Novel Small-Molecule Integrin-linked Kinase/Phosphoinositide-dependent Protein Kinase-2 Inhibitors
T2011-050 A novel set of molecules that inhibit integrin-linked kinase in order to suppress tumor cell growth and metastasis.
The Akt signaling pathway is responsible for apoptosis, cell proliferation, and metabolism. In tumor cells, this pathway is up-regulated and aids in promoting cancer cell survival. Complete activation of Akt pathway requires phosphorylation at two amino-acid residues, which are phosporylated by separate kinases at two sites (referenced as PDK 1 and 2). THe novel compounds described herein target PDK2, and focus on the integrin-linked kinase (ILK) as a mode of suppression. An increase in ILK expression and activity has been linked with various cancer types. Suppression of ILK can lead to inhibition of cancer cell survival through an induction of apoptosis. The development of novel, potent, and safe inhibitors of ILK could provide new targeted therapeutics for the treatment of cancer.
The Ohio State University researchers, led by Dr. Ching-Shih Chen, have discovered a family of novel compounds that exhibit superior potencies for the inhibition of tumor cell growth and metastasis. The compounds were specifically chosen to have the highest efficacy in tumor suppression. Experimental results have proven the concept and mechanism by which the treatment operates.
- Cancer therapeutics
- The molecule inhibitors have the potential to suppress tumor metabolism and cell proliferation within tumors and exhibit a higher rate of apoptosis
- The compounds exhibit greater in vitro and in vivo potencies than other published small-molecule inhibitors of ILK