Medical Significance
CDKs are considered a potential target for anti-cancer medication. If it is possible to selectively interrupt the cell cycle regulation in cancer cells by interfering with CDK action, the cell will die. At present, some CDK inhibitors such as Seliciclib are undergoing clinical trials. Although it was originally developed as a potential anti-cancer drug, in recent laboratory tests Seliciclib has also proven to induce apoptosis in neutrophil granulocytes, which mediate inflammation. This means that novel drugs for treatment of chronic inflammation diseases such as arthritis and cystic fibrosis could be developed.
Flavopiridol (Alvocidib) is the first CDK inhibitor to be tested in clinical trials after being identified in an anti-cancer agent screen in 1992. It competes for the ATP site of the CDKs.
More research is required, however, because disruption of the CDK-mediated pathway has potentially serious consequences; while CDK inhibitors seem promising, it has to be determined how side-effects can be limited so that only target cells are affected. As such diseases are currently treated with glucocorticoids, which have often serious side-effects, even a minor success would be an improvement.
Complications of developing a CDK drug include the fact that many CDKs are not involved in the cell cycle such as transcription, viral infection, neural physiology, and glucose homeostatsis.
Table 4: Cyclin-dependent kinase inhibitor drugs
| Drug | CDKs Inhibited |
|---|---|
| Flavopiridol (Alvocidib) | 1, 2, 4, 6, 7, 9 |
| Olomoucine | 1, 2, 5 |
| Roscovitine | 1, 2, 5 |
| Purvalanol | 1, 2, 5 |
| Paullones | 1, 2, 5 |
| Butryolactone | 1, 2, 5 |
| Thio/oxoflavopiridols | 1 |
| Oxindoles | 2 |
| Aminothiazoles | 4 |
| Benzocarbazoles | 4 |
| Pyrimidines | 4 |
| Seliciclib | ? |
Read more about this topic: Cyclin-dependent Kinase
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