MEK inhibitors in oncology: a patent review and update (2016 - present).

INTRODUCTION: Mitogen-activated protein kinase (MEK) is one of the important components of Ras/Raf/MEK/ERK signaling pathway, transduces signal for cell growth, differentiation, and development. Deregulation of MEK leads to a wide variety of cancer, hence MEK is considered as potential therapeutic targets for the treatment of cancer. The MEK1/2 inhibitors in combination with other inhibitors showed better therapeutic outcomes in various malignancies including resistant or relapsed or refractory cancer.

AREAS COVERED: A comprehensive patent literature from the year 2016 to May 2024 on MEK inhibitors in oncology, their combination products and structural insights have been reviewed through searching relevant information in PubMed, Scopus, Espacenet, Web of Science, World Intellectual Property Organization and Google Patent databases.

EXPERT OPINION: Overexpression and mutation of MEK have been reported to cause a wide variety of cancers especially resistant cancers. The MEK1/2 inhibitors in combination with other kinase (BRaf/KRas/PI3K) inhibitors showed significant anti-proliferative activity. Other combination of MEK inhibitor with PD-1, DYRK1, EGFR, BTK and/or VEGF inhibitors etc. showed promising results in many cancers including colorectal, pancreatic, gastrointestinal, solid tumor, breast cancer, melanoma and multiple myeloma etc. The dual or multi-targeted approaches of these combinations showed better and precise treatment of patients with resistant cancer.