Course Identification

1. The history of covalent inhibitors
2. Electrophiles and amino acid nucleophiles
3. Reactivity assessment
4. Covalent Hit discovery: 
   1. - Computational methods
   2. - Covalent fragment screening
   3. - Covalent Derivatization
   4. - Phenotypic screening vs target based screening
5. Activity based protein profiling 
6. Covalent proximity inducers
7. Medicinal chemistry of covalent hits
   1. Best practices (electrophile swaps, direct to biology, reactivity tuning)
   2. Characterization and proof of mechanism
   3. Kinetics (Ki/Kinact), jump dilution
8. In vivo PK/PD, stability of covalent inhibitors, toxicity
9. Chemical biology applications
10. Ligand directed chemistries
11. Covalent Drugs, examples and case studies

Students that finish this course should have a good grasp of the general principles and latest technologies for the discovery and development of covalent inhibitors for chemical biology and therapeutic applications. They should be able to critically evaluate reported covalent inhibitors in the literature to select the best tools for their research, as well as embark on a new discovery campaign against this favorite protein target.