Structure of the Human Anaplastic Lymphoma Kinase in Complex with the inhibitor 3-((1R)-1-(5-fluoro-2-methoxyphenyl)ethoxy)-5-(1-methyl-1H- 1,2,3-triazol-5-yl)pyridin-2-amine

Discovery of (10R)-7-Amino-12-Fluoro-2,10,16-Trimethyl-15-Oxo-10,15,16,17-Tetrahydro-2H-8,4-(Metheno)Pyrazolo[4,3-H][2,5,11]Benzoxadiazacyclotetradecine-3-Carbonitrile (Pf-06463922), a Macrocyclic Inhibitor of Alk/Ros1 with Pre-Clinical Brain Exposure and Broad Spectrum Potency Against Alk-Resistant Mutations.

TYROSINE KINASE DOMAIN, RESIDUES 1093-1411

ANAPLASTIC LYMPHOMA KINASE, ANAPLASTIC LYMPHOMA KINASE

MAHHHHHHNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDF
LMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENH
FIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFS
LGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPL
VEEEEKV

HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 13-15 MG/ML)CONTAINING 0.001M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION CONTAINING: 0.15M AMMONIUM SULFATE, 9-10.5% MONOMETHYLETHER PEG5K AND 0.1M MES IN THE PH RANGE 5.3-6.5.

STRUCTURE OF THE HUMAN ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH THE INHIBITOR 2-((1R)-1-((3-AMINO-6-( 2-METHOXYPYRIDIN-3-YL)PYRAZIN-2-YL)OXY)ETHYL)-4- FLUORO-N-METHYLBENZAMIDE

STRUCTURE OF THE HUMAN ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH THE INHIBITOR 3-((1R)-1-(5-FLUORO-2-( 2H-1,2,3-TRIAZOL-2-YL)PHENYL)ETHOXY)-5-(3-( METHYLSULFONYL)PHENYL)PYRIDIN-2-AMINE

STRUCTURE OF THE HUMAN ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH THE INHIBITOR (10R)-7-AMINO-12-FLUORO-1 ,3,10,16-TETRAMETHYL-16,17-DIHYDRO-1H-8,4-( METHENO)PYRAZOLO(4,3-H)(2,5,11) BENZOXADIAZACYCLOTETRADECIN-15(10H)-ONE

TRANSFERASE, RECEPTOR TYROSINE KINASE, INHIBITOR