Modulating biomolecular condensates: a novel approach to drug discovery. 2022

Diana M Mitrea, and Matthäus Mittasch, and Beatriz Ferreira Gomes, and Isaac A Klein, and Mark A Murcko
Dewpoint Therapeutics, Boston, MA, USA.

In the past decade, membraneless assemblies known as biomolecular condensates have been reported to play key roles in many cellular functions by compartmentalizing specific proteins and nucleic acids in subcellular environments with distinct properties. Furthermore, growing evidence supports the view that biomolecular condensates often form by phase separation, in which a single-phase system demixes into a two-phase system consisting of a condensed phase and a dilute phase of particular biomolecules. Emerging understanding of condensate function in normal and aberrant cellular states, and of the mechanisms of condensate formation, is providing new insights into human disease and revealing novel therapeutic opportunities. In this Perspective, we propose that such insights could enable a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and we discuss the strategies, techniques and challenges involved.

UI MeSH Term Description Entries
D009696 Nucleic Acids High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages. Nucleic Acid,Acid, Nucleic,Acids, Nucleic
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000091582 Biomolecular Condensates Membraneless intracellular compartments formed through liquid-liquid phase separation from the surrounding CYTOPLASM or nucleoplasm or by the concentration of proteins and nucleic acids into droplets as they aggregate on static cellular structures such as CELL MEMBRANES. Examples include CELL NUCLEOLI; STRESS GRANULES; PARASPECKLES; HISTONE LOCUS BODIES; and POSTSYNAPTIC DENSITIES. Membraneless Organelles,Biomolecular Condensate,Condensate, Biomolecular,Condensates, Biomolecular,Membraneless Organelle,Organelle, Membraneless,Organelles, Membraneless
D055808 Drug Discovery The process of finding chemicals for potential therapeutic use. Drug Prospecting,Discovery, Drug,Prospecting, Drug

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