IMP-1088

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]

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

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]