Vidofludimus (4sc-101; SC12267) hemicalcium is an orally bioavailable inhibitor of dihydroorotate dehydrogenase (DHODH) and a farnesoid X receptor (FXR) modulator. Vidofludimus hemicalcium works as an immunomodulator and may be utilized to study autoimmune diseases such as inflammatory bowel disease (IBD). Vidofludimus hemicalcium can also be utilized in the research of fatty liver disease by targeting FXR.

Physicochemical Properties

Molecular Formula	C20H18CAFNO4
Molecular Weight	395.437628269196
Exact Mass	748.19
CAS #	1354012-90-0
Related CAS #	Vidofludimus;717824-30-1
PubChem CID	56944639
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	8
Heavy Atom Count	53
Complexity	571
Defined Atom Stereocenter Count	0
InChi Key	KWSJBFAXOPFZSO-UHFFFAOYSA-L
InChi Code	InChI=1S/2C20H18FNO4.Ca/c2*1-26-14-5-2-4-12(10-14)13-8-9-18(17(21)11-13)22-19(23)15-6-3-7-16(15)20(24)25;/h2*2,4-5,8-11H,3,6-7H2,1H3,(H,22,23)(H,24,25);/q;;+2/p-2
Chemical Name	calcium;2-[[2-fluoro-4-(3-methoxyphenyl)phenyl]carbamoyl]cyclopentene-1-carboxylate
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	EC50: 450 nM (FXR)[1] IC50: 160 nM (human DHODH)[3]
ln Vitro	Vidofludimus hemicalcium (0-1 µM) causes the recruitment of several coactivators with LXXLL motifs and selectively activates FXR in a concentration-dependent manner with an EC50 value of roughly 450 nM [1]. The nuclear translocation of p65 is blocked by inhibiting the IKK-IκB-NF-κB pathway with Vidofludimus hemicalcium (0-8 µM) [1]. With an IC50 value of 160 nM, visdofludimus hemicalcium exhibits inhibitory action against human DHODH[2]. In vitro, dihydroorotate dehydrogenase and lymphocyte proliferation are inhibited by visdofludimus hemicalcium [3]. Vidofludimus hemicalcium, regardless of its impact on lymphocyte proliferation, suppresses the release of interleukin (IL)-17 in vitro [3]. In vitro, IL-23 + IL-1β-stimulated colon strips do not produce any IL-17 secretion when vidofludimus hemicalcium is present [3].
ln Vivo	In vivo colitis produced by dextran sulfate sodium (DSS) is impacted by vidofludimus hemicalcium (ip; once daily; for 14 days) in a way that is dependent on FXR [1]. Oral Vidofludimus hemicalcium (60 mg/kg) for 6 days significantly improves several TNBS-induced colitis parameters in rats and inhibits colonic STAT3 and IL-17 [3].
References	[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.
Additional Infomation	Vidofludimus Calcium Anhydrous is the calcium salt form of vidofludimus, 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.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5288 mL	12.6441 mL	25.2883 mL
	5 mM	0.5058 mL	2.5288 mL	5.0577 mL
	10 mM	0.2529 mL	1.2644 mL	2.5288 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.