Farnesoid X Receptor (FXR): Vidofludimus acts as a FXR modulator; in FXR dual-luciferase reporter gene assay (using HEK293T cells transfected with human FXR), the EC50 for FXR activation was approximately 3.2 μM. It also inhibited FXR-mediated transactivation of negative regulatory targets, with an IC50 of ~5.8 μM for suppressing CYP7A1 promoter activity (a FXR-repressed gene) in HepG2 cells [1]
- Dihydroorotate dehydrogenase (DHODH): Vidofludimus calcium (calcium salt form of Vidofludimus) inhibits human DHODH enzyme activity; in purified human DHODH assay, the IC50 was 1.8 nM, and for murine DHODH, the IC50 was 2.5 nM. It showed no significant inhibition on other pyrimidine/purine synthesis enzymes (e.g., thymidylate synthase, inosine monophosphate dehydrogenase) at concentrations up to 10 μM [2]
- Interleukin-17 (IL-17) signaling: Vidofludimus inhibits IL-17 secretion from activated rat splenocytes and human peripheral blood mononuclear cells (PBMCs), with an EC50 of 4.5 μM (rat splenocytes) and 3.9 μM (human PBMCs) [3]

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].

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Hepatocytes (HepG2, primary mouse hepatocytes) for NAFLD:
- FXR target gene regulation: Treatment of HepG2 cells with Vidofludimus (1-20 μM) for 24 h dose-dependently upregulated FXR-activated genes (BSEP, SHP, FGF19) and downregulated FXR-repressed genes (CYP7A1, ACLY). At 10 μM, BSEP mRNA expression increased by 3.8-fold, SHP by 4.2-fold, while CYP7A1 decreased by 0.3-fold (vs. control) [1]
- Lipid accumulation inhibition: Primary mouse hepatocytes were treated with oleic acid (0.2 mM) to induce lipid accumulation, then co-incubated with Vidofludimus (2-15 μM) for 48 h. Oil Red O staining showed that 10 μM Vidofludimus reduced intracellular lipid content by 52% (vs. oleic acid group). Western blot revealed decreased expression of lipogenic proteins (SREBP-1c, FASN) by 0.4-fold and 0.35-fold, respectively [1]
- Immune cells (human CD4⁺ T cells, mouse splenocytes) for RRMS:
- DHODH-mediated pyrimidine synthesis inhibition: Human CD4⁺ T cells activated with anti-CD3/anti-CD28 (5 μg/mL each) were treated with Vidofludimus calcium (0.1-10 nM) for 72 h. The drug dose-dependently reduced intracellular pyrimidine nucleotide (UMP, CTP) levels: 1 nM reduced UMP by 45% and CTP by 38% (vs. activated control). It also inhibited T cell proliferation (CFSE staining): 2 nM reduced proliferation index by 62% [2]
- Pro-inflammatory cytokine suppression: Mouse splenocytes activated with LPS (1 μg/mL) + PMA (10 ng/mL) were treated with Vidofludimus calcium (0.5-5 nM) for 48 h. ELISA showed 2 nM reduced IFN-γ secretion by 55%, TNF-α by 48%, and IL-17A by 52% (vs. activated control) [2]
- Colonic cells (rat colon epithelial cells, human PBMCs) for colitis:
- IL-17 inhibition: Human PBMCs activated with anti-CD3/anti-CD28 (3 μg/mL each) were treated with Vidofludimus (1-10 μM) for 72 h. ELISA demonstrated 5 μM reduced IL-17A secretion by 68%, IL-17F by 62%, and IL-22 by 55% (vs. activated control). Western blot showed decreased phosphorylation of STAT3 (a downstream mediator of IL-17) by 0.4-fold [3]
- Colon epithelial protection: Rat colon epithelial cells (RCECs) treated with TNF-α (10 ng/mL) to induce damage were co-incubated with Vidofludimus (2-8 μM) for 24 h. LDH release assay showed 5 μM reduced cell damage by 42% (vs. TNF-α group). qPCR revealed upregulated tight junction proteins (occludin, ZO-1) by 2.3-fold and 2.1-fold, respectively [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].

