Chemistry for the Identification of Therapeutic Targets: Recent Advances and Future Directions

The increasing availability of chemical probes for specific applications in chemical biology and medicinal chemistry is extensively facilitating our knowledge of biological systems. This understanding has fundamental implications in the development of new efficacious therapeutic strategies. Nowadays, successful drug discovery programs consider identification, engagement, and endogenous levels of the intended therapeutic target from the earliest preclinical stages. All these aspects are addressed with the use of chemical probes, compounds that rely on the use of a particular chemical reaction to give an answer to a specific biological question. In this review we will describe the underlying chemistry and the most recent advances experienced in the field together with their most important biomedical applications. The earliest preclinical stages of drug discovery must generate information about the identity, the in vivo engagement, and the endogenous levels of the targeted protein(s). In this review, we outline the main strategies by which chemical probes, compounds that rely on chemical reactions to give an answer to specific biological questions, are contributing to currently challenging biomedical applications.