4I5M: Selective & Brain-permeable Polo-like Kinase-2 (plk-2) Inhibitors That Reduce -synuclein Phosphorylation In Rat Brain

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.
PDB ID: 4I5MDownload
MMDB ID: 116226
PDB Deposition Date: 2012/11/28
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4I5M: monomeric; determined by author and by software (PISA)
Molecular Components in 4I5M
Label Count Molecule
Protein (1 molecule)
Serine/threonine-protein Kinase Plk2(Gene symbol: PLK2)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB