Target Validation Information
Target ID T40694
Target Name Serine/threonine-protein kinase PLK1
Target Type
Clinical Trial
Drug Potency against Target GSK461364 Drug Info IC50 = 2.2 nM [552961]
ON 019190.Na Drug Info IC50 = 30000 nM [537564]
BI 2536 Drug Info IC50 = 0.8 nM [552961]
Action against Disease Model BI 2536 Induced mitotic arrest and apoptosis (IC50 = 2-30 nM) in multiple t uMour cell lines; induced t uMour regression in h uMan colon carcinoma xenografts. [537564] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Plk3 activities were determined by immunochemistry and immunocomplex kinase assay approaches. Corneal epithelial wound healing was evaluated by a whole-eye organ culture model and by scratch-induced wound closure assay. Corneal epithelial layer was removed by using a corneal rust-ring-remover in wild-type and Plk3(-/-) mice. Wound healing was analyzed using a confocal imaging system. Cell growth was measured by MTT assays.The effect of hypoxic stress on early stages of corneal epithelial wound healing was compared with other oxidative stresses, including UV, CoCl(2), andH(2)O(2) treatments. Hypoxic stress-induced delay of corneal epithelial wound healing was further evaluated in h uMan corneal epithelial cells and in the corneas of wild-type and Plk3 knockout (Plk3(-/-)) mice. Hypoxic stress-induced Plk3 activation resulted in growth attenuation and delay of wound healing. Further evidence demonstrated that the increase in Plk3 activity in constitutively active Plk3-expressed cells significantly enhanced stress-induced delay of wound healing. In contrast, hypoxic stress-induced delay of wound healing was markedly diminished in the corneas of Plk3 deficient Plk3(-/-) mice.These results provide for the first time important evidence that Plk3 plays a significant role in hypoxic stress-induced attenuation of cell growth and delay of corneal epithelial wound healing [552961]
References
Ref 552961End of the line for cannabinoid receptor 1 as an anti-obesity target? An opinion. Nat Rev Drug Discov. 2009 Jul;8(7):594. doi: 10.1038/nrd2775-c1.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 537564Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Ref 552961End of the line for cannabinoid receptor 1 as an anti-obesity target? An opinion. Nat Rev Drug Discov. 2009 Jul;8(7):594. doi: 10.1038/nrd2775-c1.

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