Synonym
Merimepodib; VX497; VX-497; VX 497; MMP; VI21497; VI-21497; VI 21497.
IUPAC/Chemical Name
(S)-tetrahydrofuran-3-yl 3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate
InChi Key
JBPUGFODGPKTDW-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
SMILES Code
O=C(O[C@@H]1COCC1)NCC2=CC=CC(NC(NC3=CC=C(C4=CN=CO4)C(OC)=C3)=O)=C2
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Merimepodib (VX-497) is a noncompetitive and oral inhibitor of inosine monophosphate dehydrogenase (IMPDH) with broad spectrum antiviral activities.
In vitro activity:
VX-497 is most potent against the first group of viruses, which includes HBV, HCMV, EMCV, and RSV, with 50% inhibitory concentrations (IC50s) of 0.38, 0.80, 1.0, and 1.14 μM, respectively. VX-497 has intermediate antiviral activity against a second group of viruses, which includes HSV-1, parainfluenza-3 virus, BVDV, VEEV, and dengue virus, with IC50s ranging from 6 to 19 μM. VX497 did not demonstrate antiviral efficacy against the third group of viruses, as measured by its inability to achieve an IC50 measurement for YFV, coxsackie B3 virus, or influenza A virus at 31 μM, the highest concentration tested. Next, whether VX-497 has any direct or indirect effect on the IFN-α signaling pathway was determined. To this end L929 cells and EMCV-infected L929 cells were treated with IFN-α alone and with IFN-α supplemented with VX-497. No noticeable difference in pattern or intensity of gelretarded bands (data not shown) was observed when the experiments were repeated with the addition of VX-497 (range, 100 to 500 nM). This suggests that VX-497 does not alter, positively or negatively, the IFN-α signaling pathway in L929 cells and that the antiviral effect of VX-497 in the EMCV replication system is indeed independent.
Antimicrob Agents Chemother. 2000 Apr; 44(4): 859–866. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC89783/
In vivo activity:
In the skin transplant study, trunk skin grafts from Balb/c mice were grafted onto C57Bl/6 mice. Mice were administered vehicle or VX-497 twice daily until day 10. Mean survival of skin grafts on vehicle-treated animals was 9.9 +/- 0.9 days. Graft survival was prolonged significantly in animals treated with VX-497 to 13.2 +/- 1.2 (p < 0.001, Kaplan Meier Log-Rank test) days in the 50 mg/kg group and 13.9 +/- 1.0 (p < 0.001) days in the 85 mg/kg group. In the GVHD study, 150 x 10(6) nonadherent splenocytes from B6 mice were injected intravenously into the F1 hybrid strain B6DBA/2. Groups of animals (n = 6) were administered vehicle or 50 or 100 mg/kg VX-497 b.i.d for 8 days. GVHD developed in the vehicle-treated allografted F1 mice and treatment with VX-497 improved all manifestations of the disease significantly. The 2.9-fold increase in spleen weight in allografted animals was reduced to a 1.6-fold increase in the VX-497-treated mice. Serum IFN-gamma levels were increased 54-fold in the vehicle group while there was a 7.4-fold increase in VX-497-treated animals. Spontaneous spleen cell proliferation was increased 9.9-fold in the absence of VX-497 and there was a 3.5-fold increase in its presence. Thus, VX-497 has been shown to be effective in both a skin transplantation and a GVHD model in the mouse. The demonstrated pharmacological activity of VX-497 in these murine transplantation models warrants further evaluation of the drug in transplantation indications.
Drugs Exp Clin Res. 2001;27(3):89-95. https://pubmed.ncbi.nlm.nih.gov/11447770/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
50.0 |
110.51 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
452.46
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
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. doi: 10.1128/AAC.44.4.859-866.2000. PMID: 10722482; PMCID: PMC89783. 2. Zhou S, Liu R, Baroudy BM, Malcolm BA, Reyes GR. The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA. Virology. 2003 Jun 5;310(2):333-42. doi: 10.1016/s0042-6822(03)00152-1. PMID: 12781720.
3. Decker CJ, Heiser AD, Chaturvedi PR, Faust TJ, Ku G, Moseley S, Nimmesgern E. The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice. Drugs Exp Clin Res. 2001;27(3):89-95. PMID: 11447770.
4. Li SF, Gong MJ, Shao JJ, Sun YF, Zhang YG, Chang HY. Antiviral activity of merimepodib against foot and mouth disease virus in vitro and in vivo. Mol Immunol. 2019 Oct;114:226-232. doi: 10.1016/j.molimm.2019.07.021. Epub 2019 Aug 3. PMID: 31386979.
In vitro protocol:
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. doi: 10.1128/AAC.44.4.859-866.2000. PMID: 10722482; PMCID: PMC89783. 2. Zhou S, Liu R, Baroudy BM, Malcolm BA, Reyes GR. The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA. Virology. 2003 Jun 5;310(2):333-42. doi: 10.1016/s0042-6822(03)00152-1. PMID: 12781720.
In vivo protocol:
1. Decker CJ, Heiser AD, Chaturvedi PR, Faust TJ, Ku G, Moseley S, Nimmesgern E. The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice. Drugs Exp Clin Res. 2001;27(3):89-95. PMID: 11447770. 2. Li SF, Gong MJ, Shao JJ, Sun YF, Zhang YG, Chang HY. Antiviral activity of merimepodib against foot and mouth disease virus in vitro and in vivo. Mol Immunol. 2019 Oct;114:226-232. doi: 10.1016/j.molimm.2019.07.021. Epub 2019 Aug 3. PMID: 31386979.
1: McHutchison JG, Shiffman ML, Cheung RC, Gordon SC, Wright TL, Pottage JC Jr, McNair L, Ette E, Moseley S, Alam J. A randomized, double-blind, placebo-controlled dose-escalation trial of merimepodib (VX-497) and interferon-alpha in previously untreated patients with chronic hepatitis C. Antivir Ther. 2005;10(5):635-43. PubMed PMID: 16152757.
2: Decker CJ, Heiser AD, Chaturvedi PR, Faust TJ, Ku G, Moseley S, Nimmesgern E. The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice. Drugs Exp Clin Res. 2001;27(3):89-95. PubMed PMID: 11447770.
3: Phase II clinical trial of VX-497 for HCV infection begins. AIDS Patient Care STDS. 1998 Dec;12(12):944. PubMed PMID: 11362074.
4: 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. PubMed PMID: 11288107.
5: 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. PubMed PMID: 10722482; PubMed Central PMCID: PMC89783.
