Merimepodib
Identification
- Generic Name
- Merimepodib
- DrugBank Accession Number
- DB04862
- Background
Merimepodib (VX-497) is a novel noncompetitive inhibitor of IMPDH. Merimepodib is orally bioavailable and inhibits the proliferation of primary human, mouse, rat, and dog lymphocytes at concentrations of approximately 100 nM.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 452.4599
Monoisotopic: 452.16958452 - Chemical Formula
- C23H24N4O6
- Synonyms
- Merimepodib
- MMPD
- External IDs
- VI-21,497
- VX 497
- VX-497
- VX497
Pharmacology
- Indication
For the treatment of hepatitis C virus (HCV) infection.
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- Pharmacodynamics
Merimepodib, an oral drug, contains a novel inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme responsible for stimulating the production of lymphocytes. Merimepodib has the potential to exert direct antiviral activity, as well as affect the immune response by acting on lymphocyte migration and proliferation. Consequently, merimepodib may be an effective treatment for hepatitis C virus (HCV) infection, as the disease involves both viral proliferation and liver inflammation.
- Mechanism of action
Merimepodib is a orally active inhibitor of inosine monophospate dehydrogenase (IMPDH). IMPDH inhibition leads to a reduction in intracellular guanosine triphosphate (GTP), a molecule required for DNA and RNA synthesis.
Target Actions Organism UInosine-5'-monophosphate dehydrogenase Not Available Streptococcus pyogenes - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenyl-1,3-oxazoles. These are aromatic heterocyclic compounds containing a 1,3-oxazole substituted at one or more positions by a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azoles
- Sub Class
- Oxazoles
- Direct Parent
- Phenyl-1,3-oxazoles
- Alternative Parents
- N-phenylureas / Methoxyanilines / Phenoxy compounds / Anisoles / Methoxybenzenes / Alkyl aryl ethers / Tetrahydrofurans / Carbamate esters / Heteroaromatic compounds / Ureas show 8 more
- Substituents
- Alkyl aryl ether / Anisole / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Dialkyl ether / Ether show 18 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Hepatitis C virus, RSV and other RNA/DNA viruses
Chemical Identifiers
- UNII
- 2ZL2BA06FU
- CAS number
- 198821-22-6
- InChI Key
- JBPUGFODGPKTDW-SFHVURJKSA-N
- 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
- IUPAC Name
- (3S)-oxolan-3-yl N-{[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate
- SMILES
- COC1=C(C=CC(NC(=O)NC2=CC=CC(CNC(=O)O[C@H]3CCOC3)=C2)=C1)C1=CN=CO1
References
- General References
- Markland W, McQuaid TJ, Jain J, Kwong AD: Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon. Antimicrob Agents Chemother. 2000 Apr;44(4):859-66. [Article]
- External Links
- PubChem Compound
- 153241
- PubChem Substance
- 175426871
- ChemSpider
- 135060
- BindingDB
- 50102249
- ChEMBL
- CHEMBL304087
- ZINC
- ZINC000003975663
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Hepatitis / Hepatitis C Virus (HCV) Infection 1 2 Terminated Treatment Coronavirus Disease 2019 (COVID‑19) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.11 mg/mL ALOGPS logP 1.74 ALOGPS logP 1.94 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 11.22 Chemaxon pKa (Strongest Basic) 0.57 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 123.95 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 121.39 m3·mol-1 Chemaxon Polarizability 45.46 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9495 Blood Brain Barrier + 0.8683 Caco-2 permeable - 0.6274 P-glycoprotein substrate Substrate 0.5991 P-glycoprotein inhibitor I Non-inhibitor 0.5808 P-glycoprotein inhibitor II Inhibitor 0.5883 Renal organic cation transporter Non-inhibitor 0.8136 CYP450 2C9 substrate Non-substrate 0.5843 CYP450 2D6 substrate Non-substrate 0.835 CYP450 3A4 substrate Non-substrate 0.5053 CYP450 1A2 substrate Non-inhibitor 0.5894 CYP450 2C9 inhibitor Non-inhibitor 0.5629 CYP450 2D6 inhibitor Non-inhibitor 0.7957 CYP450 2C19 inhibitor Inhibitor 0.5554 CYP450 3A4 inhibitor Inhibitor 0.6474 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7913 Ames test Non AMES toxic 0.5769 Carcinogenicity Non-carcinogens 0.9185 Biodegradation Not ready biodegradable 0.9853 Rat acute toxicity 2.4165 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7275 hERG inhibition (predictor II) Inhibitor 0.6595
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0950100000-218e735786589a55ffb7 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-3891000000-0a627c8e546ba7639ed0 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-016u-0904000000-32c8f7f7f38bf90d9dd9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000l-2900300000-c87a7f5dbc006c4641ea Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0089-1900200000-06e540cba03020bbb1b2 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-066r-3921200000-d290ab76ff3d5fb2776e Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 240.3017814 predictedDarkChem Lite v0.1.0 [M-H]- 205.4782 predictedDeepCCS 1.0 (2019) [M+H]+ 241.8061814 predictedDarkChem Lite v0.1.0 [M+H]+ 207.87375 predictedDeepCCS 1.0 (2019) [M+Na]+ 240.8236814 predictedDarkChem Lite v0.1.0 [M+Na]+ 213.83533 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Streptococcus pyogenes
- Pharmacological action
- Unknown
- General Function
- Metal ion binding
- Specific Function
- Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore pl...
- Gene Name
- guaB
- Uniprot ID
- P0C0H6
- Uniprot Name
- Inosine-5'-monophosphate dehydrogenase
- Molecular Weight
- 52806.77 Da
References
- Jain J, Almquist SJ, Shlyakhter D, Harding MW: VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent. J Pharm Sci. 2001 May;90(5):625-37. [Article]
- Jain J, Almquist SJ, Ford PJ, Shlyakhter D, Wang Y, Nimmesgern E, Germann UA: Regulation of inosine monophosphate dehydrogenase type I and type II isoforms in human lymphocytes. Biochem Pharmacol. 2004 Feb 15;67(4):767-76. [Article]
Drug created at October 19, 2007 21:44 / Updated at February 21, 2021 18:51