Merimepodib

Merimepodib
Legal status
Legal status	US: Investigational drug;
Identifiers
	IUPAC name [(3S)-oxolan-3-yl] N-[(3-{[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoylamino}phenyl)methyl]carbamate;
CAS Number	198821-22-6;
PubChem CID	153241;
DrugBank	DB04862;
ChemSpider	135060;
UNII	2ZL2BA06FU;
KEGG	D04936;
ChEMBL	ChEMBL304087;
CompTox Dashboard (EPA)	DTXSID70173639 ;
Chemical and physical data
Formula	C23H24N4O6
Molar mass	452.467 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC1=C(C=CC(=C1)NC(=O)NC2=CC=CC(=C2)CNC(=O)O[C@H]3CCOC3)C4=CN=CO4;
	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; Key: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]^[7] 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".^[8]

References

^ Jain J, Almquist SJ, Shlyakhter D, Harding MW (May 2001). "VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent". Journal of Pharmaceutical Sciences. 90 (5): 625–637. doi:10.1002/1520-6017(200105)90:5<625::aid-jps1019>3.0.co;2-1. PMID 11288107.
^ McHutchison JG, Shiffman ML, Cheung RC, Gordon SC, Wright TL, Pottage JC, et al. (2005). "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. doi:10.1177/135965350501000503. PMID 16152757. S2CID 237218077.
^ Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, et al. (December 2009). "Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders". Hepatology. 50 (6): 1719–1726. doi:10.1002/hep.23204. PMID 19852040. S2CID 2497811.
^ Tong X, Smith J, Bukreyeva N, Koma T, Manning JT, Kalkeri R, et al. (January 2018). "Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens". Antiviral Research. 149: 34–40. doi:10.1016/j.antiviral.2017.11.004. PMID 29126899. S2CID 46843542.
^ Li SF, Gong MJ, Shao JJ, Sun YF, Zhang YG, Chang HY (October 2019). "Antiviral activity of merimepodib against foot and mouth disease virus in vitro and in vivo". Molecular Immunology. 114: 226–232. doi:10.1016/j.molimm.2019.07.021. hdl:2268/248312. PMID 31386979. S2CID 199469162.
^ Clinical trial number NCT04410354 for "Study of Merimepodib in Combination With Remdesivir in Adult Patients With Advanced COVID-19 " at ClinicalTrials.gov
^ Arunachalam R, Kumar KP (10 July 2020). "COVID-19: Clinical Trials and Potential Therapeutic Agents - A Narrative Review". SSRN from Elsevier. SSRN 3653031. Retrieved 14 August 2020.
^ "ViralClear halts its Phase 2 Hospitalized COVID-19 Trial". BioSig Technologies, Inc. (BSGM). 26 October 2020.

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[pmid11288107-1] Jain J, Almquist SJ, Shlyakhter D, Harding MW (May 2001). "VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent". Journal of Pharmaceutical Sciences. 90 (5): 625–637. doi:10.1002/1520-6017(200105)90:5<625::aid-jps1019>3.0.co;2-1. PMID 11288107.

[pmid16152757-2] McHutchison JG, Shiffman ML, Cheung RC, Gordon SC, Wright TL, Pottage JC, et al. (2005). "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. doi:10.1177/135965350501000503. PMID 16152757. S2CID 237218077.

[pmid19852040-3] Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, et al. (December 2009). "Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders". Hepatology. 50 (6): 1719–1726. doi:10.1002/hep.23204. PMID 19852040. S2CID 2497811.

[pmid29126899-4] Tong X, Smith J, Bukreyeva N, Koma T, Manning JT, Kalkeri R, et al. (January 2018). "Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens". Antiviral Research. 149: 34–40. doi:10.1016/j.antiviral.2017.11.004. PMID 29126899. S2CID 46843542.

[pmid31386979-5] Li SF, Gong MJ, Shao JJ, Sun YF, Zhang YG, Chang HY (October 2019). "Antiviral activity of merimepodib against foot and mouth disease virus in vitro and in vivo". Molecular Immunology. 114: 226–232. doi:10.1016/j.molimm.2019.07.021. hdl:2268/248312. PMID 31386979. S2CID 199469162.

[6] Clinical trial number NCT04410354 for "Study of Merimepodib in Combination With Remdesivir in Adult Patients With Advanced COVID-19 " at ClinicalTrials.gov

[7] Arunachalam R, Kumar KP (10 July 2020). "COVID-19: Clinical Trials and Potential Therapeutic Agents - A Narrative Review". SSRN from Elsevier. SSRN 3653031. Retrieved 14 August 2020.

[8] "ViralClear halts its Phase 2 Hospitalized COVID-19 Trial". BioSig Technologies, Inc. (BSGM). 26 October 2020.

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