Development of Selective Clk1 and -4 Inhibitors for Cellular Depletion of Cancer-Relevant Proteins was written by ElHady, Ahmed K.;Abdel-Halim, Mohammad;Abadi, Ashraf H.;Engel, Matthias. And the article was included in Journal of Medicinal Chemistry in 2017.Category: imidazoles-derivatives This article mentions the following:
In cancer cells, kinases of the Clk family control the supply of full-length, functional mRNAs coding for a variety of proteins essential to cell growth and survival. Thus, inhibition of Clks might become a novel anticancer strategy, leading to a selective depletion of cancer-relevant proteins after turnover. On the basis of a Weinreb amide hit compound, the authors designed and synthesized a diverse set of methoxybenzothiophene-2-carboxamides, of which the N-benzylated derivative showed enhanced Clk1 inhibitory activity. Introduction of a m-fluorine in the benzyl moiety eventually led to the discovery of compound 21b (5-methoxybenzo[b]thiophene-2-carboxylic acid (3-fluorobenzyl)methylamide), a potent inhibitor of Clk1 and -4 (IC50 = 7 and 2.3 nM, resp.), exhibiting an unprecedented selectivity over Dyrk1A. Compound 21b triggered the depletion of EGFR, HDAC1, and p70S6 kinase from the cancer cells, with potencies in line with the measured GIC50 values. In contrast, the cellular effects of congener 21a (5-methoxybenzo[b]thiophene-2-carboxylic acid 3-fluorobenzylamide), which inhibited Clk1 only weakly, were substantially lower. In the experiment, the researchers used many compounds, for example, (1H-Imidazol-2-yl)methanamine dihydrochloride (cas: 22600-77-7Category: imidazoles-derivatives).
(1H-Imidazol-2-yl)methanamine dihydrochloride (cas: 22600-77-7) belongs to imidazole derivatives. Imidazole derivatives generally have good solubility in protic solvents. Simple imidazole derivatives, such as 1H-imidazole, 2-methyl-1H-imidazole, and 1,2-dimethylimidazole, have very high solubility in water. Imidazole based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Category: imidazoles-derivatives
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem