Structure of PDB 4ctc Chain A Binding Site BS01

Receptor Information
>4ctc Chain A (length=288) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
PNYCFAGKTSSISDLKEVPRKNITLIRGLGGEVYEGQVPLQVAVKTLPEV
CSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLK
SFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNC
LLTCPGPGRVAKIGDFGMARDIGGCAMLPVKWMPPEAFMEGIFTSKTDTW
SFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMT
QCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEY
Ligand information
Ligand IDJ99
InChIInChI=1S/C23H24FN5O2/c1-12-17-9-15(24)6-7-16(17)23(30)28(2)11-18-20(21(13-4-5-13)27-29(18)3)14-8-19(31-12)22(25)26-10-14/h6-10,12-13H,4-5,11H2,1-3H3,(H2,25,26)/t12-/m1/s1
InChIKeySBEYSILWLYDNSN-GFCCVEGCSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC1c2cc(ccc2C(=O)N(Cc3c(c(nn3C)C4CC4)-c5cc(c(nc5)N)O1)C)F
OpenEye OEToolkits 1.7.6C[C@@H]1c2cc(ccc2C(=O)N(Cc3c(c(nn3C)C4CC4)-c5cc(c(nc5)N)O1)C)F
ACDLabs 12.01Fc3ccc2C(=O)N(Cc1n(nc(c1c4cc(OC(c2c3)C)c(nc4)N)C5CC5)C)C
CACTVS 3.385C[C@H]1Oc2cc(cnc2N)c3c(CN(C)C(=O)c4ccc(F)cc14)n(C)nc3C5CC5
CACTVS 3.385C[CH]1Oc2cc(cnc2N)c3c(CN(C)C(=O)c4ccc(F)cc14)n(C)nc3C5CC5
FormulaC23 H24 F N5 O2
Name(10R)-7-amino-3-cyclopropyl-12-fluoro-1,10,16-trimethyl-16,17-dihydro-1H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecin-15(10H)-one
ChEMBLCHEMBL3286829
DrugBank
ZINCZINC000098209037
PDB chain4ctc Chain A Residue 2402 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4ctc 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.
Resolution2.03 Å
Binding residue
(original residue number in PDB)		L1122 V1130 A1148 E1197 M1199 A1200 N1254 L1256 G1269 D1270 Y1401
Binding residue
(residue number reindexed from 1)		L29 V33 A43 E92 M94 A95 N149 L151 G164 D165 Y288
Annotation score1
Binding affinityBindingDB: IC50=5.8nM,Ki=<0.100000nM
Enzymatic activity
Catalytic site (original residue number in PDB) D1249 A1251 R1253 N1254 D1270
Catalytic site (residue number reindexed from 1) D144 A146 R148 N149 D165
Enzyme Commision number 2.7.10.1: receptor protein-tyrosine kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005524 ATP binding
Biological Process
GO:0006468 protein phosphorylation
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
Cellular Component
GO:0016020 membrane

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4ctc, PDBe:4ctc, PDBj:4ctc
PDBsum4ctc
PubMed24819116
UniProtQ9UM73|ALK_HUMAN ALK tyrosine kinase receptor (Gene Name=ALK)

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