| Abstrakt: |
Protein-protein interactions (PPIs) aSre pivotal in biology and present promising therapeutic opportunities. This review focuses on recent strides in developing small molecule PPI inhibitors, emphasizing their structural insights, mechanisms, and clinical applications. Small molecules possess distinct advantages, including oral administration convenience, cell penetration, chemical diversity, and cost-effectiveness, making them vital in drug discovery. Methods to target PPIs span high-throughput screening, structure-based design, fragment-based discovery, computational tools, and chemical biology techniques. Case studies illustrate successful inhibitors, spotlighting specific targets and mechanisms. Innovative screening platforms like phenotypic screening, covalent inhibitors, PROTACs and molecular glues are examined alongside structural revelations enabled by Cryo-electron microscopy and X-ray crystallography. Elevating selectivity in small molecule PPI inhibitors remains pivotal. Challenges, including druggability, toxicity, resistance and regulatory intricacies are acknowledged. The future landscape encompasses target identification, systems biology integration, personalized medicine, and therapeutic potential in traditionally elusive targets. The review also traverses clinical applications and the PPI inhibitor pipeline, including compounds in trials and approved drugs. Safety assessments, comprising predictive models and pharmacokinetics/pharmacodynamics studies, ensure the secure and efficient development of PPI inhibitors. In summary, this review offers a comprehensive exploration of small molecule inhibitors for PPIs in drug discovery, underlining their transformative potential, persisting challenges, and auspicious applications across diverse disease contexts. [ABSTRACT FROM AUTHOR] |
