IMP-1088

IMP-1088
Identifiers
	IUPAC name 1-(5-{3,4-Difluoro-2-[2-(1,3,5-trimethyl-1''H''-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1''H''-indazol-3-yl)-''N'',''N''-dimethylmethanamine;
CAS Number	2059148-82-0;
PubChem CID	132274735;
ChemSpider	65326081;
UNII	ZT62NQ6YEV;
ChEMBL	ChEMBL4445137;
PDB ligand	KFK (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID301336328 ;
Chemical and physical data
Formula	C25H29F2N5O
Molar mass	453.538 g·mol−1
3D model (JSmol)	Interactive image;
	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. It prevents the production of infectious virus particles by targeting host cell machinery rather than the virus itself. Specifically, it inhibits the host's NMT enzymes, blocking the myristoylation of viral proteins required for capsid assembly. Since this strategy acts on host proteins, it is thought to carry a lower risk of viral resistance.^[1]^[2]

Antiviral activity

IMP-1088 blocks the replication of viruses that rely on myristoylated proteins for their life cycle, including poxviruses, mammarenaviruses, and rhinoviruses.^[3]^[4]^[5] This approach has been explored for potential treatment of monkeypox, Lassa fever, and the common cold.

Mammarenaviruses

The inhibitor has demonstrated activity against mammarenaviruses such as LCMV and hemorrhagic fever viruses including Lassa and Junin. In these viruses, IMP-1088 targets myristoylated proteins such as the Z matrix protein and the signal peptide of glycoprotein 1, both essential for viral assembly, budding, and propagation.^[4]

Poxviruses

In poxviruses such as vaccinia and monkeypox, inhibition of myristoylation disrupts the function of four essential myristoylated viral proteins. In combination therapies, this has been shown to completely inhibit viral replication.^[5]

Research applications

In addition to its antiviral potential, IMP-1088 has been used as a research tool to study viral protein function. It has been shown that myristoylation and oligomerization are not required for the Z matrix protein’s dose-dependent inhibitory effect on viral ribonucleoprotein (vRNP) activity.^[6]

References

^ Borman S. "Agent stops common cold virus replication". Chemical & Engineering News. Retrieved 20 May 2018.
^ 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.
^ 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.
^ ^a ^b 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.
^ ^a ^b 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. PMC 11769280. PMID 39861882.
^ Witwit H, de la Torre JC (2025-04-29). "Mammarenavirus Z Protein Myristoylation and Oligomerization Are Not Required for Its Dose-Dependent Inhibitory Effect on vRNP Activity". BioChem. 5 (2): 10. doi:10.3390/biochem5020010. ISSN 2673-6411. PMC 12163724.

[1] Borman S. "Agent stops common cold virus replication". Chemical & Engineering News. Retrieved 20 May 2018.

[2] 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.

[3] 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.

[Witwit_2024-4] 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.

[Witwit_2025-5] 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. PMC 11769280. PMID 39861882.

[6] Witwit H, de la Torre JC (2025-04-29). "Mammarenavirus Z Protein Myristoylation and Oligomerization Are Not Required for Its Dose-Dependent Inhibitory Effect on vRNP Activity". BioChem. 5 (2): 10. doi:10.3390/biochem5020010. ISSN 2673-6411. PMC 12163724.

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