Abstract
Protein-protein interactions (PPIs) are central to a variety of biological processes, and their dysfunction is implicated in the pathogenesis of a range of human diseases, including cancer. Hence, the inhibition of PPIs has attracted significant attention in drug discovery. Covalent inhibitors have been reported to achieve high efficiency through forming covalent bonds with cysteine or other nucleophilic residues in the target protein. Evidence suggests that there is a reduced risk for the development of drug resistance against covalent drugs, which is a major challenge in areas such as oncology and infectious diseases. Recent improvements in structural biology and chemical reactivity have enabled the design and development of potent and selective covalent PPI inhibitors. In this review, we will highlight the design and development of therapeutic agents targeting PPIs for cancer therapy.
Highlights
The protein-protein interaction (PPI) is defined as a physical link between a protein and its partner(s) [1,2,3]
In leukemia, the mixed lineage leukemia (MLL) protein interacts with menin to promote oncogenic activity
Developing small molecule inhibitors to directly disrupt the MLL-menin interaction is a potential strategy for leukemia treatment [100, 101]
Summary
The protein-protein interaction (PPI) is defined as a physical link between a protein and its partner(s) [1,2,3]. These connections may display a range of heterogeneities and complexities in macromolecular structures, forming protein dimers, multicomponent complexes, or long chains [4]. There are nearly 650,000 PPIs in humans, and this number continues to increase as more interaction networks become discovered [3, 7]. The function of proteins plays an essential role in the context of PPI networks [5]. The PPI system connects different enzymes with their protein substrates and regulates the activity of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
