4YHT

bRaf complexed with an inhibitor

Summary for 4YHT

• Entry DOI: 10.2210/pdb4yht/pdb
• Descriptor: Serine/threonine-protein kinase B-raf, GLYCEROL, 3-[(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-N-methyl-4-(morpholin-4-yl)benzenesulfonamide, ... (4 entities in total)
• Functional Keywords: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : P15056
• Total number of polymer chains: 2
• Total formula weight: 62987.36

Authors

Shewchuk, L.M.,Lawhorn, B.G. (deposition date: 2015-02-27, release date: 2016-03-16, Last modification date: 2024-02-28)

Primary citation

Lawhorn, B.G.,Philp, J.,Graves, A.P.,Shewchuk, L.,Holt, D.A.,Gatto, G.J.,Kallander, L.S.
GSK114: A selective inhibitor for elucidating the biological role of TNNI3K.
Bioorg.Med.Chem.Lett., 26:3355-3358, 2016

PubMed 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.

PubMed: 27246618
DOI: 10.1016/j.bmcl.2016.05.033

Experimental method

X-RAY DIFFRACTION (3.05 Å)