Merimepodib Explained

Iupac Name:	[(3''S'')-oxolan-3-yl] N-[(3-{[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoylamino}phenyl)methyl]carbamate
Legal Us:	Investigational drug
Cas Number:	198821-22-6
Pubchem:	153241
Unii:	2ZL2BA06FU
Chemspiderid:	135060
Chembl:	304087
Kegg:	D04936
Drugbank:	DB04862
C:	23
H:	24
N:	4
O:	6
Smiles:	COC1=C(C=CC(=C1)NC(=O)NC2=CC=CC(=C2)CNC(=O)O[C@H]3CCOC3)C4=CN=CO4
Stdinchi:	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
Stdinchikey:	JBPUGFODGPKTDW-SFHVURJKSA-N

Merimepodib (VX-497) is a drug which acts as an inhibitor of the enzyme inosine monophosphate dehydrogenase, which is required for the synthesis of nucleotide bases containing guanine. This consequently inhibits synthesis of DNA and RNA, and results in antiviral and immunosuppressive effects.^[1] It progressed as far as Phase 2b human clinical trials against Hepatitis C but showed only modest benefits in comparison to existing treatments,^{[2] [3]} however it continues to be researched, and also shows activity against other viral diseases such as Zika virus and foot and mouth disease virus.^{[4] [5]}

Merimepodib was investigated in combination with remdesivir in a phase 2 clinical trial in the U.S. as a potential treatment of COVID-19 by ViralClear Pharmaceuticals.^[6] The trial stopped in October 2020, and the company announced in a news release that it was "unlikely that the trial would meet its primary safety endpoints", and that it "does not intend to further develop merimepodib".^[7]

Notes and References

1. Jain J, Almquist SJ, Shlyakhter D, Harding MW . VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent . Journal of Pharmaceutical Sciences . 90 . 5 . 625–637 . May 2001 . 11288107 . 10.1002/1520-6017(200105)90:5<625::aid-jps1019>3.0.co;2-1 .
2. McHutchison JG, Shiffman ML, Cheung RC, Gordon SC, Wright TL, Pottage JC, McNair L, Ette E, Moseley S, Alam J . 6 . A randomized, double-blind, placebo-controlled dose-escalation trial of merimepodib (VX-497) and interferon-alpha in previously untreated patients with chronic hepatitis C . Antiviral Therapy . 10 . 5 . 635–643 . 2005 . 16152757 . 10.1177/135965350501000503 . 237218077 . free .
3. 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 . 6 . Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders . Hepatology . 50 . 6 . 1719–1726 . December 2009 . 19852040 . 10.1002/hep.23204 . 2497811 . free .
4. Tong X, Smith J, Bukreyeva N, Koma T, Manning JT, Kalkeri R, Kwong AD, Paessler S . 6 . Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens . Antiviral Research . 149 . 34–40 . January 2018 . 29126899 . 10.1016/j.antiviral.2017.11.004 . 46843542 .
5. 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 . Molecular Immunology . 114 . 226–232 . October 2019 . 31386979 . 10.1016/j.molimm.2019.07.021 . free . 199469162 . 2268/248312 .
6. Arunachalam R, Kumar KP . COVID-19: Clinical Trials and Potential Therapeutic Agents - A Narrative Review . SSRN from Elsevier . 10 July 2020 . 3653031 . 14 August 2020.
7. Web site: ViralClear halts its Phase 2 Hospitalized COVID-19 Trial . BioSig Technologies, Inc. (BSGM). 26 October 2020 .