| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T88318 | ||||
| Target Name | Protein kinase C | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | Rottlerin | Drug Info | IC50 = 3000 nM | [553213] | |
| Action against Disease Model | Rottlerin | Rottlerin could inhibit the phosphorylation of PKCdelta and attenuate 6-OHDA-induced cell death, and the cell viability was raised to (69.6+/-2.63)% of that in control group (P<0.05). In contrast, PMA induced a significant increase in PKCdelta phosphorylation and also strengthened the cytotoxic effects of 6-OHDA. The cell viability of PMA-treated PC12 cells decreased to (49.8+/-5.06)% of that in control group (P<0.001). Rottlerin can protect PC12 cells from cytotoxicity of 6-OHDA probably by inhibiting PKCdelta phosphorylation. The results suggest that PKCdelta may be a key regulator of neuron loss in Parkinson's disease. | [552964] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | The members of Protein Kinase C (PKC) family are serine threonine kinases, abundantly expressed in cells that maintain cardiovascular health. Studies done using pharmacological tools that block wide range of PKCs or specific PKC isoforms and PKC gene knockout animals revealed that these enzymes regulate critical functional responses in cardiovascular cells. Interestingly, PKC isotype activity is context specific and PKC isotypes may have opposing functional roles depending on cell type and cellular environment (eg., cardiomyocytes, platelets). Furthermore, precise structural differences that occur amongst these isoforms have lead to development of compounds that inhibit or activate specific PKC isoforms. Thus, it is feasible to enhance the protective effects of a PKCisoform, while minimizing the damage caused by other members of PKC family. | [553213] | |||
| References | |||||
| Ref 553213 | Rottlerin, a novel protein kinase inhibitor. Biochem Biophys Res Commun. 1994 Feb 28;199(1):93-8. | ||||
| Ref 552964 | Rottlerin protected dopaminergic cell line from cytotoxicity of 6-hydroxydopamine by inhibiting PKCdelta phosphorylation. Neurosci Bull. 2009 Aug;25(4):187-95. | ||||
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