WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 510319
CAS#: 717824-30-1 (free acid)
Description: Vidofludimus, also known as 4SC 101 or SC12267, is a novel orally active and potent DHODH inhibitor. In vitro, 4SC-101 is a potent inhibitor of human DHODH, inhibits lymphocyte proliferation, and uniquely blocks phytohemagglutinin-stimulated IL-17 production by lymphocytes. In vivo, oral administration of 4SC-101 effectively improved both chronic DSS and acute TNBS colitis in mice. 4SC-101 may have potential for the treatment of intestinal inflammation. Dihydroorotate dehydrogenase (DHODH) is a key enzyme involved in pyrimidine biosynthesis. DHODH is a known target for the treatment of autoimmune diseases.
MedKoo Cat#: 510319
Name: Vidofludimus
CAS#: 717824-30-1 (free acid)
Chemical Formula: C20H18FNO4
Exact Mass: 355.122
Molecular Weight: 355.36
Elemental Analysis: C, 67.60; H, 5.11; F, 5.35; N, 3.94; O, 18.01
Related CAS #: 717824-30-1 (free acid) 1354012-90-0 (Calium) 1354013-27-6 (potassium) 2245772-26-1 (sodium) 1354023-23-6 (tris)
Synonym: Vidofludimus; 4SC 101; 4SC-101; 4SC101; SC12267; SC-12267; SC 12267; IMU-838; IMU838; IMU 838; IM90838; IM 90838; IM-90838;
IUPAC/Chemical Name: 2-((3-fluoro-3'-methoxy-[1,1'-biphenyl]-4-yl)carbamoyl)cyclopent-1-enecarboxylic acid
InChi Key: XPRDUGXOWVXZLL-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: COC1=CC=CC(C2=CC(F)=C(NC(C3=C(C(O)=O)CCC3)=O)C=C2)=C1
Appearance: Light yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Vidofludimus(4SC-101; SC12267) is a novel immunosuppressive drug that inhibits DHODH and inhibits IL-17 in vitro. |
| In vitro activity: | The antiviral activity of IMU-838 was determined by RT-qPCR using infectious supernatants of SARS-CoV-2-infected Vero cells. Cells were used for infection with SARS-CoV-2 at an MOI of 0.0002 for 2–3 days, before supernatants were collected and subjected to the determination of extracellular viral load by RT-qPCR. In all cases of the slightly modified settings in replicates 1–3, the EC50 values of IMU-838 remained in the low micromolar range (6.0 ± 5.0 µM to 10.0 ± 9.0 µM), so that a mean of 7.6 ± 5.8 µM was calculated (Figure 3A). This result was further illustrated by the use of the remaining cell layers for assessing the drug-mediated inhibition of intracellular viral load by an immunostaining of cell layers in the in-cell ELISA (Figure 3B). This finding was supported by the in-cell IF data described above, indicating the IMU-838-mediated inhibition of viral spike protein and RNA production, with a concentration-dependent reduction of both signals, as compared to the DMSO infection-positive and mock-infected negative controls (Figure 1C). These data indicated a pronounced in vitro anti-SARS-CoV-2 activity of the developmental drug IMU-838. Reference: Viruses. 2020 Dec; 12(12): 1394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762174/ |
| In vivo activity: | Female MRl lpr/lpr mice were treated with 4SC-101, CYC, or vehicle from 12 to 22 weeks of age because at 12 weeks of age MRLlpr/lpr mice show first signs of proliferative immune complex glomerulonephritis and proteinuria. After 10 weeks of treatment, vehicle-treated MRLlpr/lpr mice showed diffuse proliferative immune complex glomerulonephritis characterized by glomerular IgG deposits, mesangioproliferative glomerulonephritis, considerable tubular atrophy, and interstitial fibrosis (Figure 4A). 4SC-101 reduced the glomerular IgG deposits and improved the lupus-like immune complex glomerulonephritis in female MRLlpr/lpr mice in a dose dependent manner (Figure 4A). The chronicity score, a composite score of glomerular and interstitial scarring, was significant for the 300 mg/kg 4SC-101 group. 300 mg/kg 4SC-101 reduced renal macrophage and T cell infiltrates (Figure 4C). 4SC-101 treatment was also associated with an increase of GFR (Glomerular filtration rate) and a decrease of albuminuria in a dose-dependent manner (Figure 5, A and B). It is concluded that the dose-dependent impact of 4SC-101 on systemic autoimmunity translates into antiinflammatory effects on lupus nephritis and improvement of renal dysfunction in MRLlpr/lpr mice. Reference: Am J Pathol. 2010 Jun; 176(6): 2840–2847. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877845/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 57.0 | 160.4 |
