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November 20, 2014

Researchers create new AC inhibitor associated to melanoma, lung and prostate cancers

Researchers from UC Irvine School of Medicine and the Italian Institute of Technology have created a novel inhibitor compound for enzymes linked to melanoma, lung and prostate cancers.

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Researchers from UC Irvine School of Medicine and the Italian Institute of Technology have created a novel inhibitor compound for enzymes linked to melanoma, lung and prostate cancers.

The researchers described the first class of AC inhibitors that may aid in the efficacy of chemotherapies, in a chemistry journal Angewandte Chemie.

Encoded by the ASAH1 gene, acid ceramidase (AC) plays a crucial role in the regulation of cell fate and setting the balance between pro-aging / death and pro-life signals.

Mutations in the ASAH1 gene are said to be linked with a lysosomal storage disorder known as Farber disease and with spinal muscular atrophy.

UC Irvine anatomy and neurobiology professor Daniele Piomelli and colleagues presented a potent and systematically active small-molecule inhibitor of intracellular AC in their study.

"Encoded by the ASAH1 gene, acid ceramidase (AC) plays a crucial role in the regulation of cell fate and setting the balance between pro-aging / death and pro-life signals."

The researchers found that inhibiting AC with their novel compound tilts the balance between pro-aging / death and pro-life chemical signals, and favours the former at the expense of the latter, in the in vivo studies.

Piomelli said: "We hope that AC inhibitors may be one day used as ‘chemosensitisers’, drugs that enhance the cancer-killing power of anti-tumoural drugs.

"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."

The research was supported by the Carlsberg Foundation, while UC Irvine and the Fondazione Istituto Italiano di Tecnologia filed for patent protection of the new class of molecules.


Image: UC Irvine’s anatomy and neurobiology professor and Louise Turner Arnold chair in neurosciences Daniele Piomelli. Photo: courtesy of University of California , Irvine.

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