Merimepodib

• CAT Number: I002524
• CAS Number: 198821-22-6
• Molecular Formula: C23H24N4O6
• Molecular Weight: 452.46
• Purity: ≥95%
• Target: HBV
• Solubility: DMSO: ≥ 31 mg/mL
• Storage: Store at -20C
• 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
• InChIKey: JBPUGFODGPKTDW-SFHVURJKSA-N
• SMILES: O=C(O[C@@H]1COCC1)NCC2=CC=CC(NC(NC3=CC=C(C4=CN=CO4)C(OC)=C3)=O)=C2

Merimepodiba(VX-497) is a novel noncompetitive inhibitor of IMPDH(Inosine monophosphate dehydrogenase).IC50 value:Target: IMP dehydrogenase; Antiviralin vitro: VX-497 (MW 452.5) is orally bioavailable and inhibits the proliferation of primary human, mouse, rat, and dog lymphocytes at concentrations of ~100 nM. The inhibitory effect of VX-497 on lymphocytes is reversed in the presence of exogenous guanosine, but not in the presence of adenosine or uridine, confirming that the antilymphocytic activity of VX-497 is specifically due to inhibition of IMPDH [1]. The effect of VX-497 on virus replication in the assays described above (Table (Table1)1) fell into three groups. 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 [2].in vivo: 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 [3].

Reference

1:Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders. Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, Bonkovsky HL, Bengtsson L, Chandorkar G, Harding M, McNair L, Aalyson M, Alam J, Kauffman R, Gharakhanian S, McHutchison JG; MErimepodib TRiple cOmbination Study Group..Hepatology. 2009 Dec;50(6):1719-26. doi: 10.1002/hep.23204. PMID: 19852040 2:Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C. Marcellin P, Horsmans Y, Nevens F, Grange JD, Bronowicki JP, Vetter D, Purdy S, Garg V, Bengtsson L, McNair L, Alam J.J Hepatol. 2007 Oct;47(4):476-83. Epub 2007 Jun 21. PMID: 17629590 3:A randomized, double-blind, placebo-controlled dose-escalation trial of merimepodib (VX-497) and interferon-alpha in previously untreated patients with chronic hepatitis C. McHutchison JG, Shiffman ML, Cheung RC, Gordon SC, Wright TL, Pottage JC Jr, McNair L, Ette E, Moseley S, Alam J.Antivir Ther. 2005;10(5):635-43. PMID: 16152757 4:Merimepodib (Vertex). Tossing G.IDrugs. 2003 Apr;6(4):372-6. Review. No abstract available. PMID: 12789609