A patent review of mitogen-activated protein kinase-interacting kinases (MNKs) modulators (2019-present)

Abstract

Introduction: The mitogen-activated protein kinase interacting kinases (MNKs) modulate protein translation through the phosphorylation of eukaryotic initiation factor 4E (eIF4E) at serine 209, which is crucial for tumorigenesis but dispensable for normal development. MNKs are implicated in various pathological processes, including inflammation, obesity, cancer, etc. Thus, MNKs are considered as potential drug targets and the development of potent and selective MNK inhibitors is a current research focus.

Areas covered: This review covers inhibitors of MNKs reported in patents published in the online databases of the World Intellectual Property Organization and European Patent Office from 2019 to 2024. This review provides a landscape of available inhibitors, including their chemical structures, activity, and stage of development.

Expert opinion: In recent years, highly potent and selective inhibitors have been discovered and many of them show promising results in several preclinical cancer models. The majority of small-molecule inhibitors developed recently, similarly to the structure of eFT508 and ETC-206. Also, some new skeletons were disclosed and showed novel mechanisms, including non-traditional ATP competition and induced protein degradation by proteolysis targeting chimeras. Ongoing preclinical research and clinical trials will provide us more information on these new compounds and MNKs novel functions beyond cancer.

Keywords: MNK; anti-cancer; combination therapy; eIF4E; inflammation; metabolism.