The following data is based on the product molecular weight 355.36 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Kulkarni OP, Sayyed SG, Kantner C, Ryu M, Schnurr M, Sárdy M, Leban J, Jankowsky R, Ammendola A, Doblhofer R, Anders HJ. 4SC-101, a novel small molecule dihydroorotate dehydrogenase inhibitor, suppresses systemic lupus erythematosus in MRL(Fas)lpr mice. Am J Pathol. 2010 Jun;176(6):2840-7. doi: 10.2353/ajpath.2010.091227. Epub 2010 Apr 22. PMID: 20413687; PMCID: PMC2877845. 2. Hahn F, Wangen C, Häge S, Peter AS, Dobler G, Hurst B, Julander J, Fuchs J, Ruzsics Z, Überla K, Jäck HM, Ptak R, Muehler A, Gröppel M, Vitt D, Peelen E, Kohlhof H, Marschall M. IMU-838, a Developmental DHODH Inhibitor in Phase II for Autoimmune Disease, Shows Anti-SARS-CoV-2 and Broad-Spectrum Antiviral Efficacy In Vitro. Viruses. 2020 Dec 5;12(12):1394. doi: 10.3390/v12121394. PMID: 33291455; PMCID: PMC7762174. |
| In vitro protocol: | 1. Kulkarni OP, Sayyed SG, Kantner C, Ryu M, Schnurr M, Sárdy M, Leban J, Jankowsky R, Ammendola A, Doblhofer R, Anders HJ. 4SC-101, a novel small molecule dihydroorotate dehydrogenase inhibitor, suppresses systemic lupus erythematosus in MRL(Fas)lpr mice. Am J Pathol. 2010 Jun;176(6):2840-7. doi: 10.2353/ajpath.2010.091227. Epub 2010 Apr 22. PMID: 20413687; PMCID: PMC2877845. 2. Hahn F, Wangen C, Häge S, Peter AS, Dobler G, Hurst B, Julander J, Fuchs J, Ruzsics Z, Überla K, Jäck HM, Ptak R, Muehler A, Gröppel M, Vitt D, Peelen E, Kohlhof H, Marschall M. IMU-838, a Developmental DHODH Inhibitor in Phase II for Autoimmune Disease, Shows Anti-SARS-CoV-2 and Broad-Spectrum Antiviral Efficacy In Vitro. Viruses. 2020 Dec 5;12(12):1394. doi: 10.3390/v12121394. PMID: 33291455; PMCID: PMC7762174. |
| In vivo protocol: | 1. Kulkarni OP, Sayyed SG, Kantner C, Ryu M, Schnurr M, Sárdy M, Leban J, Jankowsky R, Ammendola A, Doblhofer R, Anders HJ. 4SC-101, a novel small molecule dihydroorotate dehydrogenase inhibitor, suppresses systemic lupus erythematosus in MRL(Fas)lpr mice. Am J Pathol. 2010 Jun;176(6):2840-7. doi: 10.2353/ajpath.2010.091227. Epub 2010 Apr 22. PMID: 20413687; PMCID: PMC2877845 |
1: Fitzpatrick LR. Inhibition of IL-17 as a pharmacological approach for IBD. Int Rev Immunol. 2013 Oct-Dec;32(5-6):544-55. doi: 10.3109/08830185.2013.821118. Epub 2013 Jul 25. Review. PubMed PMID: 23886112.
2: Herrlinger KR, Diculescu M, Fellermann K, Hartmann H, Howaldt S, Nikolov R, Petrov A, Reindl W, Otte JM, Stoynov S, Strauch U, Sturm A, Voiosu R, Ammendola A, Dietrich B, Hentsch B, Stange EF. Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study. J Crohns Colitis. 2013 Sep 1;7(8):636-43. doi: 10.1016/j.crohns.2012.09.016. Epub 2012 Oct 16. PubMed PMID: 23078909.
3: Fitzpatrick LR, Small JS, Doblhofer R, Ammendola A. 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. doi: 10.1124/jpet.112.192203. Epub 2012 Jun 12. PubMed PMID: 22691298.
4: Rusai K, Schmaderer C, Baumann M, Chmielewski S, Prókai A, Kis E, Szabó AJ, Leban J, Doblhofer R, Ammendola A, Lutz J, Heemann U. Immunosuppression with 4SC-101, a novel inhibitor of dihydroorotate dehydrogenase, in a rat model of renal transplantation. Transplantation. 2012 Jun 15;93(11):1101-7. doi: 10.1097/TP.0b013e31824fd861. PubMed PMID: 22609757.
5: Fitzpatrick LR. Novel Pharmacological Approaches for Inflammatory Bowel Disease: Targeting Key Intracellular Pathways and the IL-23/IL-17 Axis. Int J Inflam. 2012;2012:389404. doi: 10.1155/2012/389404. Epub 2012 Mar 15. PubMed PMID: 22506136; PubMed Central PMCID: PMC3312283.
6: New preclinical findings with vidofludimus. Immunotherapy. 2010 Jul;2(4):439. PubMed PMID: 20648986.
7: Fitzpatrick LR, Deml L, Hofmann C, Small JS, Groeppel M, Hamm S, Lemstra S, Leban J, Ammendola A. 4SC-101, a novel immunosuppressive drug, inhibits IL-17 and attenuates colitis in two murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2010 Oct;16(10):1763-77. doi: 10.1002/ibd.21264. PubMed PMID: 20310011.
