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 T74977 Target Info
Target Name Dual specificity protein kinase TTK (MPS1)
Synonyms Tyrosine threonine kinase; Phosphotyrosine picked threonine-protein kinase; PYT; MPS1L1
Target Type Clinical trial Target
Gene Name TTK
Biochemical Class Kinase
UniProt ID
TTK_HUMAN
Ligand General Information  Top
Ligand Name BAY1161909 Ligand Info
Canonical SMILES CC(C1=CC=C(C=C1)F)C(=O)NC2=CC=C(C=C2)C3=CN4C(=NC(=N4)NC5=C(C=C(C=C5)S(=O)(=O)C)OC)C=C3
InChI 1S/C29H26FN5O4S/c1-18(19-4-9-22(30)10-5-19)28(36)31-23-11-6-20(7-12-23)21-8-15-27-33-29(34-35(27)17-21)32-25-14-13-24(40(3,37)38)16-26(25)39-2/h4-18H,1-3H3,(H,31,36)(H,32,34)/t18-/m1/s1
InChIKey NRJKIOCCERLIDG-GOSISDBHSA-N
PubChem Compound ID 71599640
Drug Binding Sites of Target  Top
PDB ID: 5N9S      TTK kinase domain in complex with BAY 1161909
Method X-ray diffraction Resolution 2.30 Å Mutation No [1]
PDB Sequence
QSMSVKGRIY
525
SILKQIGSGG
535
SSKVFQVLNE
545
KKQIYAIKYV
555
NLEEADNQTL
565

DSYRNEIAYL
575
NKLQQHSDKI
585
IRLYDYEITD
595
QYIYMVMECG
605
NIDLNSWLKK
615

KKSIDPWERK
625
SYWKNMLEAV
635
HTIHQHGIVH
645
SDLKPANFLI
655
VDGMLKLIDF
665

GIANQMQPDS
682
QVGVNYMPPE
693
AIKDKISPKS
715
DVWSLGCILY
725
YMTYGKTPFQ
735

QIINQISKLH
745
AIIDPNHEIE
755
FPDIPEKDLQ
765
DVLKCCLKRD
775
PKQRISIPEL
785

LAHPYVQIQ
Residue
Distance (Å)
LYS529
4.067
ILE531
3.673
VAL539
4.194
GLN541
3.490
ALA551
3.501
LYS553
3.088
VAL555
3.818
TYR568
3.404
GLU571
3.624
ILE572
3.761
ILE586
4.107
ILE598
3.600
MET600
3.031
MET602
3.124
Residue
Distance (Å)
GLU603
3.253
CYS604
3.795
GLY605
2.989
ASN606
3.244
ILE607
4.073
ASP608
3.483
SER611
3.496
LEU654
3.475
ILE663
3.354
ASP664
4.024
ALA668
3.672
GLN670
4.263
ASP681
3.507
PDB ID: 6TNB      X-RAY STRUCTURE OF MPS1 IN COMPLEX WITH COMPOUND 41
Method X-ray diffraction Resolution 2.65 Å Mutation No [2]
PDB Sequence
CISVKGRIYS
526
ILKQIGSGGS
536
SKVFQVLNEK
546
KQIYAIKYVN
556
LEEADNQTLD
566

SYRNEIAYLN
576
KLQQHSDKII
586
RLYDYEITDQ
596
YIYMVMECGN
606
IDLNSWLKKK
616

KSIDPWERKS
626
YWKNMLEAVH
636
TIHQHGIVHS
646
DLKPANFLIV
656
DGMLKLIDFG
666

IANGVNYMPP
692
EAIKDMKISP
713
KSDVWSLGCI
723
LYYMTYGKTP
733
FQQIINQISK
743

LHAIIDPNHE
753
IEFPDIPEKD
763
LQDVLKCCLK
773
RDPKQRISIP
783
ELLAHPYVQI
793

Q
Residue
Distance (Å)
LYS529
4.014
ILE531
3.288
VAL539
4.100
GLN541
4.216
ALA551
3.430
LYS553
2.660
VAL555
3.929
TYR568
3.322
GLU571
3.968
ILE572
3.506
ILE586
3.981
ILE598
3.420
MET600
3.428
Residue
Distance (Å)
MET602
3.000
GLU603
3.236
CYS604
3.691
GLY605
2.767
ASN606
3.454
ILE607
3.971
ASP608
3.951
SER611
3.244
LEU654
3.534
ILE663
3.126
ASP664
4.062
ALA668
3.543
References  Top
REF 1 Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity. J Mol Biol. 2017 Jul 7;429(14):2211-2230.
REF 2 Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase. J Med Chem. 2020 Aug 13;63(15):8025-8042.

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