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IMP-1088

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Pharmaceutical compound
IMP-1088
Identifiers
IUPAC name
  • 1-(5-{3,4-Difluoro-2-phenyl}-1-methyl-1''H''-indazol-3-yl)-''N'',''N''-dimethylmethanamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H29F2N5O
Molar mass453.538 g·mol
3D model (JSmol)
SMILES
  • CC1=C(C(=NN1C)C)CCOC2=C(C=CC(=C2F)F)C3=CC4=C(C=C3)N(N=C4CN(C)C)C
InChI
  • InChI=InChI=1S/C25H29F2N5O/c1-15-18(16(2)31(5)28-15)11-12-33-25-19(8-9-21(26)24(25)27)17-7-10-23-20(13-17)22(14-30(3)4)29-32(23)6/h7-10,13H,11-12,14H2,1-6H3
  • Key:SOXNKJCQBRQUMS-UHFFFAOYSA-N

IMP-1088 is an enzyme inhibitor of the human N-myristoyltransferases NMT1 and NMT2, an analog of Zelenirstat, capable of preventing viruses that require myristoylated proteins for their life cycle such as pox viruses, mammarenaviruses, and rhinoviruses , an area of research relating to potential treatment of the monkeypox, lassa fever, and common cold among others. IMP-1088 works to keep cells from generating infectious virus by targeting the cell instead of the rhinovirus itself. It does this by blocking the NMT protein of the host cell which prevents the virus from assembling its capsid, since viral capsid myristoylation by host NMT is essential for assembly. It is thought unlikely that viruses will evolve resistance to such an approach since IMP-1088 works against the human cell and not the virus. IMP-1088 can inhibit mammarenaviruses such as LCMV virus and the hemorragic fever viruses such as lassa and junin, where IMP-1088 targets the Z matrix protein and the signal peptide of glycoprotein 1 of these viruses, these myristoylated viral proteins are essential for the viral life cycle including assembly, budding and propagation. Both vaccinia and monkeypox viruses have four myristoylated proteins that can be targeted which would interrupt viral lifecycle, inhibition of myristoylation has been shown to completely inhibit viral propagation in combination therapies.

References

  1. Mousnier A, Bell AS, Swieboda DP, Morales-Sanfrutos J, Pérez-Dorado I, Brannigan JA, et al. (June 2018). "Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus". Nature Chemistry. 10 (6): 599–606. Bibcode:2018NatCh..10..599M. doi:10.1038/s41557-018-0039-2. PMC 6015761. PMID 29760414.
  2. Witwit H, Betancourt CA, Cubitt B, Khafaji R, Kowalski H, Jackson N, et al. (August 2024). "Cellular N-Myristoyl Transferases Are Required for Mammarenavirus Multiplication". Viruses. 16 (9): 1362. doi:10.3390/v16091362. PMC 11436053. PMID 39339839.
  3. Witwit H, Cubitt B, Khafaji R, Castro EM, Goicoechea M, Lorenzo MM, et al. (January 2025). "Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance". Viruses. 17 (1): 92. doi:10.3390/v17010092. ISSN 1999-4915.
  4. Borman S. "Agent stops common cold virus replication". Chemical & Engineering News. Retrieved 20 May 2018.
  5. Houser K (19 May 2018). "A team of researchers may have actually found a cure to the common cold". Business Insider. Retrieved 20 May 2018.
  6. Witwit H, Betancourt CA, Cubitt B, Khafaji R, Kowalski H, Jackson N, et al. (August 2024). "Cellular N-Myristoyl Transferases Are Required for Mammarenavirus Multiplication". Viruses. 16 (9): 1362. doi:10.3390/v16091362. PMC 11436053. PMID 39339839.
  7. Witwit H, Cubitt B, Khafaji R, Castro EM, Goicoechea M, Lorenzo MM, et al. (January 2025). "Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance". Viruses. 17 (1): 92. doi:10.3390/v17010092. ISSN 1999-4915.
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