IMP-1088

IMP-1088 is a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 with IC₅₀ value of 0.24nM and NMT2 ith IC₅₀ value < 1nM.^[1]. IMP-1088 exhibits broad-spectrum antiviral potential, targeting mammarenaviruses, respiratory rhinoviruses, and malaria parasites^[2][3].

In vitro, IMP-1088 exposure (1mM to 0.1pM) on breast cancer MDA-MB-231 cells and cervical cancer HeLa cells for 24, 48 or 72h affected proliferation of MDA-MB-231 and HELA cells only after 48 and 72h and in a concentration-dependent manner. IMP-1088 exposure (1μM) for 18h significantly inhibited N-myristoylation of the majority of NMT substrate proteins identified but did not reduce protein synthesis or alter cell cycles^[4]. IMP-1088 (1μM) treated HEK293T cells transfected with plasmids expressing lymphocytic choriomeningitis virus polymerase proteins and nucleoprotein for 24h targeting Z protein myristoylation impairs virus assembly and budding without affecting Z-mediated inhibition of viral ribonucleoprotein (vRNP) activity^[5]. IMP-1088 (0.001-100μM) treated HeLa cells infected with Vaccinia virus (VACV) for 24h caused a reduction of > 50% in both virus yield and viral spread at approximately 100nM, without cellular toxicity observed in the presence of up to 10μM IMP-1088^[6].

References:
[1] Mousnier A, Bell A S, Swieboda D P, et al. Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus. Nat Chem. 2018 Jun;10(6):599-606.
[2] Agoni C, Salifu E Y, Enslin G, Kwofie S K, Soliman M E. Dual-Inhibition of Human N-Myristoyltransferase Subtypes Halts Common Cold Pathogenesis: Atomistic Perspectives from the Case of IMP-1088. Chem Biodivers. 2022 Feb;19(2):e2021007.
[3] Mendez A, Bolling C, Taylor S, et al. Structure of Plasmodium vivax N-myristoyltransferase with inhibitor IMP-1088: exploring an NMT inhibitor for antimalarial therapy. Acta Crystallogr F Struct Biol Commun. 2025 Jan 1;81(Pt 1):1-10.
[4] Kallemeijn W W, Lueg G A, Faronato M, et al. Validation and Invalidation of Chemical Probes for the Human N-myristoyltransferases. Cell Chem Biol. 2019 Jun 20;26(6):892-900.e4.
[5] Witwit H, de la Torre J C. Mammarenavirus Z Protein Myristoylation and Oligomerization Are Not Required for Its Dose-Dependent Inhibitory Effect on vRNP Activity. Biochem (Basel). 2025 Jun;5(2):10.
[6] Priyamvada L, Kallemeijn W W, Faronato M, et al. Inhibition of vaccinia virus L1 N-myristoylation by the host N-myristoyltransferase inhibitor IMP-1088 generates non-infectious virions defective in cell entry. PLoS Pathog. 2022 Oct 10;18(10):e1010662.

IMP-1088是一种针对人类N-豆蔻酰转移酶NMT1和NMT2的皮摩尔级双重抑制剂，对NMT1的IC₅₀值为0.24nM，对NMT2的IC₅₀值 < 1nM。IMP-1088在药理学上可迅速且完全抑制宿主细胞的N-豆蔻酰化，从而在不引起细胞毒性的情况下完全阻断鼻病毒复制。IMP-1088以剂量依赖性方式阻断病毒诱导的细胞病变，其IC₅₀值为17nM^[1][4]。IMP-1088具有广谱抗病毒潜力，可靶向乳腺病毒、呼吸道鼻病毒及疟原虫^[2][3]。

IMP-1088 (1mM至0.1pM) 作用于乳腺癌MDA-MB-231和宫颈癌HeLa细胞24、48或72h，仅在48和72h后以浓度依赖性方式影响细胞增殖。 IMP-1088 (1μM) 处理18h显著抑制大多数NMT底物蛋白的N-豆蔻酰化，但不降低蛋白合成或改变细胞周期^[4]。 IMP-1088 (1μM) 处理转染了表达淋巴细胞性脉络丛脑膜炎病毒聚合酶蛋白和核蛋白质粒的HEK293T细胞24h，靶向病毒基质蛋白Z蛋白豆蔻酰化并干扰病毒组装与出芽，而不影响Z蛋白介导的病毒核糖核蛋白 (vRNP) 活性抑制^[5]。 IMP-1088 (0.001–100μM) 处理Vaccinia病毒感染的HeLa细胞24h，在约100nM时使病毒产量和扩散均下降>50%，且10μM以内无细胞毒性^[6]。