NAV

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
3D
Similar Structures
Weight
Average: 452.4599
Monoisotopic: 452.16958452
Chemical Formula
C23H24N4O6
Synonyms
  • Merimepodib
  • MMPD
External IDs
  • VI-21,497
  • VX 497
  • VX-497
  • VX497
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Pharmacology

Indication

For the treatment of hepatitis C virus (HCV) infection.

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Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
UInosine-5'-monophosphate dehydrogenaseNot AvailableStreptococcus 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
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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
  1. 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]
PubChem Compound
153241
PubChem Substance
175426871
ChemSpider
135060
BindingDB
50102249
ChEMBL
CHEMBL304087
ZINC
ZINC000003975663

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHepatitis / Hepatitis C Virus (HCV) Infection1
2TerminatedTreatmentCoronavirus 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
PropertyValueSource
Water Solubility0.11 mg/mLALOGPS
logP1.74ALOGPS
logP1.94Chemaxon
logS-3.6ALOGPS
pKa (Strongest Acidic)11.22Chemaxon
pKa (Strongest Basic)0.57Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area123.95 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity121.39 m3·mol-1Chemaxon
Polarizability45.46 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9495
Blood Brain Barrier+0.8683
Caco-2 permeable-0.6274
P-glycoprotein substrateSubstrate0.5991
P-glycoprotein inhibitor INon-inhibitor0.5808
P-glycoprotein inhibitor IIInhibitor0.5883
Renal organic cation transporterNon-inhibitor0.8136
CYP450 2C9 substrateNon-substrate0.5843
CYP450 2D6 substrateNon-substrate0.835
CYP450 3A4 substrateNon-substrate0.5053
CYP450 1A2 substrateNon-inhibitor0.5894
CYP450 2C9 inhibitorNon-inhibitor0.5629
CYP450 2D6 inhibitorNon-inhibitor0.7957
CYP450 2C19 inhibitorInhibitor0.5554
CYP450 3A4 inhibitorInhibitor0.6474
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7913
Ames testNon AMES toxic0.5769
CarcinogenicityNon-carcinogens0.9185
BiodegradationNot ready biodegradable0.9853
Rat acute toxicity2.4165 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7275
hERG inhibition (predictor II)Inhibitor0.6595
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0950100000-218e735786589a55ffb7
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-3891000000-0a627c8e546ba7639ed0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-016u-0904000000-32c8f7f7f38bf90d9dd9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000l-2900300000-c87a7f5dbc006c4641ea
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0089-1900200000-06e540cba03020bbb1b2
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-066r-3921200000-d290ab76ff3d5fb2776e
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-240.3017814
predicted
DarkChem Lite v0.1.0
[M-H]-205.4782
predicted
DeepCCS 1.0 (2019)
[M+H]+241.8061814
predicted
DarkChem Lite v0.1.0
[M+H]+207.87375
predicted
DeepCCS 1.0 (2019)
[M+Na]+240.8236814
predicted
DarkChem Lite v0.1.0
[M+Na]+213.83533
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Inosine-5'-monophosphate dehydrogenase
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
  1. 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]
  2. 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