Zapnometinib

Zapnometinib
Clinical data
Other namesATR002, PD-0184264
Drug classMek inhibitor
Identifiers
  • 2-(2-chloro-4-iodoanilino)-3,4-difluorobenzoic acid
CAS Number
PubChem CID
IUPHAR/BPS
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.351.768
Chemical and physical data
FormulaC13H7ClF2INO2
Molar mass409.56 g·mol−1
3D model (JSmol)
  • C1=CC(=C(C=C1I)Cl)NC2=C(C=CC(=C2F)F)C(=O)O
  • InChI=1S/C13H7ClF2INO2/c14-8-5-6(17)1-4-10(8)18-12-7(13(19)20)2-3-9(15)11(12)16/h1-5,18H,(H,19,20)
  • Key:XCNBGWKQXRQKSA-UHFFFAOYSA-N

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

  1. ↑ Lorusso PM, Adjei AA, Varterasian M, Gadgeel S, Reid J, Mitchell DY, et al. (August 2005). "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. doi:10.1200/JCO.2005.14.415. PMID 16009947.
  2. ↑ "Atriva Therapeutics receives U.S. FDA Orphan Drug Designation for Zapnometinib to treat Hantavirus Infections". BioRegio STERN Management GmbH.
  3. ↑ Füll Y, Wallasch C, Hilton A, Planz O (2022). "Pharmacokinetics, absorption, distribution, metabolism and excretion of the MEK inhibitor zapnometinib in rats". Frontiers in Pharmacology. 13 1050193. doi:10.3389/fphar.2022.1050193. PMC 9760738. PMID 36545320.
  4. 1 2 Ludwig S, Pleschka S, Planz O (April 2023). "MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases". Current Opinion in Virology. 59 101304. doi:10.1016/j.coviro.2023.101304. PMC 10091867. PMID 36841033.
  5. ↑ Koch-Heier J, Schönsiegel A, Waidele LM, Volk J, Füll Y, Wallasch C, et al. (2022). "Pharmacokinetics, Pharmacodynamics and Antiviral Efficacy of the MEK Inhibitor Zapnometinib in Animal Models and in Humans". Frontiers in Pharmacology. 13 893635. doi:10.3389/fphar.2022.893635. PMC 9240354. PMID 35784712.
  6. ↑ Hoffmann H, Ebensperger M, Schönsiegel A, Hamza H, Koch-Heier J, Schreiber A, et al. (2023). "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 1264983. doi:10.3389/fcimb.2023.1264983. PMC 10641236. PMID 37965261.
  7. ↑ Rohde G, Stenglein S, Prozesky H, Manudhane G, Sandulescu O, Bauer M, et al. (November 2023). "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 102237. doi:10.1016/j.eclinm.2023.102237. PMC 10725048. PMID 38106555.
  8. ↑ Schreiber A, Rodner F, Oberberg N, Anhlan D, Bletz S, Mellmann A, et al. (May 2024). "The host-targeted antiviral drug Zapnometinib exhibits a high barrier to the development of SARS-CoV-2 resistance". Antiviral Research. 225 105840. doi:10.1016/j.antiviral.2024.105840. PMID 38438015.
  9. ↑ Schreiber A, Oberberg N, Ambrosy B, Rodner F, Kumar S, Caliskan DM, et al. (December 2025). "Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib". Emerging Microbes & Infections. 14 (1) 2471022. doi:10.1080/22221751.2025.2471022. PMC 11915740. PMID 39976482.
  10. ↑ Füll Y, Schüssele LM, Hamza H, Hoffmann H, Bauer M, Stenglein S, et al. (2025). "Antiviral and immunomodulatory effect of zapnometinib in animal models and hospitalized COVID-19 patients". Frontiers in Immunology. 16 1631721. doi:10.3389/fimmu.2025.1631721. PMC 12498288. PMID 41058679.
This page is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.