RESUMEN
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.
RESUMEN
About 60% to 70% of people with dementia have Alzheimer's Disease (AD), a neurodegenerative illness. One reason for this disorder is the misfolding of naturally occurring proteins in the human brain, specifically ß-amyloid (Aß) and tau. Certain diagnostic imaging techniques, such as amyloid PET imaging, tau PET imaging, Magnetic Resonance Imaging (MRI), Computerized Tomography (CT), and others, can detect biomarkers in blood, plasma, and cerebral spinal fluids, like an increased level of ß-amyloid, plaques, and tangles. In order to create new pharmacotherapeutics for Alzheimer's disease, researchers must have a thorough and detailed knowledge of amyloid beta misfolding and other related aspects. Donepezil, rivastigmine, galantamine, and other acetylcholinesterase inhibitors are among the medications now used to treat Alzheimer's disease. Another medication that can temporarily alleviate dementia symptoms is memantine, which blocks the N-methyl-D-aspartate (NMDA) receptor. However, it is not able to halt or reverse the progression of the disease. Medication now on the market can only halt its advancement, not reverse it. Interventions to alleviate behavioral and psychological symptoms, exhibit anti- neuroinflammation and anti-tau effects, induce neurotransmitter alteration and cognitive enhancement, and provide other targets have recently been developed. For some Alzheimer's patients, the FDA-approved monoclonal antibody, aducanumab, is an option; for others, phase 3 clinical studies are underway for drugs, like lecanemab and donanemab, which have demonstrated potential in eliminating amyloid protein. However, additional study is required to identify and address these limitations in order to reduce the likelihood of side effects and maximize the therapeutic efficacy.