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NAFLD mouse model (high-fat diet, HFD-induced):
- Animals: C57BL/6 mice (male, 6-8 weeks old) fed HFD (60% fat) for 12 weeks to induce NAFLD, then randomized into control (HFD + vehicle), Vidofludimus low-dose (10 mg/kg/day), and high-dose (30 mg/kg/day) groups (n=8/group) [1]
- Efficacy outcomes: After 8 weeks of treatment, high-dose Vidofludimus reduced liver triglyceride (TG) content by 58% (from 185 mg/g to 78 mg/g), liver cholesterol by 45% (from 42 mg/g to 23 mg/g), and serum ALT by 42% (from 85 U/L to 49 U/L), AST by 38% (from 72 U/L to 45 U/L) (vs. control). Hematoxylin-eosin (HE) staining showed reduced hepatic steatosis score (from 3.2 to 1.1) [1]
- Mechanism: qPCR of liver tissue showed high-dose Vidofludimus upregulated FXR target genes (BSEP: 3.5-fold, SHP: 4.1-fold) and downregulated lipogenic genes (CYP7A1: 0.3-fold, SREBP-1c: 0.4-fold) [1]
- Experimental Autoimmune Encephalomyelitis (EAE) mouse model (RRMS surrogate):
- Animals: C57BL/6 mice (female, 6-8 weeks old) immunized with MOG₃₅₋₅₅ peptide (200 μg/mouse) + complete Freund’s adjuvant (CFA) to induce EAE, randomized into vehicle, Vidofludimus calcium (0.5 mg/kg/day, 1 mg/kg/day) groups (n=10/group) [2]
- Efficacy outcomes: 1 mg/kg Vidofludimus calcium delayed EAE onset (from day 10 to day 15) and reduced maximum clinical score (from 3.8 to 1.2). Histopathology of spinal cord showed reduced inflammatory cell infiltration (by 65%) and demyelination (by 70%) (vs. vehicle). Flow cytometry of spinal cord mononuclear cells showed decreased CD4⁺ T cells (by 58%), CD8⁺ T cells (by 52%), and macrophages (by 60%) [2]
- Hapten-induced colitis rat model (DNBS-induced):
- Animals: Sprague-Dawley rats (male, 200-220 g) administered DNBS (2,4-dinitrobenzenesulfonic acid, 150 mg/kg) via enema to induce colitis, randomized into vehicle, Vidofludimus (2.5 mg/kg/day, 5 mg/kg/day, oral) groups (n=6/group) [3]
- Efficacy outcomes: 5 mg/kg Vidofludimus improved weight loss (from -18% to -5% vs. baseline), reduced colon damage score (from 4.8 to 1.5), and decreased colon length shortening (from 6.2 cm to 8.8 cm, vs. vehicle). ELISA of colon tissue homogenate showed reduced IL-17A (by 72%), IL-23 (by 65%), and TNF-α (by 58%) [3]

FXR Activation Assay (dual-luciferase reporter gene):
1. Cell transfection: Seed HEK293T cells into 24-well plates (5×10⁴ cells/well) and incubate overnight. Transfect cells with 0.5 μg human FXR expression plasmid, 0.5 μg FXR-responsive luciferase reporter plasmid (containing BSEP promoter), and 0.05 μg Renilla luciferase plasmid (internal control) using transfection reagent.
2. Drug treatment: After 24 h transfection, replace medium with fresh medium containing Vidofludimus (0.1-50 μM) or FXR agonist (positive control, 10 μM GW4064). Incubate for another 24 h.
3. Luciferase activity detection: Lyse cells with passive lysis buffer, transfer 50 μL lysate to 96-well white plates. Add 100 μL firefly luciferase assay reagent, measure luminescence (L1) using a microplate reader. Then add 100 μL Stop & Glo reagent, measure Renilla luciferase luminescence (L2).
4. Data calculation: Relative FXR activity = (L1/L2) of treatment group / (L1/L2) of vehicle group. EC50 is calculated via GraphPad Prism using dose-response curves [1]
- DHODH Enzyme Activity Assay:
1. Reagent preparation: Prepare reaction buffer (50 mM Tris-HCl, pH 8.0, 50 mM KCl, 10 mM MgCl₂, 0.1% BSA). Mix 200 μL reaction buffer with 5 μM dihydroorotate (DHO, substrate), 100 μM coenzyme Q₁₀ (electron acceptor), and purified human DHODH (0.1 μg/well) in 96-well black plates.
2. Drug treatment: Add Vidofludimus calcium (0.01-100 nM) or DHODH inhibitor (positive control, 10 nM leflunomide) to the mixture, incubate at 37℃ for 10 min.
3. Activity detection: Initiate the reaction by adding 50 μL NADH (0.2 mM, coupled to coenzyme Q₁₀ reduction). Monitor the decrease in absorbance at 340 nm (due to NADH oxidation) every 2 min for 30 min using a microplate reader.
4. Data calculation: DHODH activity = (Δabsorbance/min) of treatment group / (Δabsorbance/min) of vehicle group. IC50 is determined via dose-response curve fitting [2]
- IL-17A ELISA Assay (cell supernatant):
1. Sample preparation: Collect supernatants from Vidofludimus-treated or control activated PBMCs, centrifuge at 3,000 × g for 5 min to remove cell debris, store at -80℃.
2. Plate coating: Add 100 μL anti-human IL-17A capture antibody (diluted in coating buffer) to each well of 96-well ELISA plates, incubate overnight at 4℃. Wash plates 3 times with wash buffer (PBS + 0.05% Tween-20).
3. Blocking and sample addition: Add 200 μL blocking buffer (PBS + 1% BSA) to each well, incubate at 37℃ for 1 h. Remove blocking buffer, add 100 μL supernatants (or IL-17A standards, 0-500 pg/mL) to wells, incubate at 37℃ for 2 h. Wash 3 times.
4. Detection: Add 100 μL biotinylated anti-human IL-17A detection antibody, incubate at 37℃ for 1 h. Wash 3 times, add 100 μL streptavidin-HRP conjugate, incubate at 37℃ for 30 min. Wash 5 times, add 100 μL TMB substrate, incubate in dark for 15 min. Stop reaction with 50 μL 2 M H₂SO₄, measure absorbance at 450 nm. Calculate IL-17A concentration via standard curve [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.

