Druggability Assessment of Targets Used in Kinetic Target-Guided Synthesis

J Med Chem. 2018 Nov 8;61(21):9395-9409. doi: 10.1021/acs.jmedchem.8b00266. Epub 2018 Jun 27.

Abstract

Kinetic target-guided synthesis (KTGS) is a powerful strategy in which the biological target selects its own inhibitors by assembling them from biocompatible reagents via an irreversible process. In this approach, the biological target accelerates the reaction between complementary building blocks by bringing them in close proximity and proper orientation. KTGS has found application on various targets. Herein, we performed a druggability assessment for each target family reported in KTGS, calculated the pocket properties, and used them to extract possible discriminating factors for successful KTGS studies. A trend for less enclosed pockets emerged, but overall we conclude that the KTGS approach is universal and could be used without restrictions regarding the physicochemical properties of the addressed pocket.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Discovery / methods*
  • Humans
  • Kinetics
  • Molecular Targeted Therapy / methods*