Illuminating a Dark Kinase: Structure-Guided Design, Synthesis, and Evaluation of a Potent Nek1 Inhibitor and Its Effects on the Embryonic Zebrafish Pronephros was written by Baumann, Georg;Meckel, Tobias;Boehm, Kevin;Shih, Yung-Hsin;Dickhaut, Mirco;Reichardt, Torben;Pilakowski, Johannes;Pehl, Ulrich;Schmidt, Boris. And the article was included in Journal of Medicinal Chemistry in 2022.HPLC of Formula: 109-85-3 The following contents are mentioned in the article:
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 chem. efforts toward inhibitors against this dark kinase are published. Here, we report the structure-guided design of a potent small-mol. Nek1 inhibitor, starting from a scaffold identified by kinase cross-screening anal. 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 pharmacol. of this neglected kinase. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3HPLC of Formula: 109-85-3).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.HPLC of Formula: 109-85-3
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem