Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases was written by Apsel, Beth;Blair, Jimmy A.;Gonzalez, Beatriz;Nazif, Tamim M.;Feldman, Morri E.;Aizenstein, Brian;Hoffman, Randy;Williams, Roger L.;Shokat, Kevan M.;Knight, Zachary A.. And the article was included in Nature Chemical Biology in 2008.SDS of cas: 754214-56-7 This article mentions the following:
The clin. success of multitargeted kinase inhibitors has stimulated efforts to identify promiscuous drugs with optimal selectivity profiles. It remains unclear to what extent such drugs can be rationally designed, particularly for combinations of targets that are structurally divergent. Here we report the systematic discovery of mols. that potently inhibit both tyrosine kinases and phosphatidylinositol-3-OH kinases, two protein families that are among the most intensely pursued cancer drug targets. Through iterative chem. synthesis, X-ray crystallog. and kinome-level biochem. profiling, we identified compounds that inhibit a spectrum of new target combinations in these two families. Crystal structures revealed that the dual selectivity of these mols. is controlled by a hydrophobic pocket conserved in both enzyme classes and accessible through a rotatable bond in the drug skeleton. We show that compound I blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases. These mols. demonstrate the feasibility of accessing a chem. space that intersects two families of oncogenes. In the experiment, the researchers used many compounds, for example, 7-Azaindole-5-boronic Acid Pinacol Ester (cas: 754214-56-7SDS of cas: 754214-56-7).
7-Azaindole-5-boronic Acid Pinacol Ester (cas: 754214-56-7) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.SDS of cas: 754214-56-7
Referemce:
Indole alkaloid derivatives as building blocks of natural products from闂佽壈浜崹淇沜illus thuringiensis闂佽壈浜粋鍧闂佽壈浜崹淇沜illus velezensis闂佽壈浜粋鍧 their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles