4i5m

Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein Phosphorylation in Rat Brain

spinqualitylabelsall models 4i5m, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4i5m is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: R78 Gene: PLK2, SNK (HUMAN) Activity: Polo kinase, with EC number 2.7.11.21 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of alpha-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology. Potent, selective, brain-penetrant inhibitors of Plk-2 were obtained from a structure-guided drug discovery approach driven by the first reported Plk-2-inhibitor complexes. The best of these compounds showed excellent isoform and kinome-wide selectivity, with physicochemical properties sufficient to interrogate the role of Plk-2 inhibition in vivo. One such compound significantly decreased phosphorylation of alpha-synuclein in rat brain upon oral administration and represents a useful probe for future studies of this therapeutic avenue toward the potential treatment of Parkinson's disease. Selective and Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors That Reduce alpha-Synuclein Phosphorylation in Rat Brain.,Aubele DL, Hom RK, Adler M, Galemmo RA Jr, Bowers S, Truong AP, Pan H, Beroza P, Neitz RJ, Yao N, Lin M, Tonn G, Zhang H, Bova MP, Ren Z, Tam D, Ruslim L, Baker J, Diep L, Fitzgerald K, Hoffman J, Motter R, Fauss D, Tanaka P, Dappen M, Jagodzinski J, Chan W, Konradi AW, Latimer L, Zhu YL, Sham HL, Anderson JP, Bergeron M, Artis DR ChemMedChem. 2013 Aug;8(8):1295-313. doi: 10.1002/cmdc.201300166. Epub 2013 Jun, 21. PMID:23794260 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase

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