merimepodib   Click here for help

GtoPdb Ligand ID: 10741

Synonyms: MMPD | VX-497 | VX497
Compound class: Synthetic organic
Comment: Merimepodib is an orally bioavailable, non-competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) [4]. It has antiviral activity, suppressing replication of Zika virus (ZIKV) [2], hepatitis C virus (HCV), and other emerging viral pathogens [5]. IMPDH inhibition reduces intracellular guanine nucleotide levels, thus limiting RNA and DNA synthesis both for cellular proliferation, and for viral replication inside host cells. Experimental evidence shows that the activity of merimepodib can augment the anti-replicative effects of other antivirals such as ribavirin and T-705 (favipiravir).
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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

merimepodib 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 8
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 123.95
Molecular weight 452.17
XLogP 1.74
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 COc1cc(ccc1c1cnco1)NC(=O)Nc1cccc(c1)CNC(=O)O[C@@H]1COCC1
Isomeric SMILES COc1cc(ccc1c1cnco1)NC(=O)Nc1cccc(c1)CNC(=O)O[C@@H]1COCC1
InChI InChI=1S/C23H24N4O6/c1-30-20-10-17(5-6-19(20)21-12-24-14-32-21)27-22(28)26-16-4-2-3-15(9-16)11-25-23(29)33-18-7-8-31-13-18/h2-6,9-10,12,14,18H,7-8,11,13H2,1H3,(H,25,29)(H2,26,27,28)/t18-/m0/s1
InChI Key JBPUGFODGPKTDW-SFHVURJKSA-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. Dhar TG, Shen Z, Guo J, Liu C, Watterson SH, Gu HH, Pitts WJ, Fleener CA, Rouleau KA, Sherbina NZ et al.. (2002)
Discovery of N-[2-[2-[[3-methoxy-4-(5-oxazolyl)phenyl]amino]-5-oxazolyl]phenyl]-N-methyl-4- morpholineacetamide as a novel and potent inhibitor of inosine monophosphate dehydrogenase with excellent in vivo activity.
J Med Chem, 45 (11): 2127-30. [PMID:12014950]
2. Kamiyama N, Soma R, Hidano S, Watanabe K, Umekita H, Fukuda C, Noguchi K, Gendo Y, Ozaki T, Sonoda A et al.. (2017)
Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice.
Antiviral Res, 146: 1-11. [PMID:28818572]
3. Marcellin P, Horsmans Y, Nevens F, Grange JD, Bronowicki JP, Vetter D, Purdy S, Garg V, Bengtsson L, McNair L et al.. (2007)
Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C.
J Hepatol, 47 (4): 476-83. [PMID:17629590]
4. Sintchak MD, Nimmesgern E. (2000)
The structure of inosine 5'-monophosphate dehydrogenase and the design of novel inhibitors.
Immunopharmacology, 47 (2-3): 163-84. [PMID:10878288]
5. Tong X, Smith J, Bukreyeva N, Koma T, Manning JT, Kalkeri R, Kwong AD, Paessler S. (2018)
Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens.
Antiviral Res, 149: 34-40. [PMID:29126899]