Marine‐Derived Molecular Glue Degraders: A New Frontier in Targeted Protein Degradation for Treatment of Multi‐Factorial Diseases
Vajagathali Mohammed, B. Haridevamuthu, Kathiravan Muthu Kumaradoss, S. Karthick Raja Namasivayam, Jesu Arockiaraj
Abstract
Targeted protein degradation has emerged as a revolutionary approach to the selective elimination of disease-causing proteins that provides new strategies in the treatment of a variety of conditions. Currently, two major techniques in this area are known as proteolysis targeting chimeras (PROTACs) and molecular glue degraders (MGDs). MGDs can be natural or of synthetic origin, and only limited studies were performed with marine-derived MGDs. The study is a representation of the systematic review of literature in databases like Scopus, Web of Science, and PubMed about the MGDs from marine sources and deals with an outline of their therapeutic applications. MGDs derived from the ocean have shown great promise in infectious diseases, autoimmune disorders, cancer, and neurotoxicity-related disorders. Among them are Manumycin A against breast cancer and Khalalide F for treating neurotoxicity. Their identification and characterization are enormous challenges that, notwithstanding the therapeutic promise of MGDs, require advanced technologies and very specialized skills. Their development process is also complex legally and ethically given the imperative to access and use marine genetic resources within the parameters of the Nagoya Protocol on Access and Benefit Sharing. By setting a limit to the exploitation of genetic materials, in this case, marine genetic resources, further research developments in this particular area have especially become difficult due to the Nagoya Protocol. Marine-derived MGDs are opening a new frontier in drug discovery for the treatment of multi-factorial diseases with minimal/no side effects. Having the potential to revolutionize future treatment strategies, overcoming technical, legal, and ethical challenges will be important to realizing their full potential and assuring equitable access to such ground-breaking resources.