vidofludimus   Click here for help

GtoPdb Ligand ID: 9860

Synonyms: 4SC-101 | IMU-838 (vidofludimus calcium) | SC12267
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Vidofludimus (4SC-101) is a small molecule dihydroorotate dehydrogenase (DHOD) inhibitor that was developed for immunosuppressive potential [3]. It has an improved toxicity profile in comparison to the clinically used disease modifying anti-rheumatic drug (DMARD) leflunomide.
Since its initial development, vidofludimus has been superceded by IMU-838 which is an orally active polymorph of vidofludimus calcium (PubChem CID: 56944639) [5].SARS-CoV-2 and COVID-19: The target of vidofludimus, DHODH, plays a role in the metabolism of activated T cells and B cells to regulate the inflammatory response. It has been advanced to clinical trial in patients with severe COVID-19, to as attempt to block the release of pro-inflammatory cytokines and temper hyperinflammation in these patients.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

vidofludimus is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 75.63
Molecular weight 355.12
XLogP 3.34
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1cccc(c1)c1ccc(c(c1)F)NC(=O)C1=C(CCC1)C(=O)O
Isomeric SMILES COc1cccc(c1)c1ccc(c(c1)F)NC(=O)C1=C(CCC1)C(=O)O
InChI 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)
InChI Key XPRDUGXOWVXZLL-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Fitzpatrick LR, Deml L, Hofmann C, Small JS, Groeppel M, Hamm S, Lemstra S, Leban J, Ammendola A. (2010)
4SC-101, a novel immunosuppressive drug, inhibits IL-17 and attenuates colitis in two murine models of inflammatory bowel disease.
Inflamm Bowel Dis, 16 (10): 1763-77. [PMID:20310011]
2. Herrlinger KR, Diculescu M, Fellermann K, Hartmann H, Howaldt S, Nikolov R, Petrov A, Reindl W, Otte JM, Stoynov S et al.. (2013)
Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study.
J Crohns Colitis, 7 (8): 636-43. [PMID:23078909]
3. Kulkarni OP, Sayyed SG, Kantner C, Ryu M, Schnurr M, Sárdy M, Leban J, Jankowsky R, Ammendola A, Doblhofer R et al.. (2010)
4SC-101, a novel small molecule dihydroorotate dehydrogenase inhibitor, suppresses systemic lupus erythematosus in MRL-(Fas)lpr mice.
Am J Pathol, 176 (6): 2840-7. [PMID:20413687]
4. Leban J, Vitt D. (2011)
Human dihydroorotate dehydrogenase inhibitors, a novel approach for the treatment of autoimmune and inflammatory diseases.
Arzneimittelforschung, 61 (1): 66-72. [PMID:21355448]
5. Muehler A, Kohlhof H, Groeppel M, Vitt D. (2020)
Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single and Multiple Ascending Oral Doses in Healthy Male Subjects.
Eur J Drug Metab Pharmacokinet, 45 (5): 557-573. [PMID:32361977]
6. Muehler A, Peelen E, Kohlhof H, Gröppel M, Vitt D. (2020)
Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis.
Mult Scler Relat Disord, 43: 102129. [PMID:32428844]
7. Vietor J, Gege C, Stiller T, Busch R, Schallmayer E, Kohlhof H, Höfner G, Pabel J, Marschner JA, Merk D. (2023)
Development of a Potent Nurr1 Agonist Tool for In Vivo Applications.
J Med Chem,. DOI: 10.1021/acs.jmedchem.3c00415