B-Raf Kinase V600E mutant in complex with a diarylthiazole B-Raf Inhibitor

Optimization of Diarylthiazole B-Raf Inhibitors: Identification of a Compound Endowed with High Oral Antitumor Activity, Mitigated Herg Inhibition, and Low Paradoxical Effect.

GPDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQL
AIVTQWCEGSSLYHHLHASETKFEMKKLIDIARQTARGMDYLHAKSIIHRDLKSNNIFLHEDNTVKIGDFGLATEKSRWS
GSHQFEQLSGSILWMAPEVIRMQDSNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIEMVGRGSLSPDLSKVRSNC
PKRMKRLMAECLKKKRDERPSFPRILAEIEELARELSG

0.1M HEPES PH 7.5.0, 0.2 M MGCL2 AND 20% PEG6000, VAPOR DIFFUSION, SITTING DROP

RESIDUES G446 P447 ARE EXPRESSION TAG RESIDUES I543A I544S I551K Q562R L588N V600E K630S F667E Y673S A688R L706S Q709R S713E L716E S720E P722S K723G ARE ENGINEERED MUTATION

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.