Apsel, Beth published the artcileTargeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases, Computed Properties of 1025707-92-9, the publication is Nature Chemical Biology (2008), 4(11), 691-699, database is CAplus and MEDLINE.
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.
Nature Chemical Biology published new progress about 1025707-92-9. 1025707-92-9 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Amide,Aldehyde,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is tert-Butyl 3-formyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate, and the molecular formula is C20H26BNO5, Computed Properties of 1025707-92-9.
Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles