TTK

Summary

TTK (TTK protein kinase, HGNC:12401) is a protein-coding gene on chromosome 6q14.1, encoding Dual specificity protein kinase TTK (P33981). Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments. It is a selective cancer dependency (DepMap: 89.9% of cell lines).

This gene encodes a dual specificity protein kinase with the ability to phosphorylate tyrosine, serine and threonine. Associated with cell proliferation, this protein is essential for chromosome alignment at the centromere during mitosis and is required for centrosome duplication. It has been found to be a critical mitotic checkpoint protein for accurate segregation of chromosomes during mitosis. Tumorigenesis may occur when this protein fails to degrade and produces excess centrosomes resulting in aberrant mitotic spindles. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7272 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 135 total — 1 pathogenic
• Druggable target: yes — 36 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 89.9% of screened cell lines
• MANE Select transcript: NM_003318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12401
Approved symbol	TTK
Name	TTK protein kinase
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	PYT, MPS1, MPS1L1, CT96, MPH1
Ensembl gene	ENSG00000112742
Ensembl biotype	protein_coding
OMIM	604092
Entrez	7272

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000230510, ENST00000369798, ENST00000430061, ENST00000502580, ENST00000504040, ENST00000504590, ENST00000509313, ENST00000509894, ENST00000511260, ENST00000515751, ENST00000627129, ENST00000867612, ENST00000936244, ENST00000936245, ENST00000936246, ENST00000936247, ENST00000936248, ENST00000936249

RefSeq mRNA: 2 — MANE Select: NM_003318 NM_001166691, NM_003318

CCDS: CCDS4993, CCDS55040

Canonical transcript exons

ENST00000369798 — 22 exons

Exon	Start	End
ENSE00000759354	80011729	80011801
ENSE00000759356	80011886	80011980
ENSE00000759358	80013279	80013366
ENSE00000759363	80027885	80028011
ENSE00000759364	80031467	80031559
ENSE00000759365	80034985	80035142
ENSE00000759366	80035266	80035417
ENSE00000759368	80037967	80038047
ENSE00000759370	80040196	80040280
ENSE00000759371	80040606	80040703
ENSE00000798027	80005842	80005982
ENSE00000798028	80036475	80036599
ENSE00001450959	80004649	80004713
ENSE00002035648	80042119	80042527
ENSE00002036427	80011434	80011548
ENSE00003498599	80022324	80022472
ENSE00003530004	80008386	80008492
ENSE00003579064	80026378	80026514
ENSE00003579671	80014463	80014586
ENSE00003601890	80039696	80039872
ENSE00003604712	80010814	80010957
ENSE00003688914	80007809	80008031

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 97.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4047 / max 422.9215, expressed in 1127 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68701	8.2074	1116
68700	0.1973	77

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.85	gold quality
ventricular zone	UBERON:0003053	95.55	gold quality
oocyte	CL:0000023	93.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.45	gold quality
ganglionic eminence	UBERON:0004023	90.27	gold quality
sperm	CL:0000019	89.89	gold quality
embryo	UBERON:0000922	89.16	gold quality
male germ cell	CL:0000015	87.95	gold quality
trabecular bone tissue	UBERON:0002483	86.65	gold quality
testis	UBERON:0000473	85.19	gold quality
right testis	UBERON:0004534	85.04	gold quality
left testis	UBERON:0004533	84.87	gold quality
bone marrow	UBERON:0002371	83.59	gold quality
thymus	UBERON:0002370	80.52	gold quality
rectum	UBERON:0001052	77.91	gold quality
stromal cell of endometrium	CL:0002255	77.88	gold quality
bone marrow cell	CL:0002092	76.38	gold quality
adrenal tissue	UBERON:0018303	76.02	gold quality
esophagus mucosa	UBERON:0002469	75.22	gold quality
lower esophagus mucosa	UBERON:0035834	75.05	gold quality
vermiform appendix	UBERON:0001154	74.19	gold quality
mucosa of transverse colon	UBERON:0004991	73.65	gold quality
esophagus squamous epithelium	UBERON:0006920	73.37	silver quality
endometrium epithelium	UBERON:0004811	72.93	gold quality
oral cavity	UBERON:0000167	72.91	gold quality
adult organism	UBERON:0007023	72.32	gold quality
gingival epithelium	UBERON:0001949	72.26	silver quality
caecum	UBERON:0001153	70.56	gold quality
colonic epithelium	UBERON:0000397	70.50	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDR2, E2F4, TP53

miRNA regulators (miRDB)

24 targeting TTK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-376A-2-5P	96.43	68.06	715
HSA-MIR-759	96.16	66.77	873

