Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1368705 | Bioorganic & Medicinal Chemistry Letters | 2016 | 4 Pages |
Abstract
A series of selective TNNI3K inhibitors were developed by modifying the hinge-binding heterocycle of a previously reported dual TNNI3K/B-Raf inhibitor. The resulting quinazoline-containing compounds exhibit a large preference (up to 250-fold) for binding to TNNI3K versus B-Raf, are useful probes for elucidating the biological pathways associated with TNNI3K, and are leads for discovering novel cardiac medicines. GSK114 emerged as a leading inhibitor, displaying significant bias (40-fold) for TNNI3K over B-Raf, exceptional broad spectrum kinase selectivity, and adequate oral exposure to enable its use in cellular and in vivo studies.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Brian G. Lawhorn, Joanne Philp, Alan P. Graves, Lisa Shewchuk, Dennis A. Holt, Gregory J. Gatto Jr., Lara S. Kallander,