3D‐chemocentric target deconvolution of unprecedented anti‐inflammatory drug scaffolds

Abstract

Background A typical hit‐to‐lead flow focuses on a well‐established molecular target. However, imperfect pathological backgrounds of the diseases can bring out low confidence on the chosen target. Therefore, despite unclear targets, the regulation of neuroinflammation is an important approach of early stage drug discovery in AD and neurological disorders. The potential targets of anti‐inflammatory agents are enormous but don't be clear investigated with their atomic level mechanism. Method ChOS (Chemistry‐oriented synthesis), a kind of inverse drug design, suggests target deconvolution of unprecedented anti‐inflammatory agents (in‐house compounds) through 3D‐chemocentric approach. Result The inverse approach identified an in‐house anti‐inflammatory agent, as the first‐in‐class small molecule antagonist for non‐histaminergic neurons, investigated a new therapeutic indication of a known target, and provided pharmacological profile of in‐house anti‐inflammatory agents. Conclusion The inverse drug discovery approach of in‐house anti‐inflammatory agents, ChOS, can be a compensatory alternative for neurological disorders and the results wait for AD & dementia collaboration.