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 Benzamide, N-cyclopropyl-4-[6-(2,3-difluoro-4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-methyl- Ligand Info
Canonical SMILES CC1=C(C=CC(=C1)C2=CN=C3N2N=C(C=C3NCCC(F)(F)F)OC4=C(C(=C(C=C4)OC)F)F)C(=O)NC5CC5
InChI 1S/C27H24F5N5O3/c1-14-11-15(3-6-17(14)26(38)35-16-4-5-16)19-13-34-25-18(33-10-9-27(30,31)32)12-22(36-37(19)25)40-21-8-7-20(39-2)23(28)24(21)29/h3,6-8,11-13,16,33H,4-5,9-10H2,1-2H3,(H,35,38)
InChIKey WNEILUNVMHVMPH-UHFFFAOYSA-N
PubChem Compound ID 78320750
Drug Binding Sites of Target  Top
PDB ID: 5NAD      TTK kinase domain in complex with BAY 1217389
Method X-ray diffraction Resolution 2.80 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

GIANQMQPDV
687
NYMPPEAIKD
697
MKISPKSDVW
718
SLGCILYYMT
728
YGKTPFQQII
738

NQISKLHAII
748
DPNHEIEFPD
758
IPEKDLQDVL
768
KCCLKRDPKQ
778
RISIPELLAH
788

PYVQIQ
Residue
Distance (Å)
LYS529
3.925
ILE531
3.426
GLY532
3.757
VAL539
4.387
GLN541
2.860
ALA551
3.841
LYS553
3.125
GLU571
3.339
LEU575
3.716
ILE586
3.121
MET600
4.138
MET602
3.281
GLU603
3.430
CYS604
3.657
GLY605
2.794
Residue
Distance (Å)
ASN606
3.123
ILE607
4.495
ASP608
3.683
ALA651
2.956
ASN652
3.911
PHE653
4.837
LEU654
3.517
ILE663
2.926
ASP664
3.849
PHE665
4.338
GLN670
4.095
MET671
2.748
GLN672
3.822
PRO673
3.609
PDB ID: 6TND      X-RAY STRUCTURE OF MPS1 IN COMPLEX WITH COMPOUND 79
Method X-ray diffraction Resolution 2.58 Å Mutation No [2]
PDB Sequence
ECISVKGRIY
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

GIANQMQPTV
687
NYMPPEAIKD
697
MISPKSDVWS
719
LGCILYYMTY
729
GKTPFQQIIN
739

QISKLHAIID
749
PNHEIEFPDI
759
PEKDLQDVLK
769
CCLKRDPKQR
779
ISIPELLAHP
789

YVQI
Residue
Distance (Å)
LYS529
2.895
ILE531
3.264
GLY532
3.476
SER533
4.363
VAL539
3.918
GLN541
3.065
ALA551
3.470
LYS553
2.625
GLU571
3.357
LEU575
3.501
ILE586
4.055
MET600
3.642
MET602
3.312
GLU603
3.446
CYS604
3.317
Residue
Distance (Å)
GLY605
2.734
ASN606
3.572
ILE607
4.179
ASP608
4.010
LYS649
4.869
ALA651
3.162
ASN652
4.191
LEU654
3.435
ILE663
2.530
ASP664
3.722
PHE665
4.514
MET671
3.232
GLN672
3.542
PRO673
3.703
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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