Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 6-{[3-(Cyanomethoxy)-4-(1-Methyl-1h-Pyrazol-4-Yl)phenyl]amino}-2-(Cyclohexylamino)pyridine-3-Carbonitrile | Ligand Info | |||
| Canonical SMILES | CN1C=C(C=N1)C2=C(C=C(C=C2)NC3=NC(=C(C=C3)C#N)NC4CCCCC4)OCC#N | ||||
| InChI | 1S/C24H25N7O/c1-31-16-18(15-27-31)21-9-8-20(13-22(21)32-12-11-25)28-23-10-7-17(14-26)24(30-23)29-19-5-3-2-4-6-19/h7-10,13,15-16,19H,2-6,12H2,1H3,(H2,28,29,30) | ||||
| InChIKey | OVHGMKGIRAADEL-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 70799413 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3WYX CRYSTAL STRUCTURE OF HUMAN MPS1 CATALYTIC DOMAIN IN COMPLEX WITH 6-((3-(cyanomethoxy)-4-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-2-(cyclohexylamino)nicotinonitrile | ||||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [1] |
| PDB Sequence |
ECISVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPGT 686 VNYMPPEAIK696 DMSISPKSDV717 WSLGCILYYM727 TYGKTPFQQI737 INQISKLHAI 747 IDPNHEIEFP757 DIPEKDLQDV767 LKCCLKRDPK777 QRISIPELLA787 HPYVQIQT |
|||||
|
|
LYS529
4.583
ILE531
3.242
GLY532
3.793
VAL539
3.753
GLN541
3.529
ILE549
4.204
ALA551
3.407
LYS553
3.981
ILE586
3.715
MET602
3.562
GLU603
3.208
CYS604
2.651
|
|||||
| PDB ID: 5AP1 Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [2] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 VVKDVGVNYM690 PPEAIKDMSS700 KSKISPKSDV717 WSLGCILYYM727 TYGKTPFQQI 737 INQISKLHAI747 IDPNHEIEFP757 DIPEKDLQDV767 LKCCLKRDPK777 QRISIPELLA 787 HPYVQIQT
|
|||||
|
|
ILE531
3.507
GLY532
4.112
VAL539
3.741
GLN541
2.893
ALA551
3.507
LYS553
3.894
ILE586
3.711
MET602
3.659
GLU603
3.737
CYS604
2.742
GLY605
3.649
|
|||||
| PDB ID: 5AP4 Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. | ||||||
| Method | X-ray diffraction | Resolution | 2.85 Å | Mutation | Yes | [2] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNGWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANMQPDQ 683 VGVNYMPPEA694 IKDISPKSDV717 WSLGCILYYM727 TYGKTPFQQI737 INQISKLHAI 747 IDPNHEIEFP757 DIPEKDLQDV767 LKCCLKRDPK777 QRISIPELLA787 HPYVQIQ |
|||||
|
|
ILE531
3.434
GLY532
3.986
VAL539
3.857
GLN541
2.934
ALA551
3.665
LYS553
4.244
ILE586
3.514
MET602
3.785
GLU603
3.721
CYS604
2.697
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A unique hinge binder of extremely selective aminopyridine-based Mps1 (TTK) kinase inhibitors with cellular activity. Bioorg Med Chem. 2015 May 1;23(9):2247-60. | ||||
| REF 2 | Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. Cancer Res. 2015 Aug 15;75(16):3340-54. | ||||
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