NT-0796

NT-0796 is an inhibitor of the NOD-like receptor protein 3 (NLRP3) inflammasome and a prodrug form of NDT-19795. It selectively inhibits NLRP3 over NLR family CARD domain-containing protein 4 (NLRC4) at 3 nM, as well as a panel of 121 other receptors at 10 µM, but does inhibit the serotonin (5-HT) receptor subtype 5-HT2B by 90% at 10 µM. NT-0796 inhibits LPS- and ATP-induced IL-1beta release in isolated human peripheral blood mononuclear cells (PBMCs) and whole blood (IC50s = 0.32 and 6.8 nM, respectively), however, it does not affect LPS-induced TNF-alpha or IL-6 release in isolated human PBMCs (IC50s = >2 µM for both), indicating NLRP3 selectivity. It decreases body weight, food intake, and plasma levels of total cholesterol, HDL, and proprotein convertase subtilisin kexin type 9 (PCSK9) in a model of high-fat diet-induced obesity using transgenic mice expressing human carboxylesterase-1 (CES1), the enzyme that converts NT-0796 to NDT-19795, when administered at a dose of 100 mg/kg three times per day.Formal Name: (alphaR)-alpha-[[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]oxy]-2-pyrimidinepropanoic acid, 1-methylethyl ester. CAS Number: 2272917-13-0. Molecular Formula: C23H27N3O4. Formula Weight: 409.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Slightly Soluble: 0.1-1 mg/ml, DMSO: Sparingly Soluble: 1-10 mg/ml. SMILES: O=C(NC1=C2CCCC2=CC3=C1CCC3)O[C@H](CC4=NC=CC=N4)C(OC(C)C)=O. InChi Code: InChI=1S/C23H27N3O4/c1-14(2)29-22(27)19(13-20-24-10-5-11-25-20)30-23(28)26-21-17-8-3-6-15(17)12-16-7-4-9-18(16)21/h5,10-12,14,19H,3-4,6-9,13H2,1-2H3,(H,26,28)/t19-/m1/s1. InChi Key: UMUQEMHROZVOTF-LJQANCHMSA-N.