A small molecule PTER-selective inhibitor reduces food intake and body weight - PubMed
a day ago
- #metabolic-regulation
- #obesity
- #enzyme-inhibitor
- PTER (phosphotriesterase-related) is an amidohydrolase involved in the catabolism of N-acetyltaurine, an anorexigenic metabolite.
- Crystal structures of eukaryotic PTER in apo and product-bound forms reveal an unexpected pocket homology with histone deacetylase (HDAC) enzymes.
- A substrate-competitive PTER inhibitor, PTERi, was engineered with nanomolar potency and >100-fold selectivity for PTER over HDACs.
- PTERi administration in diet-induced obese mice reduces food intake, enhances GLP1-RA-induced weight loss, and prevents weight regain after GLP1-RA discontinuation.
- The structural insights connect histone and metabolite deacetylation, providing a framework for pharmacological PTER inhibition in obesity.