A Perspective on the Strategic Application of Deconstruction–Reconstruction in Drug Discovery

The deconstruction of known ligands to proteins into smaller, often fragment-sized components and subsequent regrowth from these leaner starting points has been shown to have interesting and useful application in medicinal chemistry. Such efforts can provide excellent start points for renewed hit-to-lead campaigns while assisting medicinal chemists in gaining a deeper understanding on the ligandability of a protein. Selected case-studies making strategic use of the deconstruction–reconstruction logic are examined herein, thus aiming to highlight the value of employing this approach in drug discovery programs.