Vidofludimus (0-1 µM) selectively activates FXR in a concentration-dependent manner, with an EC50 value of approximately 450 nM, inducing the recruitment of various coactivator LXXLL motifs [1]. Vidofludimus (0-8 µM) inhibits nuclear translocation of p65 by suppressing the IKK-IκB-NF-κB pathway [1]. Vidofludimus inhibits human DHODH with an IC50 of 160 nM [2]. Vidofludimus inhibits dihydroorotate dehydrogenase and lymphocyte proliferation in vitro[3]. Vidofludimus inhibits interleukin (IL)-17 secretion in vitro, regardless of the effects on lymphocyte proliferation [3]. Vidofludimus completely inhibits IL-23 + IL-1β-stimulated IL-17 secretion by colonic strips in ex vivo[3].

In vivo, vidofludimus (ip; once daily; for 14 days) affects colitis produced by dextran sodium sulfate (DSS) in a way that is dependent on FXR[1]. Vidofludimus (po; 60 mg/kg; for 6 days) inhibits colonic STAT3 and IL-17 and successfully improves numerous parameters of TNBS-induced colitis in rats[3].

Western Blot Analysis[1]
Cell Types: HepG2 cells or MEFs
Tested Concentrations: 2, 8 μM
Incubation Duration: 1 h
Experimental Results: Inhibited of TNFα-induced IKKα/β phosphorylation and IκBα degradation.

---

RT-PCR[1]
Cell Types: HepG2 cells
Tested Concentrations: 5 μM
Incubation Duration: 24 h
Experimental Results: Inhibited the increase of NF-κB target genes MCP-1 and CXCL-2 upon TNFα stimulation.

Animal/Disease Models: homozygous FXR deficient (FXR KO) mice[1] (10weeks old, male)
Doses: 20 mg /kg
Route of Administration: po (oral gavage) 20 mg/kg/day
Experimental Results: Revealed multifocal inflammatory cell infiltration and edema with crypt and epithelial cell destruction and ulceration.

---

Animal/Disease Models: NAFLD Model[1] (10-11 weeks old male obese Lepob/ob C57BL /6 (ob/ob) mice)
Doses: 10 mg/kg
Route of Administration: intraperitoneally, one time/day, for 14 days
Experimental Results: Dramatically decreased body weight loss, prevented colonic shortening, diminished histological scores, and disease activity index (DAI) scores in WT mice. Dramatically diminished colonic mRNA expression of the pro-inflammatorygenes interleukin (IL)-1β, IL-6, IL-17, and prostaglandin-endoperoxide synthase 2 (COX-2).

---

Animal/Disease Models: Wistar rats[3]
Doses: 60 mg/kg
Route of Administration: po, for 6 days
Experimental Results: Effectively decreased macroscopic and histological pathology and the numbers of CD3+ T cells in vivo. decreased nuclear signal transducer and activator of transcription 3 (ST

[1]. Repositioning an Immunomodulatory Drug Vidofludimus as a Farnesoid X Receptor Modulator With Therapeutic Effects on NAFLD. Front Pharmacol. 2020 May 14;11:590.

[2]. Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2020 Aug;43:102129.

[3]. 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.

SC12267 is a novel, small molecule agent from the class of DMARDs (disease modifying anti-rheumatic drug) for the therapy of autoimmune diseases such as rheumatoid arthritis or multiple sclerosis. Through highly selective inhibition of pyrimidine biosynthesis, it controls the growth of rapidly proliferating cells, especially of lymphocytes, which are important for the immune response.
Vidofludimus is under investigation in clinical trial NCT03722576 (Vidofludimus Calcium for Primary Sclerosing Cholangitis).
Vidofludimus is an orally bioavailable inhibitor of dihydroorotate dehydrogenase (DHODH), with potential anti-inflammatory, immunomodulating and anti-viral activities. Upon administration, vidofludimus specifically targets, binds to and prevents the activation of DHODH. This prevents the fourth enzymatic step in de novo pyrimidine synthesis, leading to inhibition of transcriptional elongation, cell cycle arrest, and apoptosis in activated lymphocytes. DHODH inhibition also leads to metabolic stress in activated lymphocytes and inhibition of the release of proinflammatory cytokines including interleukin (IL)-17 (IL-17A and IL-17F) and interferon-gamma (IFNg), thereby reducing inflammation. In addition, DHODH inhibition may lead to host-based anti-viral activity against many viruses. DHODH, a mitochondrial enzyme that catalyzes the conversion of dihydroorotate (DHO) to orotate, is a key enzyme in pyrimidine de novo biosynthesis. Metabolically highly activated and rapidly proliferating lymphocytes and various virus infected cells require de novo synthesis to meet their needs for pyrimidines.
See also: vidofludimus calcium anhydrous (annotation moved to).

---

Drug Indication
Investigated for use/treatment in multiple sclerosis and rheumatoid arthritis.

---

Mechanism of Action
SC12267, a novel, selective and orally available, small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), interferes with cell proliferation through blocking the synthesis pathway of pyrimidines. Its mode-of- action is of therapeutic relevance for the treatment of autoimmune disorders such as rheumatoid arthritis and multiple sclerosis.

C20H18FNO4

355.36

355.121

717824-30-1

Vidofludimus hemicalcium;1354012-90-0

9820008

Light yellow to gray solid powder

1.4±0.1 g/cm3

567.5±50.0 °C at 760 mmHg

297.0±30.1 °C

0.0±1.6 mmHg at 25°C

1.634

4.22

2

5

5

26

576

0

XPRDUGXOWVXZLL-UHFFFAOYSA-N

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)

2-[[2-fluoro-4-(3-methoxyphenyl)phenyl]carbamoyl]cyclopentene-1-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 2.5 mg/mL (7.04 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: 2.5 mg/mL (7.04 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (7.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)