimus 还可通过靶向 FXR 用于脂肪肝的研究。
| 生物活性 | Vidofludimus is an orally active inhibitor fordihydroorotate dehydrogenase(DHODH)and also is a novel modulator forfarnesoid 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 targetingFXR[1][2][3]. |
| IC50& Target[1][2] | |
体外研究
(In Vitro) | Vidofludimus (0-1 μM) selectively activats FXR in a concentration dependent manner with an EC50value of about 450 nM in inducing the recruitment of various coactivator LXXLL motifs[1].
Vidofludimus (0-8 μM) blocks nuclear translocation of p65 by suppressing IKK-IκB-NF-κB pathway[1].
Vidofludimus has inhibitory activity for human DHODH with an IC50value of 160 nM[2].
Vidofludimus inhibits dihydro-orotate dehydrogenase and lymphocyte proliferation in vitro[3].
Vidofludimus inhibits interleukin (IL)-17 secretion in vitro independently of effects on lymphocyte proliferation[3].
Vidofludimus completely blocks IL-23 + IL-1β-stimulated secretion of IL-17 by colonic strips in ex vivo[3].
Western Blot Analysis[1] | 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[1] | 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. |
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体内研究
(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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 46 mg/mL(129.45 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.8140 mL | 14.0702 mL | 28.1405 mL | | 5 mM | 0.5628 mL | 2.8140 mL | 5.6281 mL | | 10 mM | 0.2814 mL | 1.4070 mL | 2.8140 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (7.04 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (7.04 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (7.04 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (7.04 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (7.04 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.04 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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