MNK

CGP 57380 is an inhibitor of MAP-kinase interacting kinase-1 (Mnk1, MKNK1) (IC50 = 2.2 uM).

Cercosporamide, an usnic amide, was originally identified in Cercosporidium henningsii as a host-selective phytotoxin and broad-spectrum antifungal agent and is a potent inhibitor of MAP-kinase interacting kinase-2 (Mnk2; IC50 = 11 nM), JAK3 (IC50 = 31), and Mnk1 (IC50 = 116 nM).

ETC-206 is a selective MNK1 and MNK2 inhibitor with IC50s of 64 nM and 86 nM, respectively.

SLV-2436 is a highly potent and ATP-competitive inhibitor of MNK1 and MNK2 with IC50s of 10.8 ?nM and 5.4 nM, respectively.

Tomivosertib (eFT508) is a potent, highly selective, and orally bioavailable MNK1 and MNK2 inhibitor, with IC50s of 1-2 nM against both isoforms.

QL-X-138 is a selective dual inhibitor of Bruton's tyrosine kinase (BTK) and MAPK-interacting kinase (MNK), demonstrating potent covalent binding to BTK and non-covalent binding to MNK. It exhibits IC50 values of 9.4 nM for BTK, and 107.4 nM and 26 nM for MNK1 and MNK2, respectively. Additionally, QL-X-138 displays antiviral activity against dengue virus serotype 2, with an IC50 of 3.5 μM. This compound is valuable for research involving B-cell malignancies and related therapeutic investigations.

HD202A is a selective dual inhibitor of MNK1 and MNK2, exhibiting IC50 values of 6.09 nM and 8.06 nM, respectively. This compound effectively inhibits the MNK-eIF4E signaling pathway, leading to downregulation of perilipin 2 and SCD1, while upregulating adipose triglyceride lipase and PPARγ coactivator 1α. HD202A enhances mitochondrial fatty acid oxidation, redox homeostasis, and demonstrates significant effects on metabolic health, including suppression of body weight gain, reduction in hepatic lipid accumulation, and improvement in glucose tolerance and insulin sensitivity. These properties make HD202A a valuable tool for researching metabolic dysfunction-associated steatotic liver disease.

MNK1/2-IN-7 is a selective inhibitor of MNK1 and MNK2, primarily targeting the MNK/eIF4E signaling pathway. This compound exhibits potent anticancer activity by effectively inhibiting the phosphorylation of eIF4E, which contributes to reduced cancer cell proliferation. Additionally, MNK1/2-IN-7 demonstrates favorable hERG safety profiles, making it a valuable tool for research applications in oncology, particularly in combination therapies with agents like Ibrutinib.