LEI-106 

LEI-106 is a dual ABHD6 and DAGL-α inhibitor, with a K_i of 0.8 μM for ABHD6, and an IC₅₀ of 18 nM and a K_i of 0.7 μM for DAGL-α. LEI-106 blocks the synthesis of 2-arachidonoylglycerol, reduces the level of endothelial cell-derived 2-arachidonoylglycerol, without altering the levels of cannabinoids and diacylglycerol. LEI-106 is applicable to research related to diet-induced obesity and metabolic syndrome^[1][2].

LEI-106 (compound 15) potently inhibits human DAGL-α activity in cell-free HEK293 membranes, with an IC₅₀ of 18 nM in a colorimetric assay and a K_i of 0.7 μM against the natural substrate^[1].
LEI-106 (20 μM; 20 min) potently inhibits endogenous DAGL-α activity in mouse brain membrane homogenates, with an IC₅₀ of 124 nM, and also acts as an inhibitor of ABHD6 in this system^[1].
LEI-106 (30 min) potently inhibits human ABHD6 activity in cell-free HEK293T membranes, with a K_i of 0.8 μM against the natural substrate 2-AG^[1].
LEI-106 (1.3 mM; 15 min) significantly reduces 2-AG levels in bEnd.3 mouse brain endothelial cells without altering AEA levels^[2].
LEI-106 (650 μM-1.3 mM; 15 min) significantly increases PKC activity in bEnd.3 mouse brain endothelial cells^[2].
LEI-106 (650 μM-1.3 mM; 15 min) induces VE-cadherin fragmentation in bEnd.3 mouse brain endothelial cells, with the 1.3 mM concentration also reducing full-length VE-cadherin, claudin-5, and ZO-1 levels; VE-cadherin fragmentation is mitigated by Rho-kinase inhibition but not calpain or PKC inhibition^[2].
LEI-106 (650-1.3 mM; 2 min) significantly increases intracellular calcium levels in bEnd.3 mouse brain endothelial cells^[2].
LEI-106 (650 μM; 15 min) significantly alters the phospho-proteome of bEnd.3 mouse brain endothelial cells, with changes in pathways related to mRNA processing, cytoskeletal organization, and Rho GTPase signaling^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

481.56

C₂₆H₂₇NO₆S

1620582-23-1

Solid

White to off-white

OC(CN(CC1=CC=C(OC2=CC=CC=C2)C=C1)S(C3=CC=C4OC(C)(CCC4=C3)C)(=O)=O)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Janssen FJ, et al. Discovery of glycine sulfonamides as dual inhibitors of sn-1-diacylglycerol lipase α and α/β-hydrolase domain 6. J Med Chem. 2014;57(15):6610-6622.  [Content Brief]

  [2]. Levine AA, et al. Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome. Int J Mol Sci. 2023;25(1):531. Published 2023 Dec 30.  [Content Brief]