January 7, 2014

Development Of A Novel Dual JAK/Src Kinase Inhibitor

Inhibitors of both JAK and Src kinases represent promising targets for cancer therapeutics because of the central importance of these kinases in tumor cell proliferation and survival. Furthermore, in cancer cells activation of JAK has been reported as a compensatory effect in response to Src inhibitor exposure. This implies simultaneous inhibition of both kinases could have a synergy of anti-cancer effects compared to an agent that inhibits one or the other kinases.

The research article by Liu et al describes MLS-2384 which is a synthetic derivative of amarine natural product, 6-bromoindirubin-3′-oxime. MLS-2384 exhibits a dual JAK/Src kinase inhibitory activity, blocks downstream signaling into the STAT3 pathway, and has anti-cancer activity in various human cancer cell lines. These findings have important clinical implications for understanding the mechanisms of action of bromoindirubin derivatives.

The findings also indicate that this new 6-bromoindirubin derivative, MLS-2384, has potential as an anti-tumor therapeutic agent targeting JAK and Src kinases upstream of STAT3 in a wide variety of human cancer cells.


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