1001333-93-2

Upstream product

• 109-83-1 (2-hydroxyethyl)(methyl)amine 
• 98-58-8 4-bromobenzenesulfonyl chloride 

Downstream Products

• 1311229-73-8 N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide 
• 1310948-05-0 4-bromo-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-N-methylbenzenesulfonamide 
• 1160931-29-2 C₁₅H₂₄BNO₅S 

Relevant academic research and scientific papers

Illuminating a Dark Kinase: Structure-Guided Design, Synthesis, and Evaluation of a Potent Nek1 Inhibitor and Its Effects on the Embryonic Zebrafish Pronephros

NIMA-related kinase 1 (Nek1) has lately garnered attention for its widespread function in ciliogenesis, apoptosis, and the DNA-damage response. Despite its involvement in various diseases and its potential as a cancer drug target, no directed medicinal chemistry efforts toward inhibitors against this dark kinase are published. Here, we report the structure-guided design of a potent small-molecule Nek1 inhibitor, starting from a scaffold identified by kinase cross-screening analysis. Seven lead compounds were identified in silico and evaluated for their inhibitory activity. The top compound, 10f, was further profiled for efficacy, toxicity, and bioavailability in a zebrafish polycystic kidney disease model. Administration of 10f caused the expansion of fluorescence-labeled proximal convoluted tubules, supporting our hypothesis that Nek1-inhibition causes cystic kidneys in zebrafish embryos. Compound 10f displayed insignificant inhibition in 48 of 50 kinases in a selectivity test panel. The findings provide a powerful tool to further elucidate the function and pharmacology of this neglected kinase.

2-PYRIDONE COMPOUNDS

A 2-pyridone compound represented by the formula [1]: {wherein in the formula [1], the ring represented by A represents a benzene ring or a pyridine ring, X represents any of the structures represented by the formulas [3] shown below: V represents a single bond or a lower alkylene group, and W represents a single bond, an ether bond or a lower alkylene group (wherein the lower alkylene group may contain an ether bond)}, a tautomer or stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is a compound that has an excellent GK activating effect and is useful as a pharmaceutical.