Inhibition of Aminoacylase 3 (Aa3) in the Treatment of Cancer

UCLA researchers have developed Ras pathway inhibitors with anti-proliferative effects in HCC cell models. Ras proteins require translocation and insertion into the plasma membrane to function, a process that is mediated by post-translational prenylation of Ras proteins. The rate of prenylation is regulated by the biosynthesis and regeneration of prenyl moiety precursors. Normal regeneration of the prenyl moiety is controlled by N-acetylation of precursors. It has also been uncovered that elevated levels of aminoacylase 3 (AA3) in HCC cells compared to healthy cells may be responsible for increased deacetylation of prenyl group precursors leading to increased Ras prenylation and subsequent activation HCC cell proliferation. Inhibition of AA3 with novel compounds was shown to significantly decrease membrane bound Ras and reduce cell viability in multiple HCC cell lines with little to no effect on normal hepatocytes. Initial results are promising for the adaption of AA3 inhibition to address the unmet therapeutic needs of HCC and Ras driven cancers.

Abstract

UCLA researchers have developed aminoacylase 3 (AA3) inhibitors to treat hepatocellular carcinoma (HCC) and other Ras driven cancers.

Website

https://techtransfer.universityofcalifornia.edu/NCD/24938.html?utm_source=AUTMGTP&utm_medium=webpage&utm_term=ncdid_24938&utm_campaign=TechWebsites

Advantages

  • AA3 inhibitors stop cell proliferation and are toxic specifically to HCC cells and not normal hepatocytes.

Potential Applications

  • AA3 inhibitors can be developed into a therapeutic against HCC or other Ras driven cancers. 

Contact Information

Name: UCLA Technology Development Group

Email: ncd@tdg.ucla.edu

Phone: 310.794.0558