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Figure 2 | Journal of Neuroinflammation

Figure 2

From: A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

Figure 2

Design of MW01-2-069A-SRM. A) Pharmacophore model showing the potential for 069A to make selective interactions in the active site of p38α MAPK. The pyridine ring nitrogen has the potential to make the critical interaction with the hydrogen of the amide bond formed between Met109 and Gly110. This interaction and the potential to occupy the nearby hydrophobic pocket are important interactions for p38α MAPK selective inhibitors. The "gatekeeper residue" in p38α and p38β is Thr106. Its small size compared to the larger Met in p38δ and p38γ isoforms allows bulkier groups in the compound to access the pocket, thereby providing isoform selectivity and potential affinity. B) Amino acid sequence alignment of p38 MAPK isoforms in the region containing key amino acids implicated in selective kinase-inhibitor interactions.

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Journal of Neuroinflammation

ISSN: 1742-2094