Between Theory and Practice: Computational/Experimental Integrated Approaches to Understand the Solubility and Lipophilicity of PROTACs.

Emerging drug candidates more often fall in the beyond-rule-of-five chemical space. Among them, proteolysis targeting chimeras (PROTACs) have gained great attention in the past decade. Although physicochemical properties of small molecules accomplishing Lipinski's rule-of-five can now be easily predicted through models generated by large data collections, for PROTACs the knowledge is still limited and heterogeneous, hampering their prediction. Here, the kinetic solubility and the coefficient of distribution at pH 7.4 (LogD