6RK73 CAS# 1895050-66-4
6RK73 is a potent, selective, covalent, and irreversible inhibitor of ubiquitin C-terminal hydrolase L1 (UCHL1), an enzyme implicated in neurodegenerative diseases and cancer. In biochemical assays, 6RK73 inhibits recombinant UCHL1 with an IC₅₀ of 26 nM by covalently modifying the catalytic cysteine residue. It shows high selectivity over other deubiquitinases (DUBs), including UCHL3 and UCHL5, with >100-fold selectivity reported. In cell-based assays, 6RK73 effectively blocks UCHL1 activity at low micromolar concentrations, leading to accumulation of ubiquitinated proteins and perturbation of cellular ubiquitin homeostasis. Its irreversible covalent mechanism ensures sustained target engagement, making 6RK73 a valuable chemical probe for studying UCHL1’s role in protein degradation and neurobiology.
📌 参考资料/链接：
1.1Reagents:Cesium carbonateSolvents:Acetonitrile;5 min, rt1.22 h, rt2.1Solvents:Tetrahydrofuran;5 min, 0 °C2.2Reagents:Diisopropylethylamine,Propylphosphonic anhydrideSolvents:Ethyl acetate;0 °C; 1 h, rt3.1Reagents:Hydrochloric acidSolvents:Dichloromethane,Ethyl acetate;0 °C; 4 h, rt4.1Reagents:Potassium carbonateSolvents:Dichloromethane;0 °C; 16 h, rt
1.1Reagents:Cesium carbonateSolvents:Acetonitrile;5 min, rt1.22 h, rt2.1Solvents:Tetrahydrofuran;5 min, 0 °C2.2Reagents:Diisopropylethylamine,Propylphosphonic anhydrideSolvents:Ethyl acetate;0 °C; 1 h, rt3.1Reagents:Hydrochloric acidSolvents:Dichloromethane,Ethyl acetate;0 °C; 4 h, rt4.1Reagents:Potassium carbonateSolvents:Dichloromethane;0 °C; 16 h, rt
📄 详细内容
CAS No. 1895050-66-4 6RK73 synthetic routes
N-Heteroaryl cyanopyrrolidinecarboxamides as inhibitors of UCHL1 and their preparationAssignee: Mission Therapeutics Ltd.Inventors: Jones, Alison; et alWorld Intellectual Property OrganizationPatent#WO2016046530 A1
产品链接: CAS No. 1895050-66-4 ››
N-Heteroaryl cyanopyrrolidinecarboxamides as inhibitors of UCHL1 and their preparationAssignee: Mission Therapeutics Ltd.Inventors: Jones, Alison; et alWorld Intellectual Property OrganizationPatent#WO2016046530 A1
产品链接: CAS No. 1895050-66-4 ››