Synonyms: (4-([1,1'-Biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone
Molecular Formula: C27H26N4O
Molecular Weight: 422.52
Linear Structural Formula: C27H26N4O
Purity: >=98% (HPLC)
Storage: 2-8C
Biochem Physiol Actions: KT109 is a potent and selective inhibitor of Diacylglycerol lipase DAGLbeta. Diacylglycerol lipases DAGLalpha and DAGLbeta are serine hydrolases that biosynthesize the endocannabinoid 2-arachidonoylglycerol (2-AG). A lack of selective inhibitors has hampered study of these lipases. KT109 is a potent and selective DAGLbeta inhibitor with an IC50 of 42 nM, ~60-fold selectivity for DAGLbeta over DAGLalpha, and negligible activity against FAAH, MGLL and ABHD11, other key enzymes involved in endocannabinoid signaling. KT109 shows some inhibitory activity against PLA2G7 (IC50 = 1 muM) but no inhibitory activity against cytosolic phospholipase A2 (cPLA2 or PLA2G4A). The main off target inhibition against ABHD6 (IC50 = 16 nM) can be controlled for by use of the related compound, KT195, a potent (IC50 = 10 nM) and selective ABHD6 inhibitor with negligible activity against DAGLbeta. KT109 disrupts the lipid network involved in macrophage inflammatory responses, lowering 2-AG, as well as arachidonic acid and eicosanoids, in mouse peritoneal macrophages.