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3D‐chemocentric target deconvolution of unprecedented anti‐inflammatory drug scaffolds
Author(s) -
Kim Mihyun,
Dhorma Lama Prema,
Teli Mahesh Kumar,
Venkanna Arramshetti
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043054
Subject(s) - neuroinflammation , drug , drug discovery , dementia , neuroscience , deconvolution , pharmacology , drug target , medicine , inflammatory response , inflammation , computational biology , computer science , bioinformatics , psychology , biology , immunology , disease , algorithm
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.