BENGALURU: Three groups from scientists from IISc — K Durga Prasad and Prof T N Guru Row from Solid State and Structural Chemistry Unit, J Trinath and Prof K N Balaji from MCBL and Anshuman Biswas and Prof K Sekar from Bioinformatics — have worked on chemical modification of the commercially available and expensive stress-activated protein JNK inhibitor SP600125 to help treatment of disorders caused due to sepsis.
The modification improves the inhibitor’s ability to bind and limit JNK at very low concentrations. It also reduces the expression of the inflammatory genes which lead to septic shock. “Our study is among the first reports of the description and meticulous biochemical characterisation of selective JNK inhibitors,” says Professor Balaji K N.
This selective and more efficient inhibition activity of JNK inhibitors could facilitate the generation of novel therapeutics to treat sepsis and other inflammatory disorders. The paper appeared in the journal ‘Scientific Reports’ in November 2014.
Sepsis is a rising cause of mortality across the world. It is caused by uncontrolled expression of several inflammatory genes in the host, leading to irreparable damage.
The sudden onset and excessive expression of these genes leads to the accumulation of harmful metabolic end products, resulting in multiple organ failure. During such cellular stress, some proteins are activated.
The stress-activated proteins comprise of two main subsets - c-Jun N-terminal Kinase (JNK) and p38 Mitogen Activated Protein Kinase (MAPK).