Chemistry:Zapnometinib
Zapnometinib (PD-0184264, ATR-002) is a pharmaceutical drug which is a selective MEK inhibitor.
It is the active carboxylic acid metabolite of CI‑1040 (PD‑184352), a first‑generation MEK1/2 inhibitor originally developed by Pfizer for oncology indications.[1] It was subsequently repurposed and clinically advanced by Atriva Therapeutics GmbH[2] as a host‑targeted antiviral drug against RNA viruses whose mechanism of action is complemented by immunomodulatory effects.[3]
Zapnometinib acts as a host‑targeted antiviral by inhibiting cellular MEK1/2 in the Raf/MEK/ERK signaling cascade, a pathway many RNA viruses co‑opt to complete their replication cycle. Blocking MEK1/2 prevents efficient nuclear export and assembly of viral ribonucleoprotein complexes.[4]
It has potential applications in the treatment of cancer, but has mainly been investigated for its antiviral properties, showing activity against several acute viral infections such as influenza, COVID-19 and hantavirus.[5][4][6][7][8][9][10]
See also
References
- ↑ "Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies". Journal of Clinical Oncology 23 (23): 5281–5293. August 2005. doi:10.1200/JCO.2005.14.415. PMID 16009947.
- ↑ "Atriva Therapeutics receives U.S. FDA Orphan Drug Designation for Zapnometinib to treat Hantavirus Infections.". BioRegio STERN Management GmbH. https://www.bioregio-stern.de/en/news/atriva-therapeutics-receives-us-fda-orphan-drug-designation-for-zapnometinib-to-treat.
- ↑ "Pharmacokinetics, absorption, distribution, metabolism and excretion of the MEK inhibitor zapnometinib in rats". Frontiers in Pharmacology 13. 2022. doi:10.3389/fphar.2022.1050193. PMID 36545320.
- ↑ 4.0 4.1 "MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases". Current Opinion in Virology 59. April 2023. doi:10.1016/j.coviro.2023.101304. PMID 36841033.
- ↑ "Pharmacokinetics, Pharmacodynamics and Antiviral Efficacy of the MEK Inhibitor Zapnometinib in Animal Models and in Humans". Frontiers in Pharmacology 13. 2022. doi:10.3389/fphar.2022.893635. PMID 35784712.
- ↑ "Influenza A virus replication has a stronger dependency on Raf/MEK/ERK signaling pathway activity than SARS-CoV-2". Frontiers in Cellular and Infection Microbiology 13. 2023. doi:10.3389/fcimb.2023.1264983. PMID 37965261.
- ↑ "Efficacy and safety of zapnometinib in hospitalised adult patients with COVID-19 (RESPIRE): a randomised, double-blind, placebo-controlled, multicentre, proof-of-concept, phase 2 trial". EClinicalMedicine 65. November 2023. doi:10.1016/j.eclinm.2023.102237. PMID 38106555.
- ↑ "The host-targeted antiviral drug Zapnometinib exhibits a high barrier to the development of SARS-CoV-2 resistance". Antiviral Research 225. May 2024. doi:10.1016/j.antiviral.2024.105840. PMID 38438015.
- ↑ "Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib". Emerging Microbes & Infections 14 (1). December 2025. doi:10.1080/22221751.2025.2471022. PMID 39976482.
- ↑ "Antiviral and immunomodulatory effect of zapnometinib in animal models and hospitalized COVID-19 patients". Frontiers in Immunology 16. 2025. doi:10.3389/fimmu.2025.1631721. PMID 41058679.
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