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Time to Get Turned on by Chemical Biology
Author(s) -
Long Marcus J. C.
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000497
Subject(s) - chemical biology , function (biology) , gain of function , pharmacophore , small molecule , drug discovery , protein function , computational biology , occupancy , nanotechnology , biochemical engineering , chemistry , computer science , biology , biochemistry , microbiology and biotechnology , engineering , materials science , mutation , ecology , gene
The pressing need for innovation in drug discovery is spurring the emergence of drugs that turn on protein function, as opposed to shutting activity down. Several pharmacophores usher protein target gain‐of‐function, for instance: PROTACs promote protein target degradation; other drug candidates have been reported to function through dominant‐negative inhibition of their target enzyme. Such classes of molecules are typically active at low target occupancy and display numerous advantages relative to canonical inhibitors, whose function is intrinsically tied to achieving, or exceeding a threshold occupancy. However, our ability to generally tap into gain‐of‐function processes through small molecule interventions is overall in its infancy. Herein, I outline how chemical biology is poised to help us bring this powerful idea to fruition. I further outline means through which gain‐of‐function events can be identified and harnessed.