High throughput screening for protein kinase inhibitors

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology and Drug Discovery

Background:

• Kinases play a crucial role in cell signaling and regulation, making them attractive targets for treating various diseases.
• The discovery of v-Src protein kinase in 1978 spurred extensive research into kinase modulators.
• Recent clinical successes of kinase inhibitors like Gleevec and Iressa have intensified interest in this drug class.

Purpose of the Study:

• To review the development of small molecule kinase inhibitors, primarily targeting the ATP binding pocket.
• To discuss strategies for selecting kinases as drug targets.
• To highlight lessons learned from ongoing kinase inhibitor development and examine high-throughput screening assay formats.

Main Methods:

• Focus on small molecule drugs, particularly inhibitors that bind to the ATP pocket.
• Review of general considerations for kinase target selection in drug discovery.
• Detailed description and discussion of high-throughput screening (HTS) assay formats.

Main Results:

• Kinase inhibitors have shown significant success in treating diseases like chronic myelogenous leukemia and non-small cell lung cancer.
• Small molecule modulators, often targeting the ATP binding site, are a major focus in drug development.
• Various assay formats are employed for high-throughput screening of potential kinase inhibitors.

Conclusions:

• Kinases represent a significant class of drug targets with demonstrated therapeutic potential.
• The development of orally available, low molecular weight kinase inhibitors is a key area of pharmaceutical research.
• Effective high-throughput screening methods are essential for identifying novel kinase-targeting drug candidates.