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• human Mps1(TTK kinase) is essential for the establishment and/or maintenance of the spindle assembly checkpoint, but dispensable for centrosome duplication. (PMID:11927556)
• is required by cells to arrest in mitosis in response to spindle defects and kinetochore defects resulting from the loss of the kinesin-like protein (PMID:12686615)
• is required for centrosome duplication and for the normal progression of mitosis (PMID:14657364)
• The inter-relationship between TTK and TACC2 established provides new avenue to study centrosome and spindle dynamics underlying cell divisional control. (PMID:15304323)
• TTK functions upstream from CHK2 in response to DNA damage (PMID:15618221)
• findings indicate that Aurora-A and hMPS1 aberrations are uncommon in aggressive lymphomas but Aurora-A overexpression may contribute to numerical chromosomal alterations in occasional mantle cell lymphomas (PMID:16080195)
• MPS1 is negatively regulated by the p53 protein after DNA damage by SN-38. The lack of suppression of MPS1 in p53-deficient cells leads to damage-induced apoptosis. (PMID:16446370)
• Results suggest that MPS1-dependent BLM phosphorylation is important for ensuring accurate chromosome segregation, and its deregulation may contribute to cancer. (PMID:16864798)
• analysis of a novel functional link between Mps1 and Smads in a non-canonical Smad signaling pathway (PMID:17452325)
• Mortalin binds to Mps1, and is phosphorylated by Mps1 on Thr62 and Ser65 (PMID:17573779)
• site-specific Mps1 autophosphorylation within the activation loop is required for full activity in vitro and function in vivo. (PMID:17728254)
• Data show that TTK protein kinase, lymphocyte antigen 6 complex locus K and insulin-like growth factor (IGF)-II mRNA binding protein 3 are tumor-associated antigens recognized by cytotoxic T lymphocytes and HLA-A24-restricted epitope peptides. (PMID:17784873)
• Mps1 mediates cyclin A-dependent centrosome reduplication (PMID:17804818)
• PRP4 is a spindle assembly checkpoint protein required for MPS1 localization to the kinetochores. (PMID:17998396)
• B-Raf(V600E) signaling deregulates the mitotic spindle checkpoint through stabilizing Mps1 levels in melanoma cells. (PMID:18071315)
• the endogenous Mps1 in mitotic HeLa cells is phosphorylated on T676, a residue in the activation loop. (PMID:18083840)
• MPS1 phosphorylates borealin to control aurora kinase activity and chromosome alignment. (PMID:18243099)
• crystallographic analysis of the catalytic domain of the mitotic checkpoint kinase Mps1 in complex with SP600125 (PMID:18480048)
• In human cells, Mps1 catalytic activity is required for spindle checkpoint function and recruitment of Mad2. (PMID:18541701)
• Results reveal the complexity of Mps1 regulation by multi-site phosphorylation, and demonstrate conclusively that phosphorylated Mps1 associates with centrosomes in mitotic human cells. (PMID:18680479)
• TTK controls nuclear targeting of c-Abl by 14-3-3-coupled phosphorylation in response to oxidative stress. (PMID:18794806)
• Results demonstrate that phosphorylation of Mps1 at T12 and S15 is required for Mps1 recruitment to the kinetochore. (PMID:18923149)
• Mps1 is a major but not the exclusive kinase that specifies BubR1 phosphorylation in vivo. (PMID:19015317)
• identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase (PMID:19120698)
• a regulatory loop between TTK/hMps1 and CHK2 whereby DNA damage-activated CHK2 may facilitate the stabilization of TTK/hMps1, therefore maintaining the checkpoint control. (PMID:19151762)
• Stabilization and activation of p53 by spindle disruption requires the spindle checkpoint kinase TTK/hMps1. (PMID:19332559)
• Microtubule inhibitor-induced phosphorylation of BNIP3, Bcl-2 and Bcl-xL occurs independently of the AKT/mTor and JNK kinase pathways and requires Mps1 mitotic checkpoint kinase activity (PMID:20100468)
• Mps1 has multiple controls over mitotic checkpoint activity; short-term inhibition of Mps1 catalytic activity is sufficient to kill cells (PMID:20422024)
• Mps1 kinase activity ensures accurate chromosome segregation through its recruitment to kinetochores of mitotic checkpoint proteins (PMID:20624898)
• Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex. (PMID:20624899)
• Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine. (PMID:20624901)
• Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling. (PMID:20624902)
• the sequential actions of the APC-c(Cdc20) and APC-c(Cdh1) ubiquitin ligases regulate the clearance of Mps1 levels and are critical for Mps1 functions during the cell cycle in human cells. (PMID:20729194)
• Data show that OAZ promotes the removal of Mps1 from centrosomes, and centrosome overproduction caused by reducing OAZ activity requires Mps1. (PMID:20861309)
• Mps1 mutant without the unstructured tail region is defective in mediating spindle assembly checkpoint activation. (PMID:20884615)
• Release of Mps1 from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition. (PMID:20937696)
• Mps1-dependent phosphorylation of Cetn2 stimulates the canonical centriole assembly pathway. (PMID:20980622)
• High frequency of TTK mutations is associated with microsatellite-unstable colorectal cancer. (PMID:21163887)
• Data suggest that high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy. (PMID:21402910)
• conditional inactivation of Mps1 inactivates the mitotic checkpoint, increases chromosome alignment defects, and compromises cell viability in vitro (PMID:21475725)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttk	ENSDARG00000041361
mus_musculus	Ttk	ENSMUSG00000038379
rattus_norvegicus	Ttk	ENSRNOG00000029055

Paralogs (2): TLK2 (ENSG00000146872), TLK1 (ENSG00000198586)

Protein

Protein identifiers

Dual specificity protein kinase TTK — P33981 (reviewed: P33981)

Alternative names: Phosphotyrosine picked threonine-protein kinase

All UniProt accessions (5): D6REX1, D6RF82, D6RFY1, D6RIC6, P33981

UniProt curated annotations — full annotation on UniProt →

Function. Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments. Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint. Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore. Phosphorylates SKA3 at ‘Ser-34’ leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments. Phosphorylates KNL1, KNTC1 and autophosphorylates. Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment.

Subunit / interactions. Interacts with TPR; the interactions occurs in a microtubule-independent manner. Interacts with MAD1L1 and MAD2L1.

Tissue specificity. Present in rapidly proliferating cell lines.

Activity regulation. Inhibited by the ATP-competitive kinase inhibitor, SP600125.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P33981-1	1	yes
P33981-2	2

RefSeq proteins (2): NP_001160163, NP_003309* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR027084	Mps1_cat	Domain

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.12.1 — dual-specificity kinase (BRENDA: 51 organisms, 125 substrates, 188 inhibitors, 14 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.019–0.1185	7
HISTONE H1	0.006–0.012	5

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (68 total): helix 21, modified residue 14, strand 13, turn 4, region of interest 2, sequence variant 2, mutagenesis site 2, sequence conflict 2, compositionally biased region 2, binding site 2, chain 1, domain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

78 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4H7Y	X-RAY DIFFRACTION	1.8
4JS8	X-RAY DIFFRACTION	1.94
7LQD	X-RAY DIFFRACTION	1.95
5EI6	X-RAY DIFFRACTION	2.01
5AP1	X-RAY DIFFRACTION	2.05
5AP6	X-RAY DIFFRACTION	2.1
5N93	X-RAY DIFFRACTION	2.1
5AP0	X-RAY DIFFRACTION	2.15
5EI8	X-RAY DIFFRACTION	2.17
5EH0	X-RAY DIFFRACTION	2.18
5EHO	X-RAY DIFFRACTION	2.18
4B94	X-RAY DIFFRACTION	2.2
4JT3	X-RAY DIFFRACTION	2.2
5MRB	X-RAY DIFFRACTION	2.2
5EHY	X-RAY DIFFRACTION	2.26
5N87	X-RAY DIFFRACTION	2.29
3CEK	X-RAY DIFFRACTION	2.3
3HMP	X-RAY DIFFRACTION	2.3
3WZK	X-RAY DIFFRACTION	2.3
5N84	X-RAY DIFFRACTION	2.3
5N9S	X-RAY DIFFRACTION	2.3
6TNC	X-RAY DIFFRACTION	2.3
7CIL	X-RAY DIFFRACTION	2.3
4ZEG	X-RAY DIFFRACTION	2.33
4C4F	X-RAY DIFFRACTION	2.36
4O6L	X-RAY DIFFRACTION	2.38
3HMO	X-RAY DIFFRACTION	2.4
3VQU	X-RAY DIFFRACTION	2.4
7CHN	X-RAY DIFFRACTION	2.4
7CHT	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33981-F1	64.11	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 647 (proton acceptor)

Ligand- & substrate-binding residues (2): 531–539; 553

Post-translational modifications (14): 7, 33, 37, 80, 281, 317, 321, 360, 363, 393, 436, 455, 821, 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
664	loss of kinase activity.
686	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 403 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, HORIUCHI_WTAP_TARGETS_DN, GNF2_CENPF, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_NUCLEAR_DIVISION, PAL_PRMT5_TARGETS_UP, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_CHROMOSOME_LOCALIZATION

GO Biological Process (15): spindle organization (GO:0007051), mitotic spindle organization (GO:0007052), chromosome segregation (GO:0007059), mitotic spindle assembly checkpoint signaling (GO:0007094), positive regulation of cell population proliferation (GO:0008284), female meiosis chromosome segregation (GO:0016321), meiotic spindle assembly checkpoint signaling (GO:0033316), protein localization to kinetochore (GO:0034501), positive regulation of SMAD protein signal transduction (GO:0060391), repair of mitotic kinetochore microtubule attachment defect (GO:0140273), protein localization to meiotic spindle midzone (GO:1903096), nuclear division (GO:0000280), protein phosphorylation (GO:0006468), protein localization to chromosome (GO:0034502), nuclear chromosome segregation (GO:0098813)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), identical protein binding (GO:0042802), kinetochore binding (GO:0043515), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): kinetochore (GO:0000776), nucleus (GO:0005634), cytoplasm (GO:0005737), spindle (GO:0005819), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
cell cycle process	2
mitotic cell cycle	2
spindle assembly checkpoint signaling	2
binding	2
intracellular membraneless organelle	2
cellular anatomical structure	2
microtubule cytoskeleton organization	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
negative regulation of mitotic metaphase/anaphase transition	1
mitotic spindle checkpoint signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
female meiotic nuclear division	1
meiotic chromosome segregation	1
meiotic spindle checkpoint signaling	1
meiotic cell cycle	1
protein localization to chromosome, centromeric region	1
protein localization to condensed chromosome	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of intracellular signal transduction	1
mitotic metaphase chromosome alignment	1
repair of kinetochore microtubule attachment defect	1
mitotic cell cycle process	1
protein localization to meiotic spindle	1
organelle fission	1
phosphorylation	1
protein modification process	1
protein localization to organelle	1
chromosome segregation	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1

Protein interactions and networks

STRING

2662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTK	BMI1	P35226	964
TTK	R4GMX3	R4GMX3	963
TTK	BUB1	O43683	946
TTK	RING1	Q06587	920
TTK	BUB1B	O60566	919
TTK	MAD2L1	Q13257	911
TTK	PCGF2	P35227	902
TTK	BUB3	O43684	898
TTK	CDC20	Q12834	869
TTK	FANCM	Q8IYD8	783
TTK	CENPE	Q02224	776
TTK	CARMIL2	Q6F5E8	763
TTK	CCNB2	O95067	736
TTK	CENPF	P49454	723
TTK	TOP2A	P11388	720

