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 | Tert-Butyl 6-((2-Chloro-4-(Dimethylcarbamoyl)phenyl)amino)-2-(1-Methyl-1h-Pyrazol-4-Yl)-1h-Pyrrolo[3,2-C]pyridine-1-Carboxylate | Ligand Info | |||
| Canonical SMILES | CC(C)(C)OC(=O)N1C(=CC2=CN=C(C=C21)NC3=C(C=C(C=C3)C(=O)N(C)C)Cl)C4=CN(N=C4)C | ||||
| InChI | 1S/C25H27ClN6O3/c1-25(2,3)35-24(34)32-20(17-13-28-31(6)14-17)10-16-12-27-22(11-21(16)32)29-19-8-7-15(9-18(19)26)23(33)30(4)5/h7-14H,1-6H3,(H,27,29) | ||||
| InChIKey | KYBALIQJYSWGLI-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 68310278 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4C4G Structure-based design of orally bioavailable pyrrolopyridine inhibitors of the mitotic kinase MPS1 | ||||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [1] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIAVGVNYM 690 PPEAIKDISP713 KSDVWSLGCI723 LYYMTYGKTP733 FQQIINQISK743 LHAIIDPNHE 753 IEFPDIPEKD763 LQDVLKCCLK773 RDPKQRISIP783 ELLAHPYVQI793 Q |
|||||
|
|
LYS529
4.253
ILE531
3.222
GLY532
3.979
VAL539
3.900
GLN541
3.897
ALA551
3.395
LYS553
2.958
LEU575
3.858
ILE586
3.247
MET600
3.927
MET602
3.317
|
|||||
| PDB ID: 4C4H Structure-based design of orally bioavailable pyrrolopyridine inhibitors of the mitotic kinase MPS1 | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [1] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGS536 SKVFQVLNEK546 KQIYAIKYVN556 LEEADNQTLD566 SYRNEIAYLN 576 KLQQHSDKII586 RLYDYEITDQ596 YIYMVMECGN606 IDLNSWLKKK616 KSIDPWERKS 626 YWKNMLEAVH636 TIHQHGIVHS646 DLKPANFLIV656 DGMLKLIDFG666 IATVNYMPPE 693 AIKDISPKSD716 VWSLGCILYY726 MTYGKTPFQQ736 IINQISKLHA746 IIDPNHEIEF 756 PDIPEKDLQD766 VLKCCLKRDP776 KQRISIPELL786 AHPYVQIQ
|
|||||
|
|
ILE531
3.406
GLY532
3.760
VAL539
3.677
GLN541
3.585
ALA551
3.240
LYS553
3.250
GLU571
4.646
LEU575
4.243
ILE586
4.247
MET600
4.649
MET602
3.518
|
|||||
| PDB ID: 5AP5 Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNGWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIAGTVNYM 690 PPEAIKDMIS712 PKSDVWSLGC722 ILYYMTYGKT732 PFQQIINQIS742 KLHAIIDPNH 752 EIEFPDIPEK762 DLQDVLKCCL772 KRDPKQRISI782 PELLAHPYVQ792 IQ |
|||||
|
|
ILE531
3.519
GLY532
4.166
VAL539
3.764
GLN541
3.894
ALA551
3.302
LYS553
3.149
GLU571
4.678
LEU575
4.132
ILE586
3.413
MET600
4.034
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1). J Med Chem. 2013 Dec 27;56(24):10045-65. | ||||
| 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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