Candidate Drug Blocks Enzyme Activity in Pancreatic and Lung Cancer Cells

Cancer researchers have identified a candidate drug that blocks the activity of the serine/threonine-protein kinase TBK1 (TANK-binding kinase 1), an enzyme overexpressed in some pancreatic and non-small-cell lung cancers.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) screened more than 250,000 compounds while searching for any that could inhibit this enzyme and eliminate the survival advantage that it gives to cancer cells through its activation of Akt, a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription, and cell migration.

A paper published in the February 18, 2011, issue of the journal Molecular Cell identified the potential drug as 6-aminopyrazolopyrimidine, a compound that had been developed in collaboration with the pharmaceutical company Amgen (Thousand Oaks, CA, USA). This compound blocked the effects of TBK1 in 40% to 50% of the non-small-cell lung cancer and pancreatic cancer tissue cultures tested.

"Our prediction is that TBK1 is a good pharmacological intervention target for a subset of lung and pancreas cancers that are addicted to the activity of this enzyme. We believe there is a large population of cancer patients that could respond to inhibition of this activity,” said senior author Dr. Michael White, professor of cell biology at the University of Texas Southwestern Medical School.

"We found a biological activity that some cancer cells need to be able to survive, and we found a way to turn it off,” said Dr. White.

Related Links:
University of Texas Southwestern Medical Center
Amgen