Protein kinases as antibacterial targets.
The emergence of bacterial drug resistance highlights the need for new antibacterial targets. The role of protein kinases in signal transduction and cell regulation is ubiquitous. In spite of this the development of small molecule inhibitors of bacterial protein kinases has been slow, and no inhibitor has yet been successfully introduced to clinical use. In this review we focus on recent developments in inhibitors of the Histidine kinase family and pay particular attention to work on inhibiting the YycG Histidine kinase. We also highlight exciting new work in developing inhibitors for the eukaryote-like protein kinases of Mycobacterium tuberculosis including attempts to develop multi-target inhibitors.
Schreiber
Mark
M
Novartis Institute for Tropical Diseases, Singapore, Singapore. mark.schreiber@novartis.com
Res
Ivica
I
Matter
Alex
A
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D000071677:Histidine Kinase; D006801:Humans; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D000071677:Histidine Kinase