IntAct

116 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
LPAR4	POTEF	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SV2A	EXTL3	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
TACC2	TTK	psi-mi:“MI:0915”(physical association)	0.460
TTK	TACC2	psi-mi:“MI:0403”(colocalization)	0.460
CDCA8	TTK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
TTK	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
TTK	TTK	psi-mi:“MI:0915”(physical association)	0.400
Ttk	TGM1	psi-mi:“MI:0915”(physical association)	0.400
TTK	PRB3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (218): TTK (Affinity Capture-RNA), TTK (Affinity Capture-RNA), TTK (Affinity Capture-Western), TTK (Biochemical Activity), TTK (Affinity Capture-MS), TTK (Affinity Capture-MS), POLR2A (Biochemical Activity), TTK (Affinity Capture-MS), TTK (Proximity Label-MS), TTK (Proximity Label-MS), TTK (Proximity Label-MS), TTK (Proximity Label-MS), TTK (Proximity Label-MS), TTK (Proximity Label-MS), TTK (Proximity Label-MS)

ESM2 similar proteins: A0A1D5PRR9, A4PES0, A4QNA8, D2HHP1, D4A7V9, E1BTE1, E2RSS3, O57473, O75460, P0C1S8, P33279, P33981, P35761, P47817, P54350, Q08D35, Q1LX51, Q20443, Q3UWM4, Q4R8E0, Q4R945, Q4V837, Q5RHD1, Q63185, Q66JT0, Q6DFE0, Q6GPU3, Q6NVF4, Q6P1W0, Q6Z829, Q6ZEZ5, Q8AYG3, Q8AYK6, Q8BMI4, Q8C0Q4, Q8IVT5, Q8L4H0, Q8NG08, Q8NG66, Q8QGV2

Diamond homologs: A2X6X1, A5A7I8, A8WRV1, F1MH24, F1SPM8, F4I4F2, G5ECQ3, O13839, O14976, O34507, O43066, O75716, O77676, O88697, P00516, P00517, P05130, P05132, P0C1X8, P0C605, P17157, P17612, P17948, P25321, P31374, P32023, P33981, P34100, P34331, P35761, P35916, P35917, P35969, P38070, P38080, P40494, P53767, P53974, P54119, P57760

SIGNOR signaling

64 interactions.

A	Effect	B	Mechanism
TTK	up-regulates	CHEK2	phosphorylation
TTK	up-regulates	HSPA9	phosphorylation
TTK	up-regulates	CDCA8	phosphorylation
TTK	up-regulates	TTK	phosphorylation
TTK	down-regulates	TTK	phosphorylation
TTK	down-regulates	ABL1	phosphorylation
CHEK2	unknown	TTK	phosphorylation
TTK	up-regulates	TP53	phosphorylation
1124329-14-1	down-regulates	TTK	“chemical inhibition”
DNA_damage	up-regulates	TTK
CHEK2	up-regulates	TTK	phosphorylation
TTK	“down-regulates quantity by destabilization”	USP16	phosphorylation
TTK	“down-regulates quantity by destabilization”	MAP4	phosphorylation
PLK1	“up-regulates activity”	TTK	phosphorylation
TTK	“up-regulates activity”	BUB1	phosphorylation
TTK	“up-regulates activity”	CENPE	phosphorylation
TTK	“up-regulates activity”	MAPT	phosphorylation
TTK	“up-regulates activity”	MDM2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	12	22.9×	2e-11
Loss of proteins required for interphase microtubule organization from the centrosome	12	22.9×	2e-11
AURKA Activation by TPX2	12	22.0×	2e-11
Anchoring of the basal body to the plasma membrane	15	20.4×	2e-13
Recruitment of mitotic centrosome proteins and complexes	12	19.7×	7e-11
Regulation of PLK1 Activity at G2/M Transition	12	18.4×	1e-10
Recruitment of NuMA to mitotic centrosomes	12	16.9×	3e-10
Cilium Assembly	6	7.9×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	42.7×	2e-07
non-motile cilium assembly	6	14.5×	8e-04
cilium assembly	9	5.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

135 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	98
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2685207	GRCh37/hg19 6q14.1(chr6:79199356-80915988)x1	Pathogenic

SpliceAI

2957 predictions. Top by Δscore:

Variant	Effect	Δscore
6:80005837:CTTAG:C	acceptor_loss	1.0000
6:80005838:TTAGA:T	acceptor_loss	1.0000
6:80005839:TAG:T	acceptor_loss	1.0000
6:80005840:A:AC	acceptor_loss	1.0000
6:80005840:A:AG	acceptor_gain	1.0000
6:80005841:G:GA	acceptor_gain	1.0000
6:80005841:GA:G	acceptor_gain	1.0000
6:80005841:GAA:G	acceptor_gain	1.0000
6:80005841:GAAAT:G	acceptor_gain	1.0000
6:80005979:ACAGG:A	donor_loss	1.0000
6:80005980:CAGGT:C	donor_loss	1.0000
6:80005982:GGT:G	donor_loss	1.0000
6:80005983:G:GG	donor_gain	1.0000
6:80005984:T:A	donor_loss	1.0000
6:80008027:AAAGC:A	donor_gain	1.0000
6:80008028:AAGC:A	donor_gain	1.0000
6:80008029:AGC:A	donor_gain	1.0000
6:80008030:GC:G	donor_gain	1.0000
6:80008030:GCG:G	donor_gain	1.0000
6:80008032:G:GG	donor_gain	1.0000
6:80008033:TA:T	donor_loss	1.0000
6:80008384:A:AG	acceptor_gain	1.0000
6:80008385:G:GG	acceptor_gain	1.0000
6:80008385:GT:G	acceptor_gain	1.0000
6:80010808:T:TA	acceptor_gain	1.0000
6:80010811:TAG:T	acceptor_loss	1.0000
6:80010812:A:AG	acceptor_gain	1.0000
6:80010812:A:G	acceptor_loss	1.0000
6:80010812:AG:A	acceptor_gain	1.0000
6:80010813:G:A	acceptor_loss	1.0000

AlphaMissense

5702 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:80035029:A:C	K553N	1.000
6:80035029:A:T	K553N	1.000
6:80036541:A:C	D664A	1.000
6:80036541:A:T	D664V	1.000
6:80036542:T:A	D664E	1.000
6:80036542:T:G	D664E	1.000
6:80039717:T:A	W718R	1.000
6:80039717:T:C	W718R	1.000
6:80035022:C:A	A551D	0.999
6:80035027:A:C	K553Q	0.999
6:80035027:A:G	K553E	0.999
6:80035028:A:T	K553I	0.999
6:80035375:T:A	W628R	0.999
6:80035375:T:C	W628R	0.999
6:80036490:A:C	D647A	0.999
6:80036490:A:G	D647G	0.999
6:80036490:A:T	D647V	0.999
6:80036493:T:A	L648H	0.999
6:80036493:T:C	L648P	0.999
6:80036506:C:A	N652K	0.999
6:80036506:C:G	N652K	0.999
6:80036508:T:C	F653S	0.999
6:80036535:T:A	L662Q	0.999
6:80036535:T:C	L662P	0.999
6:80036540:G:C	D664H	0.999
6:80036541:A:G	D664G	0.999
6:80039719:G:C	W718C	0.999
6:80039719:G:T	W718C	0.999
6:80040242:T:C	L785P	0.999
6:80031504:T:A	V520D	0.998

dbSNP variants (sampled 300 via entrez): RS1000011676 (6:80015438 A>G), RS1000079763 (6:80016845 A>C), RS1000156218 (6:80039955 A>G), RS1000179964 (6:80034517 C>T), RS1000313266 (6:80041880 C>T), RS1000393536 (6:80028378 C>T), RS1000424087 (6:80034703 A>C,G), RS1000468299 (6:80008240 A>G), RS1000522947 (6:80021703 A>G), RS1000553918 (6:80022019 CTT>C), RS1000597475 (6:80039956 C>A), RS1000700141 (6:80026645 T>A,C), RS1000764627 (6:80028115 C>A,G), RS1000807833 (6:80028322 TTTA>T), RS1000819807 (6:80015530 A>G)

Disease associations

OMIM: gene MIM:604092 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003518_47	Daytime sleep phenotypes	4.000000e-06
GCST006976_68	Macular thickness	6.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3983 (SINGLE PROTEIN), CHEMBL6177901 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193796 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

36 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 371,218 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL3904602	LEROCICLIB	3	1,012
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1721885	SU-014813	2	363
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL215152	DEFOSBARASERTIB	2	372
CHEMBL230011	TG100-115	2	1,504
CHEMBL384304	RG-547	2
CHEMBL402548	DANUSERTIB	2
CHEMBL4303241	BAY-1161909	2
CHEMBL4469414	LUVIXASERTIB	2
CHEMBL475251	R-406	2
CHEMBL513909	BI-2536	2
CHEMBL521851	PICTILISIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL1908397	KW-2449	1
CHEMBL259084	MLN-8054	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — TTK family

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
compound 20 [PMID: 30998356]	Inhibition	9.15	pIC50
luvixasertib	Inhibition	8.77	pIC50
MPI-0479605	Inhibition	8.74	pIC50
compound 27f [PMID: 25625617]	Inhibition	8.55	pIC50
compound 34h [PMID: 27055065]	Inhibition	8.3	pIC50
BAY1217389	Inhibition	8.0	pIC50
empesertib	Inhibition	8.0	pIC50
BOS172722	Inhibition	7.96	pIC50
AZ3146	Inhibition	7.46	pIC50
Ro3280	Inhibition	7.29	pKd
GNE-7915	Inhibition	7.28	pKi
NMS-P715	Inhibition	6.74	pIC50
MPS1-IN-1	Inhibition	6.44	pIC50

Binding affinities (BindingDB)

806 measured of 1082 human assays (1082 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-cyclopropyl-2-methyl-4-[6-pyridin-4-yl-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]benzamide	IC50	0.2 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-4-(oxan-4-ylmethylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.2 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(2-hydroxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.2 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-[(3-fluoro-2-hydroxyphenyl)-hydroxymethyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.2 nM	US-9512126: Substituted imidazopyridazines
4-[6-(2-hydroxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-N,2-dimethylbenzamide	IC50	0.3 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-[1-(3-fluoro-2-hydroxyphenyl)-1-hydroxyethyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.3 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[(2,5-difluorophenyl)-hydroxymethyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.3 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(3-fluorophenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.3 nM	US-9512126: Substituted imidazopyridazines
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
N-cyclopropyl-4-[6-(3-fluorophenoxy)-4-(oxan-4-ylmethylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.4 nM	US-9388140: Substituted benzimidazoles
BDBM236695	IC50	0.4 nM	US-9388140: Substituted benzimidazoles
BDBM236703	IC50	0.4 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(3-fluoro-4-methoxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]benzamide	IC50	0.4 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(3-fluoro-2-hydroxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.4 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-[1-(3-fluoro-4-methoxyphenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.4 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(2,3-difluorophenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.4 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(5-fluoro-2-hydroxyphenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.4 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(5-fluoro-2-hydroxyphenyl)cyclopropyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.4 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-(3-fluoro-4-methoxybenzoyl)-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.4 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-2-methyl-4-[6-phenoxy-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]benzamide	IC50	0.5 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(3-methoxybenzoyl)-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.5 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(4-methoxyphenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.5 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[(2,5-difluorophenyl)-difluoromethyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.5 nM	US-9512126: Substituted imidazopyridazines
US10399974, Example 1	IC50	0.5 nM	US-10399974: N2-phenyl-pyrido[3,4-D]pyrimidine-2, 8-diamine derivatives and their use as Mps1 inhibitors
CHEMBL4873395	KD	0.56 nM
N-cyclopropyl-4-[6-(3-fluoro-5-methylphenoxy)-4-(oxan-4-ylmethylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.6 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(5-fluoro-2-methylphenoxy)-4-(oxan-4-ylmethylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.6 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(3-hydroxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.6 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-[difluoro-(3-fluoro-4-methoxyphenyl)methyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.6 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-(2,5-difluorobenzoyl)-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.6 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-(2,3-difluorobenzoyl)-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.6 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(2,5-difluorophenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.6 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[difluoro-(4-methoxyphenyl)methyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.6 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-(3-fluorophenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.7 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(3-fluoro-4-methoxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.7 nM	US-9388140: Substituted benzimidazoles
N-ethyl-4-[6-(2-hydroxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.7 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(3-fluoro-4-hydroxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.7 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-(3-fluoro-4-hydroxyphenoxy)-4-(oxan-4-ylmethylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.7 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-[fluoro-(3-fluorophenyl)methyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.7 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[difluoro-(3-fluorophenyl)methyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.7 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(2,3-difluorophenyl)cyclopropyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.7 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(3-methoxyphenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.8 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-[1-(2,5-difluorophenyl)cyclopropyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.8 nM	US-9512126: Substituted imidazopyridazines
N-cyclopropyl-4-[6-(2-fluoro-4-methoxyphenoxy)-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.9 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-7-(3,3,3-trifluoropropylamino)benzimidazol-5-yl]-2-methylbenzamide	IC50	0.9 nM	US-9388140: Substituted benzimidazoles
4-[3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-7-(3,3,3-trifluoropropylamino)benzimidazol-5-yl]-N,2-dimethylbenzamide	IC50	0.9 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-[(3-fluoro-4-methoxyphenyl)methyl]-4-(3,3,3-trifluoropropylamino)benzimidazol-1-yl]-2-methylbenzamide	IC50	0.9 nM	US-9388140: Substituted benzimidazoles
N-cyclopropyl-4-[6-[1-(3-fluorophenyl)cyclopropyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	IC50	0.9 nM	US-9512126: Substituted imidazopyridazines
4-[6-(5-cyanopent-1-ynyl)-8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylbenzamide	IC50	1 nM	US-9199999: Substituted imidazopyrazines
N-cyclopropyl-4-[6-(4-cyclopropylsulfinylphenyl)-8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-3-yl]benzamide	IC50	1 nM	US-9284317: Substituted imidazo[1,2-a]pyrazines as MPS-1 inhibitors

ChEMBL bioactivities

2238 potent at pChembl≥5 of 2282 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.33	Ki	0.047	nM	CHEMBL4249882
10.15	Kd	0.071	nM	CHEMBL4877547
10.08	Ki	0.084	nM	CHEMBL3911532
10.06	Ki	0.088	nM	CHEMBL4245639
10.03	Ki	0.094	nM	CHEMBL3927553
10.00	Ki	0.1	nM	LUVIXASERTIB
10.00	IC50	0.1	nM	CHEMBL4632740
9.96	Ki	0.11	nM	CHEMBL4239476
9.96	Ki	0.11	nM	BOS-172722
9.92	Ki	0.12	nM	CHEMBL4247121
9.92	Ki	0.12	nM	CHEMBL4240502
9.92	Kd	0.12	nM	CHEMBL4845775
9.89	Ki	0.13	nM	CHEMBL3932996
9.82	IC50	0.15	nM	CHEMBL4636046
9.82	Kd	0.15	nM	CHEMBL4875028
9.77	Kd	0.17	nM	CHEMBL4870223
9.77	Kd	0.17	nM	CHEMBL4858486
9.72	Ki	0.19	nM	CHEMBL4251352
9.70	Ki	0.2	nM	CHEMBL3809829
9.70	IC50	0.2	nM	CHEMBL3951371
9.70	IC50	0.2	nM	CHEMBL3928754
9.70	IC50	0.2	nM	CHEMBL3961628
9.70	Ki	0.2	nM	CHEMBL4249151
9.70	IC50	0.2	nM	CHEMBL4638914
9.70	IC50	0.2	nM	CHEMBL4642174
9.70	Kd	0.2	nM	CHEMBL4846040
9.60	IC50	0.25	nM	BAY-1217389
9.54	Kd	0.29	nM	CHEMBL4869527
9.52	IC50	0.3	nM	CHEMBL3354568
9.52	IC50	0.3	nM	CHEMBL3410078
9.52	IC50	0.3	nM	CHEMBL3965128
9.52	IC50	0.3	nM	CHEMBL4632416
9.52	IC50	0.3	nM	CHEMBL4645348
9.52	Kd	0.3	nM	CHEMBL4868353
9.47	IC50	0.34	nM	BAY-1161909
9.42	Ki	0.38	nM	CHEMBL4250961
9.40	IC50	0.4	nM	CHEMBL3354567
9.40	IC50	0.4	nM	CHEMBL3818646
9.40	IC50	0.4	nM	CHEMBL3932181
9.40	IC50	0.4	nM	CHEMBL3912382
9.40	IC50	0.4	nM	CHEMBL3941964
9.40	IC50	0.4	nM	CHEMBL3923628
9.40	IC50	0.4	nM	CHEMBL3918586
9.40	IC50	0.4	nM	CHEMBL4640247
9.39	Kd	0.41	nM	CHEMBL4860430
9.39	Kd	0.41	nM	CHEMBL4866294
9.39	IC50	0.41	nM	CHEMBL5830301
9.39	IC50	0.41	nM	CHEMBL6018982
9.37	IC50	0.43	nM	CHEMBL5401292
9.37	IC50	0.43	nM	CHEMBL5801593

PubChem BioAssay actives

964 with measured affinity, of 1682 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-N-[(2S)-3,3-dimethylbutan-2-yl]-2-N-[2-ethoxy-4-(4-methyl-1,2,4-triazol-3-yl)phenyl]-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	<0.0001	uM
N-cyclopropyl-4-[7-[(3-hydroxy-3-methylcyclobutyl)methylamino]-5-pyridin-3-yloxypyrazolo[1,5-a]pyrimidin-3-yl]-2-methylbenzamide	1627435: Inhibition of full length recombinant N-terminal GST-tagged and sumo-tagged human TTK (1 to 275 residues) expressed in Escherichia coli pre-incubated for 5 mins before ATP addition by indirect ELISA	ki	0.0001	uM
N-[2-ethoxy-4-(4-methyl-1,2,4-triazol-3-yl)phenyl]-6-methyl-8-(7-oxa-2-azaspiro[3.5]nonan-2-yl)pyrido[3,4-d]pyrimidin-2-amine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
8-(3,3-dimethylazetidin-1-yl)-N-[2-ethoxy-4-(4-methyl-1,2,4-triazol-3-yl)phenyl]-6-methylpyrido[3,4-d]pyrimidin-2-amine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
8-N-(2,2-dimethylpropyl)-2-N-[4-(4,5-dimethyl-1,2,4-triazol-3-yl)-2-ethoxyphenyl]-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
2-N-[4-[5-[2-(dimethylamino)ethyl]-4-methyl-1,2,4-triazol-3-yl]-2-ethoxyphenyl]-8-N-(2,2-dimethylpropyl)-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]cyclopentanecarboxamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0001	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]cyclohexanecarboxamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0001	uM
N-cyclopropyl-4-[7-[2-(3-hydroxy-3-methylcyclobutyl)ethyl]-5-pyridin-3-yloxypyrazolo[1,5-a]pyrimidin-3-yl]-2-methylbenzamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0001	uM
2-(4-fluorophenyl)-N-[4-[2-[2-methoxy-4-(2-oxa-6-azaspiro[3.3]heptane-6-carbonyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]acetamide	1660100: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
2-(4-fluorophenyl)-N-[4-[2-[2-methoxy-4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl]anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]acetamide	1660100: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
8-N-(2,2-dimethylpropyl)-2-N-[2-ethoxy-4-(4-methyl-1,2,4-triazol-3-yl)phenyl]-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
2-N-[4-(2,3-dimethylimidazol-4-yl)-2-methoxyphenyl]-8-N-(2,2-dimethylpropyl)-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
8-N-(2,2-dimethylpropyl)-2-N-[2-methoxy-4-(4-methyl-1,2,4-triazol-3-yl)phenyl]-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
2-N-[4-(2,3-dimethylimidazol-4-yl)-2-methoxyphenyl]-8-N-(2,2-dimethylpropyl)pyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0001	uM
1-[2-[2-ethoxy-4-(4-methyl-1,2,4-triazol-3-yl)anilino]-6-methylpyrido[3,4-d]pyrimidin-8-yl]-3-methylazetidine-3-carbonitrile	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0002	uM
2-N-[4-(6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)-2-methoxyphenyl]-8-N-(2,2-dimethylpropyl)-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0002	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]-2,2-dimethylpropanamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0002	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]cyclohexanecarboxamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0002	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]cyclopentanecarboxamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0002	uM
2-(4-fluorophenyl)-N-[4-[2-[4-(morpholine-4-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]acetamide	1660100: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0002	uM
4-[6-benzyl-8-(3,3,3-trifluoropropylamino)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropyl-2-methylbenzamide	1660099: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 10 uM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0002	uM
8-N-[(2S)-3,3-dimethylbutan-2-yl]-2-N-[2-methoxy-4-(1-methylpyrazol-4-yl)phenyl]pyrido[3,4-d]pyrimidine-2,8-diamine	1302308: Inhibition of human full length MPS1 expressed in recombinant baculovirus infected Sf9 insect cells using 5FAM-DHTGFLTEYVATRCONH2 as substrate after 60 to 90 mins in presence of 1 mM ATP	ki	0.0002	uM
N-cyclopropyl-4-[6-(2-hydroxyphenoxy)-8-(oxan-4-ylmethylamino)imidazo[1,2-b]pyridazin-3-yl]benzamide	1197787: Inhibition of FLAG-tagged Mps1 autophosphorylation in human RERF-LC-AI cells expressing Tet-suppressible promotor after 3 hrs by immunoblotting	ic50	0.0003	uM
N-cyclopropyl-4-[8-[(3-hydroxy-3-methylcyclobutyl)methylamino]-6-pyridin-3-yloxyimidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	1660100: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0003	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]benzamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0003	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]propanamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0003	uM
(2R)-2-(4-fluorophenyl)-N-[4-[2-(2-methoxy-4-methylsulfonylanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]propanamide	1552062: Inhibition of MPS1 (unknown origin) using biotin-AhxPWDPDDADITEILG-NH2 as substrate preincubated for 15 mins followed by substrate addition by TR-FRET assay	ic50	0.0003	uM
N-cyclopropyl-4-[6-[1-(3-fluoro-4-methoxyphenyl)ethenyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	1660101: Inhibition of MPS1 in human HeLa cells assessed as reduction in spindle assembly checkpoint incubated for 4 hrs by p-histone H3/Hoechst 33342 staining based microscopic analysis	ic50	0.0003	uM
N-cyclopropyl-4-[6-[1-(3-fluoro-2-hydroxyphenyl)-1-hydroxyethyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	1177105: Inhibition of Mps1 (unknown origin) activity by TR-FRET assay	ic50	0.0003	uM
N-cyclopropyl-4-[6-(2,3-difluoro-4-methoxyphenoxy)-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	1660101: Inhibition of MPS1 in human HeLa cells assessed as reduction in spindle assembly checkpoint incubated for 4 hrs by p-histone H3/Hoechst 33342 staining based microscopic analysis	ic50	0.0003	uM
2-N-[4-(6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)-2-ethoxyphenyl]-8-N-(2,2-dimethylpropyl)-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0004	uM
N-cyclopropyl-4-[5-(2,3-difluoro-4-methoxyphenoxy)-7-(3,3,3-trifluoropropylamino)pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylbenzamide	1660101: Inhibition of MPS1 in human HeLa cells assessed as reduction in spindle assembly checkpoint incubated for 4 hrs by p-histone H3/Hoechst 33342 staining based microscopic analysis	ic50	0.0004	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]cyclopropanecarboxamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0004	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]propanamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0004	uM
N-cyclopropyl-4-[6-(3-fluoro-4-methoxybenzoyl)-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	1177105: Inhibition of Mps1 (unknown origin) activity by TR-FRET assay	ic50	0.0004	uM
8-N-(2,2-dimethylpropyl)-2-N-[2-methoxy-4-(1-methylpyrazol-4-yl)phenyl]pyrido[3,4-d]pyrimidine-2,8-diamine	1400289: Inhibition of full length human N-terminal 6xHis-tagged MPS1 expressed in baculovirus expression system using 5FAM-H236 peptide as substrate after 60 to 90 mins by caliper assay	ki	0.0004	uM
N-cyclopropyl-4-[2-(2,3-difluorophenoxy)-4-(oxan-4-ylmethylamino)pyrazolo[1,5-a][1,3,5]triazin-8-yl]-2-methylbenzamide	1309251: Inhibition of TTK (unknown origin)	ic50	0.0004	uM
4-[(1-hydroxy-2-methylpropan-2-yl)amino]-2-[(2-methyl-6-morpholin-4-yl-3-pyridinyl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	1552063: Inhibition of MPS1 (510 to 857 residues) catalytic domain (unknown origin) expressed in Escherichia coli after 15 mins by mass-spectrometry analysis	ki	0.0005	uM
2-[(2-methyl-6-morpholin-4-yl-3-pyridinyl)amino]-4-(oxan-4-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	1552063: Inhibition of MPS1 (510 to 857 residues) catalytic domain (unknown origin) expressed in Escherichia coli after 15 mins by mass-spectrometry analysis	ki	0.0005	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]-2-methylpropanamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0005	uM
N-cyclopropyl-2-methyl-4-[6-phenoxy-8-(3,3,3-trifluoropropylamino)imidazo[1,2-a]pyrazin-3-yl]benzamide	1660099: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 10 uM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0005	uM
(2R)-N-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)propanamide	1660100: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0005	uM
N-(2,6-diethylphenyl)-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5,6-dihydropyrimido[4,5-e]indolizine-7-carboxamide	1924156: Inhibition of human TTK by TR-FRET assay	ic50	0.0006	uM
4-[[4-(4-hydroxy-4-methylcyclohexyl)oxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N,N-dimethylbenzamide	1551587: Inhibition of Kinase Tracer 236 binding to recombinant human full-length GST-tagged TTk expressed in baculovirus expression system measured after 1 hr by LanthaScreen Eu–kinase binding assay	ic50	0.0006	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]adamantane-1-carboxamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0006	uM
N-[4-[5-methyl-2-[2-methyl-4-(4-methylpiperazin-1-yl)anilino]-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]propanamide	1760717: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method	kd	0.0006	uM
N-cyclopropyl-4-[6-[difluoro-(4-methoxyphenyl)methyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	1177105: Inhibition of Mps1 (unknown origin) activity by TR-FRET assay	ic50	0.0006	uM
N-cyclopropyl-4-[6-[1-(5-fluoro-2-hydroxyphenyl)cyclopropyl]-8-(3,3,3-trifluoropropylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide	1660099: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 10 uM ATP addition and measured after 60 mins by TR-FRET assay	ic50	0.0006	uM
N-[(R)-cyclopropyl(pyridin-2-yl)methyl]-3-[4-[(1S,5S)-3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl]phenyl]-1H-indazole-5-carboxamide	1203320: Competitive inhibition of amino terminal GST-fused full length human TTK using His6-SUMO-TTK-N as substrate by Lineweaver-Burk plot analysis in presence of ATP	ki	0.0007	uM

CTD chemical–gene interactions

96 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	5
Acetaminophen	decreases expression, increases expression	3
Estradiol	increases expression	3
Valproic Acid	decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Testosterone	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
methylselenic acid	decreases expression	1
kojic acid	decreases expression	1
beta-lapachone	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
cryptolepine	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1

ChEMBL screening assays

505 unique, capped per target: 473 binding, 32 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1021461	Binding	Inhibition of TTK assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem
CHEMBL5444952	Functional	Affinity Phenotypic Cellular interaction: (Immunoblot activity assay (using LAP-Mps1 WT in U2OS cells)) EUB0000608a TTK	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.