Therapeutic targeting of HYPDH/PRODH2 with N-propargylglycine offers a Hyperoxaluria treatment opportunity

  • Biochim Biophys Acta Mol Basis Dis. 2024 Jan;1870(1):166848. doi: 10.1016/j.bbadis.2023.166848.
Joanna Bons  1 ,  Ada Tadeo  1 ,  Gary K Scott  1 ,  Fadzai Teramayi  1 ,  John J Tanner  2 ,  Birgit Schilling  1 ,  Christopher C Benz  1 ,  Lisa M Ellerby  3
Affiliations
  • 1. Buck Institute for Research on Aging, Novato, CA, USA.
  • 2. Departments of Biochemistry and Chemistry, University of Missouri, Columbia, MO, USA.
  • 3. Buck Institute for Research on Aging, Novato, CA, USA. Electronic address: [email protected].
PMID: 37586438 DOI: 10.1016/j.bbadis.2023.166848
Abstract

N-propargylglycine prevents 4-hydroxyproline catabolism in mouse liver and kidney. N-propargylglycine is a novel suicide inhibitor of PRODH2 and induces mitochondrial degradation of PRODH2. PRODH2 is selectively expressed in liver and kidney and contributes to primary hyperoxaluria (PH). Preclinical evaluation of N-propargylglycine efficacy as a new PH therapeutic is warranted.

Keywords
4-hydroxyproline (Hyp); 4-hydroxyproline dehydrogenase (HYPDH/PRODH2); N-propargylglycine (N-PPG); Primary hyperoxaluria (PH).
Products