Taipale, Mikko published the artcileChaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells, Name: SU6656, the publication is Nature Biotechnology (2013), 31(7), 630-637, database is CAplus and MEDLINE.
The interaction between the HSP90 chaperone and its client kinases is sensitive to the conformational status of the kinase, and stabilization of the kinase fold by small mols. strongly decreases chaperone interaction. Here we exploit this observation and assay small-mol. binding to kinases in living cells, using chaperones as ‘thermodn. sensors’. The method allows determination of target specificities of both ATP-competitive and allosteric inhibitors in the kinases’ native cellular context in high throughput. We profile target specificities of 30 diverse kinase inhibitors against >300 kinases. Demonstrating the value of the assay, we identify ETV6-NTRK3 as a target of the FDA-approved drug crizotinib (Xalkori). Crizotinib inhibits proliferation of ETV6-NTRK3-dependent tumor cells with nanomolar potency and induces the regression of established tumor xenografts in mice. Finally, we show that our approach is applicable to other chaperone and target classes by assaying HSP70/steroid hormone receptor and CDC37/kinase interactions, suggesting that chaperone interactions will have broad application in detecting drug-target interactions in vivo.
Nature Biotechnology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C28H18O4, Name: SU6656.
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