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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.

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Hepatocyte Lipid Accumulation Assay (Oil Red O staining):
1. Cell seeding: Seed primary mouse hepatocytes into 24-well plates (2×10⁵ cells/well) in hepatocyte culture medium, incubate overnight at 37℃, 5% CO₂.
2. Lipid induction and drug treatment: Replace medium with medium containing 0.2 mM oleic acid (to induce lipid accumulation) + Vidofludimus (2-15 μM) or vehicle. Incubate for 48 h, replace medium every 24 h.
3. Staining: Aspirate medium, wash cells twice with PBS. Fix cells with 4% paraformaldehyde for 30 min at room temperature. Wash twice with PBS, add 1 mL Oil Red O working solution (0.5% Oil Red O in isopropanol, diluted 3:2 with water) to each well, incubate for 15 min.
4. Quantification: Wash cells 3 times with PBS to remove excess stain. Add 1 mL isopropanol to each well to elute the dye, incubate for 10 min with shaking. Transfer 200 μL eluate to 96-well plates, measure absorbance at 510 nm. Lipid content is expressed as absorbance value relative to vehicle group [1]
- T Cell Proliferation Assay (CFSE staining):
1. Cell isolation: Isolate human CD4⁺ T cells from peripheral blood using CD4⁺ T cell isolation kit, resuspend in RPMI 1640 medium (10% FBS) at 1×10⁶ cells/mL.
2. CFSE labeling: Add CFSE (5 μM final concentration) to cell suspension, incubate at 37℃ for 10 min. Quench reaction with 5 volumes of cold medium, incubate on ice for 5 min. Wash cells twice with medium.
3. Activation and drug treatment: Seed labeled CD4⁺ T cells into 96-well plates (1×10⁵ cells/well), add anti-CD3 (5 μg/mL) + anti-CD28 (5 μg/mL) for activation, and Vidofludimus calcium (0.1-10 nM) or vehicle. Incubate for 72 h.
4. Flow cytometry analysis: Collect cells, wash twice with PBS + 2% FBS. Analyze CFSE fluorescence intensity using flow cytometry (excitation 488 nm, emission 525 nm). Proliferation index is calculated using flow cytometry software, representing the average number of cell divisions [2]
- Colon Epithelial Cell Damage Assay (LDH release):
1. Cell seeding: Seed rat colon epithelial cells (RCECs) into 96-well plates (1×10⁴ cells/well) in DMEM medium (10% FBS), incubate overnight.
2. Damage induction and drug treatment: Replace medium with medium containing 10 ng/mL TNF-α (to induce damage) + Vidofludimus (2-8 μM) or vehicle. Incubate for 24 h.
3. LDH detection: Collect 50 μL supernatant from each well, transfer to a new 96-well plate. Add 50 μL LDH assay reagent (containing NAD⁺, lactate, and tetrazolium salt) to each well, incubate at room temperature for 30 min.
4. Quantification: Measure absorbance at 490 nm. Cell damage rate = [(absorbance of treatment group - absorbance of normal control)/(absorbance of TNF-α group - absorbance of normal control)] × 100% [3]

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.

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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).

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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

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HFD-Induced NAFLD Mouse Model:
1. Animal selection: 6-8 week-old male C57BL/6 mice (n=24), housed under 12 h light/dark cycle, free access to food and water.
2. Model induction: Mice were fed high-fat diet (HFD, 60% fat content) for 12 weeks to establish NAFLD model. Mice with liver TG content >150 mg/g were included.
3. Grouping and treatment: Mice were randomized into 3 groups (n=8/group):
- Vehicle group: Oral gavage of 0.5% carboxymethylcellulose sodium (CMC-Na) once daily.
- Low-dose group: Oral gavage of Vidofludimus 10 mg/kg/day (dissolved in 0.5% CMC-Na, sonicated to dissolve).
- High-dose group: Oral gavage of Vidofludimus 30 mg/kg/day (same solvent).
Treatment duration: 8 weeks; body weight was measured weekly.
4. Sample collection: At the end of treatment, mice were fasted for 12 h, anesthetized with isoflurane. Collect blood via orbital sinus, centrifuge at 3,500 × g for 15 min to separate serum (for ALT/AST detection). Dissect liver, weigh, and divide into three parts: one fixed in 4% paraformaldehyde (for HE staining), one stored at -80℃ (for qPCR/Western blot), one homogenized (for TG/cholesterol detection) [1]
- MOG₃₅₋₅₅-Induced EAE Mouse Model:
1. Animal selection: 6-8 week-old female C57BL/6 mice (n=30), housed under specific pathogen-free (SPF) conditions.
2. EAE induction: Mice were immunized subcutaneously at 4 sites on the back with 200 μg MOG₃₅₋₅₅ peptide emulsified in CFA (containing 4 mg/mL heat-killed Mycobacterium tuberculosis). On day 0 and day 2 post-immunization, intraperitoneally inject 200 ng pertussis toxin.
3. Grouping and treatment: When EAE clinical signs first appeared (day 7-10), mice were randomized into 3 groups (n=10/group):
- Vehicle group: Oral gavage of 0.2% Tween 80 in PBS once daily.
- Low-dose group: Oral gavage of Vidofludimus calcium 0.5 mg/kg/day (dissolved in 0.2% Tween 80/PBS).
- High-dose group: Oral gavage of Vidofludimus calcium 1 mg/kg/day (same solvent).
Treatment duration: 21 days; clinical score was assessed daily (0 = normal, 1 = tail weakness, 2 = hind limb weakness, 3 = hind limb paralysis, 4 = forelimb + hind limb paralysis, 5 = death).
4. Sample collection: On day 28 post-immunization, mice were euthanized. Dissect spinal cord, fix part in 4% paraformaldehyde (for HE/Luxol fast blue staining), and isolate spinal cord mononuclear cells from the rest for flow cytometry [2]
- DNBS-Induced Colitis Rat Model:
1. Animal selection: Male Sprague-Dawley rats (200-220 g, n=24), housed under SPF conditions, acclimated for 1 week before experiment.
2. Colitis induction: Rats were fasted for 24 h, anesthetized with isoflurane. Administer 150 mg/kg DNBS (dissolved in 50% ethanol, 0.2 mL volume) via rectal enema (inserted 8 cm into the colon). Control rats received 0.2 mL 50% ethanol.
3. Grouping and treatment: 24 h post-DNBS administration, rats were randomized into 4 groups (n=6/group):
- Normal control: No DNBS, oral gavage of vehicle (0.5% CMC-Na).
- Colitis vehicle: DNBS + oral gavage of 0.5% CMC-Na.
- Low-dose: DNBS + oral gavage of Vidofludimus 2.5 mg/kg/day.
- High-dose: DNBS + oral gavage of Vidofludimus 5 mg/kg/day.
Treatment duration: 7 days; body weight and stool consistency were recorded daily.
4. Sample collection: On day 8, rats were euthanized. Dissect colon, measure colon length, score colon damage (based on edema, ulceration, inflammation). Collect colon tissue homogenate (for cytokine ELISA) and fix part in 4% paraformaldehyde (for HE staining) [3]

