Merimepodib

HCID 153241

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Basic information

CAS: 198821-22-6
Standard SMILES: COc1cc(NC(=O)Nc2cccc(CNC(=O)O[C@H]3CCOC3)c2)ccc1-c1cnco1
InChIKey: JBPUGFODGPKTDW-SFHVURJKSA-N
Molecular formula: C23H24N4O6
Average molar mass: 452.5 g/mol
Monoisotopic mass: 452.16958449

Overview

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.

Names & identifiers

Preferred name: Merimepodib
IUPAC: [(3S)-oxolan-3-yl] N-[[3-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoylamino]phenyl]methyl]carbamate
English name: MeriMepodib, VI-21497, VX-497
Molecular formula: C23H24N4O6
Molecular weight: 452.46

Names & synonyms

Merimepodib198821-22-6VX-497MMPD2ZL2BA06FUVI-21497VI-21,497DTXSID70173639Carbamic acid, ((3-((((3-methoxy-4-(5-oxazolyl)phenyl)amino)carbonyl)amino)phenyl)methyl)-, (3S)-tetrahydro-3-furanyl ester(3S)-oxolan-3-yl N-{[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate(3S)-oxolan-3-yl N-((3-(((3-methoxy-4-(1,3-oxazol-5-yl)phenyl)carbamoyl)amino)phenyl)methyl)carbamatecarbamic acid, [[3-[[[[3-methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]phenyl]methyl]-, (3S)-tetrahydro-3-furanyl ester

Show more names

VI 21497Merimepodib (VX-497)Merimepodib (VI-21497Merimepodib, 10 mM in DMSOMeriMepodib, VI-21497, VX-497VX497VX 497MMPVI21497VI 21497HCV,Inhibitor,Merimepodib,HBV,Hepatitis C virus,Hepatitis B virus,VX497,VX 497,inhibit,MMPD[[3-[[[[3-Methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]phenyl]methyl]carbamic acid (3S)-tetrahydro-3-furanyl ester

MERIMEPODIBUMRefChem:811132DTXCID6096130(S)-tetrahydrofuran-3-yl 3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate[(3S)-oxolan-3-yl] N-[[3-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoylamino]phenyl]methyl]carbamateMFCD09837807Carbamic acid, N-[[3-[[[[3-methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]phenyl]methyl]-, (3S)-tetrahydro-3-furanyl esterCHEMBL304087

Database identifiers

CAS: 198821-22-6
PubChem CID: 153241
DTXSID: DTXSID70173639
ChEMBL: CHEMBL304087
UNII: 2ZL2BA06FU
Nikkaji: J1.291.375C

Properties

Computed structural properties

XLogP: 2.1
Topological polar surface area: 124 Å²
Hydrogen bond donors: 3
Hydrogen bond acceptors: 7
Rotatable bonds: 8
Heavy atoms: 33
Formal charge: 0
Complexity: 652

Experimental & physicochemical properties

DrugsPharmaceuticals -> Listed in ZINC15

LogP3.6

Physicochemical properties

Boiling point: 571.4 · 571.4±50.0 °C(Predicted)
Density: 1.36 · 1.36±0.1 g/cm3(Predicted)
storage temp.: Sealed in dry,Room Temperature
solubility: 45.2 mg/mL · ≥45.2 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
form: solid
pka: 11.66 · 11.66±0.46(Predicted)
color: Off-white to light yellow
FDA UNII: 2 ZL2BA06FU · 2ZL2BA06FU
Symbol(GHS): 7 · GHS07
Signal word: Warning
Hazard statements: 302 · H302-H315-H319
Precautionary statements: 501 · P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Safety & regulation

Safety data

Signal word: Warning
Symbol(GHS): GHS07
Hazard statements: H302-H315-H319
Precautionary statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Chemistry & industry

Pharmacology

Pharmacodynamics · 1 item

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 ActionMerimepodib 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.

Applications · 2 items

DescriptionMerimepodib is an inhibitor of inosine-5''-monophosphate dehydrogenase (IMPDH; Kis = 7 and 10 nM for IMPDH type I and type II, respectively) with antiviral and immunosuppressant activities. It reduces Ebola, Lassa, chikungunya, Junin, and Zika virus titers in vitro and inhibits Zika virus replication in Huh7 cells (EC50 = 0.6 μM). Merimepodib inhibits the proliferation of PHA-stimulated T cells and SPAS-stimulated B cells (IC50s = 104 and 132 nM, respectively), effects that can be reversed by guanosine but not adenosine . In vivo, merimepodib (50 and 100 mg/kg) increases allograft survival in a murine skin transplantation model and prevents development of graft versus host disease (GVHD) in splenocyte allografted mice.

UsesInhibition of inosine monophosphate dehydrogenase (IMPDH), which has potential antiviral, antiproliferative, antiparasitic, and immunosuppressive activity.