Target Binding Site Detail

Content Navigation (  All   None )                                      
Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T90989 Target Info
Target Name Fibroblast growth factor receptor 4 (FGFR4)
Synonyms TKF; JTK2; FGFR-4; CD334
Target Type Clinical trial Target
Gene Name FGFR4
Biochemical Class Kinase
UniProt ID
FGFR4_HUMAN
Ligand General Information  Top
Ligand Name N-(4-{[3-(3,5-Dimethoxyphenyl)-7-{[4-(4-Methylpiperazin-1-Yl)phenyl]amino}-2-Oxo-3,4-Dihydropyrimido[4,5-D]pyrimidin-1(2h)-Yl]methyl}phenyl)propanamide Ligand Info
Canonical SMILES CCC(=O)NC1=CC=C(C=C1)CN2C3=NC(=NC=C3CN(C2=O)C4=CC(=CC(=C4)OC)OC)NC5=CC=C(C=C5)N6CCN(CC6)C
InChI 1S/C35H40N8O4/c1-5-32(44)37-26-8-6-24(7-9-26)22-43-33-25(23-42(35(43)45)29-18-30(46-3)20-31(19-29)47-4)21-36-34(39-33)38-27-10-12-28(13-11-27)41-16-14-40(2)15-17-41/h6-13,18-21H,5,14-17,22-23H2,1-4H3,(H,37,44)(H,36,38,39)
InChIKey DKHGWJNITASDGF-UHFFFAOYSA-N
PubChem Compound ID 121426117
Drug Binding Sites of Target  Top
PDB ID: 4QQ5      Crystal Structure of FGF Receptor (FGFR) 4 Kinase Harboring the V550L Gate-Keeper Mutation in Complex With FIIN-2, an Irreversible Tyrosine Kinase Inhibitor Capable of Overcoming FGFR Kinase Gate-Keeper Mutations
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [1]
PDB Sequence
QDPLLAGLVS
456
LDLPLDPLWE
466
FPRDRLVLGK
476
PLGEGCFGQV
486
VRAEAFGMDQ
501

ASTVAVKMLK
511
DNASDKDLAD
521
LVSEMEVMKL
531
IGRHKNIINL
541
LGVCTQEGPL
551

YVILECAAKG
561
NLREFLRARR
571
PPGPLSFPVL
594
VSCAYQVARG
604
MQYLESRKCI
614

HRDLAARNVL
624
VTEDNVMKIA
634
DFGLALPVKW
660
MAPEALFDEV
670
YTHQSDVWSF
680

GILLWEIFTL
690
GGSPYPGIPV
700
EELFSLLREG
710
HRMDRPPHCP
720
PELYGLMREC
730

WHAAPSQRPT
740
FKQLVEALDK
750
VLLAV
Residue
Distance (Å)
LEU478
3.428
GLY479
3.941
GLU480
2.974
GLY481
3.288
CYS482
1.747
PHE483
3.455
VAL486
3.703
ALA506
4.059
LYS508
3.439
GLU525
3.531
MET529
3.895
ILE539
3.709
LEU555
3.376
Residue
Distance (Å)
GLU556
3.163
CYS557
3.715
ALA558
2.635
ALA559
3.560
LYS560
4.474
GLY561
3.531
GLU565
3.868
LEU624
3.502
ILE633
4.679
ALA634
3.482
ASP635
3.028
PHE636
3.073
LEU638
3.756
PDB ID: 4QQC      Crystal Structure of FGF Receptor (FGFR) 4 Kinase Domain in Complex with FIIN-2, an Irreversible Tyrosine Kinase Inhibitor Capable of Overcoming FGFR Kinase Gate-Keeper Mutations
Method X-ray diffraction Resolution 2.40 Å Mutation Yes [2]
PDB Sequence
DPLLAGLVSL
452
DLPLDPLWEF
462
PRDRLVLGKP
472
LGEGCFGQVV
482
RAEAFGMDQA
497

STVAVKMLKD
507
NASDKDLADL
517
VSEMEVMKLI
527
GRHKNIINLL
537
GVCTQEGPLY
547

VIVECAAKGN
557
LREFLRARRP
567
PGPLSFPVLV
590
SCAYQVARGM
600
QYLESRKCIH
610

RDLAARNVLV
620
TEDNVMKIAD
630
FGLLPVKWMA
657
PEALFDEVYT
667
HQSDVWSFGI
677

LLWEIFTLGG
687
SPYPGIPVEE
697
LFSLLREGHR
707
MDRPPHCPPE
717
LYGLMRECWH
727

AAPSQRPTFK
737
QLVEALDKVL
747
LAV
Residue
Distance (Å)
LEU473
3.735
GLY474
4.068
GLU475
2.408
GLY476
3.850
CYS477
1.642
PHE478
3.513
VAL481
3.612
ALA501
4.263
LYS503
3.430
GLU520
3.626
MET524
3.635
ILE534
3.857
VAL548
3.694
VAL550
3.704
Residue
Distance (Å)
GLU551
3.196
CYS552
3.668
ALA553
2.700
ALA554
3.768
LYS555
4.685
GLY556
3.762
GLU560
3.791
LEU619
3.439
ILE628
4.889
ALA629
3.636
ASP630
3.224
PHE631
3.658
GLY632
4.517
References  Top
REF 1 DFG-out mode of inhibition by an irreversible type-1 inhibitor capable of overcoming gate-keeper mutations in FGF receptors. ACS Chem Biol. 2015 Jan 16;10(1):299-309.
REF 2 Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):E4869-77.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.