p38 mitogen-activated protein (MAP) kinases are the serine/threonine protein kinases, which play a vital role in
cellular responses to external stress signals. p38 MAP kinase inhibitors have shown anti-inflammatory effects in the preclinical
disease models, primarily through inhibition of the expression of inflammatory mediators. A number of structurally
diverse p38 MAP kinase inhibitors have been developed as potential anti-inflammatory agents. Most of the inhibitors
have failed in the clinical trials either due to poor pharmacokinetic profile or selectivity issue, which makes p38 MAP
kinase a promising target for molecular modelling studies. Several quantitative structure activity relationships (QSAR)
and pharmacophore models have been developed to identify the structural requirements essential for p38 MAP kinase inhibitory
activity. In this review, we provide an overview of the presently known p38 MAP kinase inhibitors and how
QSAR analyses among series of compounds have led to the development of molecular models and pharmacophores, allowing
the design of novel inhibitors.
Keywords: CoMFA and CoMSIA, p38 MAP kinase, Pharmacophore modeling, QSAR, Virtual screening.
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