Pollack, Scott J.; Beyer, Kim S.; Lock, Christopher; Mueller, Ilka; Sheppard, David; Lipkin, Mike; Hardick, David; Blurton, Peter; Leonard, Philip M.; Hubbard, Paul A.; Todd, Daniel; Richardson, Christine M.; Ahrens, Thomas; Baader, Manuel; Hafenbradl, Doris O.; Hilyard, Kate; Buerli, Roland W. published an article in Journal of Computer-Aided Molecular Design. The title of the article was 《A comparative study of fragment screening methods on the p38α kinase: new methods, new insights》.Synthetic Route of C11H13N3OS The author mentioned the following in the article:
The stress-activated kinase p38α was used to evaluate a fragment-based drug discovery approach using the BioFocus fragment library. Compounds were screened by surface plasmon resonance (SPR) on a Biacore T100 against p38α and two selectivity targets. A sub-set of the library was the focus of detailed follow-up analyses that included hit confirmation, affinity determination on 24 confirmed, selective hits and competition assays of these hits with respect to a known ATP binding site inhibitor. In addition, functional activity against p38α was assessed in a biochem. assay using a mobility shift platform (LC3000, Caliper LifeSciences). A selection of fragments was also evaluated using fluorescence lifetime (FLEXYTE) and microscale thermophoresis (Nanotemper) technologies. A good correlation between the data for the different assays was found. Crystal structures were solved for four of the small mols. complexed to p38α. Interestingly, as determined both by X-ray anal. and SPR competition experiments, three of the complexes involved the fragment at the ATP binding site, while the fourth compound bound in a distal site that may offer potential as a novel drug target site. A first round of optimization around the remotely bound fragment has led to the identification of a series of triazole-containing compounds This approach could form the basis for developing novel and active p38α inhibitors. More broadly, it illustrates the power of combining a range of biophys. and biochem. techniques to the discovery of fragments that facilitate the development of novel modulators of kinase and other drug targets.6-Morpholinobenzo[d]thiazol-2-amine(cas: 94641-22-2Synthetic Route of C11H13N3OS) was used in this study.
6-Morpholinobenzo[d]thiazol-2-amine(cas: 94641-22-2) belongs to thiazoles. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities.Synthetic Route of C11H13N3OSTheir presence in peptides or their ability to bind proteins, DNA and RNA has led to many synthetic studies and new applications.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica