NT-0796 is an orally active, selective and CNS-penetrant NLRP3 inflammasome inhibitor. NT-0796 inhibits IL-1β release in human PBMC cells with an IC50 value of 0.32 nM. NT-0796 is an isopropyl ester that undergoes intracellular conversion to NDT-19795, the carboxylic acid active species. NT-0796 reverses high fat diet-induced obesity, systemic inflammation and astrogliosis in the diet-induced obesity mouse model. NT-0796 is promising for research of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis[1][2][3][4].
References:
[1]. David Harrison, et al. Discovery of Clinical Candidate NT-0796, a Brain-Penetrant and Highly Potent NLRP3 Inflammasome Inhibitor for Neuroinflammatory Disorders. J Med Chem. 2023 Oct 24.
[2]. Thornton P, et al. Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796. J Pharmacol Exp Ther. 2024 Feb 15;388(3):813-826.
[3]. Smolak P, et al. Target Cell Activation of a Structurally Novel NOD-Like Receptor Pyrin Domain-Containing Protein 3 Inhibitor NT-0796 Enhances Potency. J Pharmacol Exp Ther. 2024 Feb 15;388(3):798-812.
[4]. Doedens JR, et al. The ester-containing prodrug NT-0796 enhances delivery of the NLRP3 inflammasome inhibitor NDT-19795 to monocytic cells expressing carboxylesterase-1. Biochem Pharmacol. 2024 Sep;227:116455.