In vitro toxicity: - Hepatocytes: Vidofludimus (concentration up to 30 μM) did not show significant cytotoxicity to primary mouse hepatocytes or HepG2 cells (MTT assay: cell viability >85% vs. control group) [1] - Immune cells: Vidofludimus calcium (concentration up to 50 nM) did not induce apoptosis in resting human CD4⁺ T cells (Annexin V/PI staining: apoptosis rate <5% vs. control group), but specifically inhibited activated T cells [2] - Colon cells: Vidofludimus (concentration up to 20 μM) had no cytotoxicity to RCEC cells (LDH release <10% vs. normal control group) [3] - In vivo toxicity: - NAFLD mice: High dose of Vidofludimus (30 mg/kg/day, for 8 days) The study did not cause significant changes in body weight (32.5 ± 2.1 g vs. 31.8 ± 1.9 g compared to the carrier), serum BUN (15.2 ± 1.8 mg/dL vs. 14.8 ± 1.5 mg/dL), or creatinine (0.8 ± 0.1 mg/dL vs. 0.7 ± 0.1 mg/dL) over the course of the week. No drug-induced necrosis or inflammation was found in liver histopathology [1] - EAE mice: Vedofludimos calcium (1 mg/kg/day for 21 consecutive days) did not cause leukopenia (peripheral blood leukocyte count: 6.8 ± 0.7 ×10⁹/L vs. solvent group 7.1 ± 0.6 ×10⁹/L) or thrombocytopenia (platelet count: 850 ± 50 ×10⁹/L vs. 870 ± 45 ×10⁹/L) [2] - Colitis rats: Vedofludimos (5 mg/kg/day for 7 consecutive days) had no effect on serum ALT (52 ± 6 U/L vs. solvent group 55 ± 7 U/L) or AST (48 ± 5 U/L vs. 50 ± 6 U/L). No gastrointestinal toxicity (e.g., gastric ulcer) was observed [3]

[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 drug belonging to the DMARDs (disease-modifying antirheumatic drugs) class, used to treat autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. It controls the growth of rapidly proliferating cells, especially lymphocytes crucial for immune responses, by highly selectively inhibiting pyrimidine biosynthesis. Vidofludimus is currently undergoing clinical trials (NCT03722576) for the treatment of primary sclerosing cholangitis. Vidofludimus is an orally bioavailable dihydroorotate dehydrogenase (DHODH) inhibitor with potential anti-inflammatory, immunomodulatory, and antiviral activities. After administration, vidofludimus specifically targets, binds to, and blocks DHODH activation. This blocks the fourth enzymatic step in the de novo synthesis of pyrimidines, thereby inhibiting transcriptional elongation, leading to cell cycle arrest, and inducing apoptosis in activated lymphocytes. DHODH inhibition also leads to metabolic stress in activated lymphocytes and inhibits the release of pro-inflammatory cytokines, including interleukin-17 (IL-17A and IL-17F) and interferon-γ (IFN-γ), thereby alleviating inflammation. Furthermore, DHODH inhibition may produce host antiviral activity against a variety of viruses. DHODH is a mitochondrial enzyme that catalyzes the conversion of dihydroorotate (DHO) to orotate and is a key enzyme in the de novo synthesis of pyrimidines. Metabolically highly active and rapidly proliferating lymphocytes and cells infected by various viruses require de novo synthesis of pyrimidines to meet their needs.
See also: Anhydrous vitamin D-dofludimos calcium (note moved to).
Drug Indications
Investigated for the treatment of multiple sclerosis and rheumatoid arthritis.
Mechanism of Action
SC12267 is a novel, selective, orally effective small molecule inhibitor of dihydroorotate dehydrogenase (DHODH) that interferes with cell proliferation by blocking the pyrimidine synthesis pathway. Its mechanism of action is of great significance for the treatment of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Vedofludimox is an immunomodulatory drug with multiple mechanisms of action, including FXR regulation (used to treat metabolic diseases such as non-alcoholic fatty liver disease), DHODH inhibition (used to treat autoimmune diseases such as relapsing-remitting multiple sclerosis), and IL-17 inhibition (used to treat inflammatory bowel diseases such as colitis) [1][2][3] - In non-alcoholic fatty liver disease, vedofludimox regulates bile acid metabolism by activating FXR (upregulating BSEP to promote bile acid excretion) and inhibits lipogenesis (downregulating SREBP-1c/FASN), thereby improving hepatic steatosis, which distinguishes it from non-FXR-targeted lipid-lowering drugs [1] - Vedofludimox calcium is a new generation of DHODH inhibitor with higher selectivity. Compared to first-generation inhibitors such as leflunomide, DHODH (compared to other pyrimidine enzymes) has a stronger inhibitory effect. It can inhibit pro-inflammatory cytokines (IFN-γ, IL-17), making it a potential therapy for relapsing-remitting multiple sclerosis (RRMS) because it targets both T cell proliferation and inflammation [2]. In colitis, vidofludiolimus exerts a “dual mechanism of action”: it directly inhibits IL-17 secretion from Th17 cells and protects the colonic epithelial barrier function (upregulates tight junction proteins), thereby addressing both inflammation and epithelial damage in colitis [3].

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.

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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.

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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.

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