Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T08391 Target Info
Target Name Janus kinase 2 (JAK-2)
Synonyms Tyrosine-protein kinase JAK2
Target Type Successful Target
Gene Name JAK2
Biochemical Class Kinase
UniProt ID
JAK2_HUMAN
Ligand General Information  Top
Ligand Name GLPG-0634 Ligand Info
Canonical SMILES C1CC1C(=O)NC2=NN3C(=N2)C=CC=C3C4=CC=C(C=C4)CN5CCS(=O)(=O)CC5
InChI 1S/C21H23N5O3S/c27-20(17-8-9-17)23-21-22-19-3-1-2-18(26(19)24-21)16-6-4-15(5-7-16)14-25-10-12-30(28,29)13-11-25/h1-7,17H,8-14H2,(H,23,24,27)
InChIKey RIJLVEAXPNLDTC-UHFFFAOYSA-N
PubChem Compound ID 49831257
Drug Binding Sites of Target  Top
PDB ID: 4P7E      Triazolopyridine compounds as selective JAK1 inhibitors: from hit identification to GLPG0634
Method X-ray diffraction Resolution 2.40 Å Mutation Yes [1]
PDB Sequence
QFEERHLKFL
852
QQLGKGNFGS
862
VEMCRYDPLQ
872
DNTGEVVAVK
882
KLQHSTEEHL
892

RDFEREIEIL
902
KSLQHDNIVK
912
YKGVCYSNLK
926
LIMEYLPYGS
936
LRDYLQKHKE
946

RIDHIKLLQY
956
TSQICKGMEY
966
LGTKRYIHRD
976
LATRNILVEN
986
ENRVKIGDFG
996

LTKVLPQDKE
1006
KVKEPGESPI
1018
FWYAPESLTE
1028
SKFSVASDVW
1038
SFGVVLYELF
1048

TYIEKSKSPP
1058
AEFMRMIGNG
1071
QMIVFHLIEL
1081
LKNNGRLPRP
1091
DGCPDEIYMI
1101

MTECWNNNVN
1111
QRPSFRDLAL
1121
RVDQIRDQMA
1131
G
Residue
Distance (Å)
LEU855
3.687
GLY856
3.402
LYS857
3.932
GLY858
3.890
GLY861
3.287
SER862
3.141
VAL863
3.441
ALA880
3.373
LYS882
3.512
VAL911
3.824
MET929
3.739
GLU930
3.078
Residue
Distance (Å)
TYR931
3.361
LEU932
2.772
PRO933
3.972
TYR934
4.057
GLY935
3.182
SER936
4.628
ARG980
4.203
ASN981
3.947
LEU983
3.633
GLY993
3.558
ASP994
3.319
PDB ID: 5UT5      JAK2 JH2 in complex with GLPG0634
Method X-ray diffraction Resolution 1.90 Å Mutation Yes [2]
PDB Sequence
FHKIRNEDLI
546
FNESLGQGTF
556
TKIFKGVRRE
566
VGDYGQLHET
576
EVLLKVLDKA
586

HRNYSESFFE
596
AASMMSKLSH
606
KHLVLNYGVC
616
VCGDENILVQ
626
EFVKFGSLDT
636

YLKKNKNCIN
646
ILWKLEVAKQ
656
LAAAMHFLEE
666
NTLIHGNVCA
676
KNILLIREED
686

RKTGNPPFIK
696
LSDPGISITV
706
LPKDILQERI
716
PWVPPECIEN
726
PKNLNLATDK
736

WSFGTTLWEI
746
CSGGDKPLSA
756
LDSQRKLQFY
766
EDRHQLPAPK
776
AAELANLINN
786

CMDYEPDHRP
796
SFRAIIRDLN
806
SL
Residue
Distance (Å)
LEU551
3.713
GLY552
4.322
GLN553
3.769
ILE559
3.702
LEU579
3.515
VAL610
4.275
GLN626
3.858
GLU627
3.257
PHE628
3.468
VAL629
2.654
Residue
Distance (Å)
LYS630
3.389
PHE631
3.824
GLY632
3.432
SER633
3.372
ASP635
4.179
THR636
3.622
LYS677
3.753
ASN678
4.432
LEU680
3.315
SER698
4.111
References  Top
REF 1 Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634. J Med Chem. 2014 Nov 26;57(22):9323-42.
REF 2 JAK2 JH2 Fluorescence Polarization Assay and Crystal Structures for Complexes with Three Small Molecules. ACS Med Chem Lett. 2017 May 17;8(6):614-617.

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