AC, which is encoded by the ASAH1 gene, plays an important role in the regulation of cell fate, setting the balance between pro-aging/death and pro-life signals. Mutations in the ASAH1 gene have been associated with a lysosomal storage disorder called Farber disease and with spinal muscular atrophy.
In their Angewandte Chemie study, UC Irvine’s Daniele Piomelli — the Louise Turner Arnold Chair in the Neurosciences — and colleagues present a potent and systematically active small-molecule inhibitor of intracellular AC.
In in vivo studies, the team found that inhibiting AC with their novel compound tilts the balance between pro-aging/death and pro-life chemical signals, favoring the former at the expense of the latter.
“We hope that AC inhibitors may be one day used as ‘chemosensitizers’ — drugs that enhance the cancer-killing power of anti-tumoral drugs,” said Piomelli, a professor in the Department of Anatomy Neurobiology who also is affiliated with UC Irvine Chao Family Comprehensive Cancer Center.
“The new chemical scaffold we published is a promising starting point for the development of novel therapeutic agents, and we aim to pursue its further pharmaceutical development.”