Kinase inhibitor profile for human Nek1, Nek6, and Nek7 and analysis of the structural basis for inhibitor specificity was written by Moraes, Eduardo Cruz;Meirelles, Gabriela Vaz;Honorato, Rodrigo Vargas;Brasil de Souza, Tatiana de Arruda Campos;Elisa de Souza, Edmarcia;Murakami, Mario Tyago;Lopes de Oliveira, Paulo Sergio;Kobarg, Jorg. And the article was included in Molecules in 2015.Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea This article mentions the following:
Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Δ262-1258)-(T162A), Isogranulatimide for hNek6(S206A), andGSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the resp. hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by mol. docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors. In the experiment, the researchers used many compounds, for example, 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea).
1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea (cas: 487021-52-3) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at δ 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Application In Synthesis of 1-(4-Methoxybenzyl)-3-(5-nitrothiazol-2-yl)urea
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica