| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Merimepodib targets inosine-5′-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo synthesis of guanine nucleotides. Inhibition of IMPDH leads to a reduction in intracellular guanosine triphosphate (GTP) levels. This depletion of guanine nucleotides inhibits viral replication and has immunomodulatory effects. Its mechanism is non-competitive.
|
|---|---|
| ln Vitro |
Within 48 hours of starting, VX-497's anti-proliferative effects on cells are reversed [1]. With an IC50 range from 6 to 19 μM, VX-497 exhibits moderate antiviral efficacy against Group II viruses, such as HSV-1, parainfluenza-3 virus, BVDV, VEEV, and dengue virus. With an IC50 of 380 nM, a corresponding CC50 of 5.2 μM, and a therapeutic index of 14, VX-497 is 100 times more effective [2].
In vitro, merimepodib is a potent inhibitor of IMPDH. It has antiviral activity against hepatitis C virus (HCV) and a variety of DNA and RNA viruses in vitro. Its activity is characterized by its ability to reduce intracellular GTP levels and inhibit viral replication in cell-based assays. |
| ln Vivo |
Primary IgM antibody responses are dose-dependently inhibited by port VX-497, which has an ED50 value of about 30-35 mg/kg in mice. It was found that a single daily dose of variable VX-497 was just as effective as twice daily dosing in this immune activation paradigm [1]. Allogeneic F1 mice given a vehicle treatment develop GVHD, and VX-497 treatment greatly reduces all illness symptoms. In animals treated with VX-497, the 2.9-fold rise in kidney weight observed in transplanted mice was lowered to a 1.6-fold increase. The native group's serum IFN-γ levels jumped 54-fold, whereas the VX-497-treated animals' levels increased 7.4-fold [3].
In vivo, merimepodib is an orally active inhibitor of IMPDH. It has been investigated for the treatment of hepatitis C virus (HCV) infection. It holds promise for both infectious disease and oncology applications, especially when combined with other therapeutic strategies. Its in vivo efficacy is dose-dependent and related to its antiviral and immunomodulatory effects. |
| Enzyme Assay |
In vitro enzyme/receptor binding studies for merimepodib typically involve IMPDH inhibition assays. Standard protocols use recombinant IMPDH enzyme incubated with inosine monophosphate (IMP) and NAD in the presence of increasing concentrations of merimepodib. Enzyme activity is measured spectrophotometrically by monitoring the reduction of NAD, and IC₅₀ values are calculated.
|
| Cell Assay |
In vitro cellular assays for merimepodib involve culturing HCV-infected cells or other cell lines in the presence of serial dilutions of the compound. Intracellular GTP levels are measured by HPLC or LC-MS/MS. Viral replication is assessed by measuring viral RNA or protein levels. Cell viability is assessed using standard assays.
|
| Animal Protocol |
In vivo animal studies for merimepodib include models of HCV infection, such as chimeric mice with humanized livers. Animals are treated with merimepodib via oral administration. Endpoints include viral load, liver enzyme levels, and histopathology. Its immunomodulatory effects may be assessed in models of autoimmune diseases or transplantation.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of merimepodib include a molecular weight of 452.46 and a molecular formula of C₂₃H₂₄N₄O₆. It is orally bioavailable. Its CAS name is [[3-[[[[3-Methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]phenyl]methyl] carbamic acid (3S)-tetrahydro-3-furanyl ester. Detailed pharmacokinetic parameters are available from clinical studies.
|
| Toxicity/Toxicokinetics |
Toxicological data for merimepodib are derived from preclinical and clinical studies. As an IMPDH inhibitor, it may affect lymphocyte proliferation and immune function. Common side effects may include gastrointestinal upset, fatigue, and headache. It may cause myelosuppression at higher doses. It is contraindicated in patients with severe immunodeficiency or bone marrow suppression.
|
| References |
|
| Additional Infomation |
Merimepodib (VX-497) is a novel, non-competitive IMPDH inhibitor. Merimepodib has oral bioavailability and inhibits the proliferation of primary human, mouse, rat, and canine lymphocytes at concentrations of approximately 100 nM. Merimepodib is an inosine monophosphate dehydrogenase (IMPDH) inhibitor with activity against hepatitis C virus (HCV). IMPDH catalyzes the rate-limiting step in the de novo synthesis of guanine nucleotides; Merimepodib treatment reduces intracellular guanine nucleotide levels required for RNA and DNA synthesis, thereby producing antiproliferative and antiviral effects. Indications: For the treatment of hepatitis C virus (HCV) infection. Mechanism of Action: Merimepodib is an orally potent inosine monophosphate dehydrogenase (IMPDH) inhibitor. IMPDH inhibition reduces intracellular guanosine triphosphate (GTP) levels; GTP is an essential molecule for DNA and RNA synthesis.
Pharmacodynamics The oral medication Merimepodib contains a novel inosine monophosphate dehydrogenase (IMPDH) inhibitor, an enzyme responsible for stimulating lymphocyte production. Merimepodib has the potential for direct antiviral activity and can influence the immune response by affecting lymphocyte migration and proliferation. Therefore, since hepatitis C virus (HCV) infection involves viral replication and liver inflammation, Merimepodib may be an effective treatment for HCV infection. Merimepodib (VX-497, MMPD) is a potent inhibitor of IMPDH with antiviral and immunomodulatory activity. It was investigated for the treatment of hepatitis C virus (HCV) infection. It has also been studied for its potential in oncology. It is not approved for human therapeutic use and is available for research purposes. |
| Molecular Formula |
C23H24N4O6
|
|---|---|
| Molecular Weight |
452.46
|
| Exact Mass |
452.169
|
| Elemental Analysis |
C, 61.05; H, 5.35; N, 12.38; O, 21.22
|
| CAS # |
198821-22-6
|
| Related CAS # |
(R)-Merimepodib
|
| PubChem CID |
153241
|
| Appearance |
white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
571.4±50.0 °C at 760 mmHg
|
| Flash Point |
299.4±30.1 °C
|
| Vapour Pressure |
0.0±1.6 mmHg at 25°C
|
| Index of Refraction |
1.632
|
| LogP |
2.05
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
33
|
| Complexity |
652
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O1C([H])([H])C([H])([H])[C@@]([H])(C1([H])[H])OC(N([H])C([H])([H])C1C([H])=C([H])C([H])=C(C=1[H])N([H])C(N([H])C1C([H])=C([H])C(C2=C([H])N=C([H])O2)=C(C=1[H])OC([H])([H])[H])=O)=O
|
| InChi Key |
BPUGFODGPKTDW-SFHVURJKSA-N
|
| InChi Code |
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
|
| Chemical Name |
(S)-tetrahydrofuran-3-yl 3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate
|
| Synonyms |
Merimepodib; VX497; VX-497; VX 497; MMP; VI21497; VI-21497; VI 21497
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 31~90 mg/mL (68.51~198.91 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.53 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (5.53 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2101 mL | 11.0507 mL | 22.1014 mL | |
| 5 mM | 0.4420 mL | 2.2101 mL | 4.4203 mL | |
| 10 mM | 0.2210 mL | 1.1051 mL | 2.2101 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
