| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1371457 | Bioorganic & Medicinal Chemistry Letters | 2011 | 5 Pages |
Abstract
Based on a hit cluster of compounds inhibiting interleukin-2 inducible T-cell kinase (ITK) in the submicromolar range a series of ITK inhibitor libraries were synthesized. Through iterative design cycles including kinase crystal structure information, indolylindazole libraries were identified which showed low nanomolar activity in enzymatic and cellular assays. The potential of these novel lead series was confirmed through in vivo tests in an anti-CD3-IL2 mouse model. The intravenous administration of highly potent ITK inhibitor 11o resulted in dose-dependent, efficient suppression of IL-2.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Matthias Herdemann, Alexander Weber, Jérôme Jonveaux, Frank Schwoebel, Michael Stoeck, Isabelle Heit,