Abstract:
:Inhibition of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signalling cascade, may represent a novel treatment for allergic asthma. Here we report the structure-based optimization of a series of benzothiazole amides that demonstrate sub-nanomolar inhibitory potency against ITK with good cellular activity and kinase selectivity. We also elucidate the binding mode of these inhibitors by solving the X-ray crystal structures of several inhibitor-ITK complexes.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
MacKinnon CH,Lau K,Burch JD,Chen Y,Dines J,Ding X,Eigenbrot C,Heifetz A,Jaochico A,Johnson A,Kraemer J,Kruger S,Krülle TM,Liimatta M,Ly J,Maghames R,Montalbetti CA,Ortwine DF,Pérez-Fuertes Y,Shia S,Stein DB,Trandoi
10.1016/j.bmcl.2013.09.069subject
Has Abstractpub_date
2013-12-01 00:00:00pages
6331-5issue
23eissn
0960-894Xissn
1464-3405pii
S0960-894X(13)01143-8journal_volume
23pub_type
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