TPX2

Summary

TPX2 (TPX2 microtubule nucleation factor, HGNC:1249) is a protein-coding gene on chromosome 20q11.21, encoding Targeting protein for Xklp2 (Q9ULW0). Spindle assembly factor required for normal assembly of mitotic spindles. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Enables several functions, including importin-alpha family protein binding activity; protein kinase binding activity; and protein serine/threonine kinase activator activity. Involved in activation of protein kinase activity; microtubule cytoskeleton organization; and negative regulation of microtubule depolymerization. Located in intercellular bridge; nucleoplasm; and spindle. Is active in spindle.

Source: NCBI Gene 22974 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 119 total
• GTEx eGene: eQTL in 17 tissues, sQTL in 2 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.29 (highly constrained)
• MANE Select transcript: NM_012112
• Notable: 119 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1249
Approved symbol	TPX2
Name	TPX2 microtubule nucleation factor
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	p100, DIL-2, HCA519, FLS353
Ensembl gene	ENSG00000088325
Ensembl biotype	protein_coding
OMIM	605917
Entrez	22974

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 34 protein_coding, 2 nonsense_mediated_decay

MANE Select: ENST00000300403

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000300403, ENST00000340513, ENST00000853939, ENST00000853940, ENST00000853941, ENST00000853942, ENST00000853943, ENST00000853944, ENST00000853945, ENST00000853946, ENST00000853947, ENST00000853948, ENST00000853949, ENST00000853950, ENST00000853951, ENST00000853952, ENST00000853953, ENST00000934050, ENST00000934051, ENST00000934052, ENST00000934053, ENST00000934054, ENST00000934055, ENST00000934056, ENST00000934057, ENST00000934058, ENST00000934059, ENST00000934060, ENST00000934061, ENST00000934062, ENST00000934063, ENST00000934064, ENST00000934065, ENST00001081795, ENST00001081796, ENST00001131925

RefSeq mRNA: 1 — MANE Select: NM_012112 NM_012112

CCDS: CCDS13190

Canonical transcript exons

ENST00000300403 — 18 exons

Exon	Start	End
ENSE00000560794	31760057	31760179
ENSE00000560800	31778813	31778984
ENSE00000560807	31798365	31798552
ENSE00000661090	31766556	31766682
ENSE00000661091	31770343	31770471
ENSE00000661092	31771560	31771682
ENSE00000661094	31775867	31775988
ENSE00000661095	31777487	31777638
ENSE00000661097	31782249	31782390
ENSE00000661098	31783705	31783921
ENSE00000661099	31792735	31792830
ENSE00000661100	31793848	31794024
ENSE00000661101	31794402	31794548
ENSE00000661102	31797404	31797515
ENSE00000859866	31757407	31757582
ENSE00001388212	31742541	31742647
ENSE00003848934	31739290	31739621
ENSE00003849573	31800970	31801800

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3123 / max 509.6753, expressed in 1634 samples.

Highest expression (Bgee): ventricular zone, ganglionic eminence, embryo, endometrium epithelium, oocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TPX2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	4.1e-18	+0.36	20:31751342:C:G
Adipose Subcutaneous	eqtl	3.6e-12	+0.25	20:31751342:C:G
Skin Sun Exposed Lower leg	eqtl	1.3e-11	+0.16	20:31698388:A:G
Adipose Visceral Omentum	eqtl	2.1e-09	+0.24	20:31751342:C:G
Testis	eqtl	7.7e-08	-0.16	20:31771091:G:C
Breast Mammary Tissue	eqtl	2.9e-06	+0.23	20:31751342:C:G
Heart Atrial Appendage	eqtl	3.4e-06	+0.29	20:31751342:C:G
Skin Not Sun Exposed Suprapubic	eqtl	7.8e-05	+0.10	20:31698388:A:G
Skin Sun Exposed Lower leg	sqtl	8.0e-05	-0.32	20:31698388:A:G
Cells EBV-transformed lymphocytes	sqtl	6.2e-04	-0.52	20:31736242:C:T
Brain Cerebellum	eqtl	7.3e-03	+0.25	20:31930765:G:A
Heart Left Ventricle	eqtl	1.2e-02	+0.21	20:31751342:C:G
Artery Tibial	eqtl	1.9e-02	+0.23	20:31763183:A:G
Whole Blood	eqtl	2.1e-02	-0.08	20:31922842:T:G
Artery Aorta	eqtl	3.1e-02	+0.19	20:32511508:T:C
Esophagus Muscularis	eqtl	3.2e-02	+0.66	20:32169713:C:G
Colon Transverse	eqtl	4.0e-02	-0.23	20:31919993:G:A
Adrenal Gland	eqtl	4.5e-02	-0.46	20:32390386:C:T
Lung	eqtl	4.5e-02	+0.09	20:31751342:C:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
183981	45.4156	1623
183982	1.6602	772
209071	0.1799	80
183984	0.0492	19
183985	0.0073	4

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.79	gold quality
ganglionic eminence	UBERON:0004023	96.63	gold quality
embryo	UBERON:0000922	96.29	gold quality
endometrium epithelium	UBERON:0004811	94.57	gold quality
oocyte	CL:0000023	94.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.46	gold quality
secondary oocyte	CL:0000655	92.76	gold quality
bone marrow	UBERON:0002371	88.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.45	gold quality
trabecular bone tissue	UBERON:0002483	87.59	gold quality
bone element	UBERON:0001474	86.89	gold quality
right testis	UBERON:0004534	86.72	gold quality
left testis	UBERON:0004533	86.46	gold quality
bone marrow cell	CL:0002092	86.44	gold quality
testis	UBERON:0000473	86.31	gold quality
mucosa of transverse colon	UBERON:0004991	86.16	gold quality
thymus	UBERON:0002370	85.75	gold quality
stromal cell of endometrium	CL:0002255	85.69	gold quality
rectum	UBERON:0001052	83.78	gold quality
vermiform appendix	UBERON:0001154	82.17	gold quality
ileal mucosa	UBERON:0000331	82.08	silver quality
sperm	CL:0000019	81.48	silver quality
esophagus mucosa	UBERON:0002469	81.19	gold quality
male germ cell	CL:0000015	80.85	silver quality
lower esophagus mucosa	UBERON:0035834	79.87	gold quality
adrenal tissue	UBERON:0018303	79.41	gold quality
caecum	UBERON:0001153	78.30	gold quality
cartilage tissue	UBERON:0002418	77.98	gold quality
lymph node	UBERON:0000029	77.62	gold quality
tongue squamous epithelium	UBERON:0006919	77.41	gold quality
oral cavity	UBERON:0000167	76.57	gold quality
epithelium of esophagus	UBERON:0001976	75.22	gold quality
esophagus squamous epithelium	UBERON:0006920	74.45	gold quality
epithelium of nasopharynx	UBERON:0001951	74.23	silver quality
smooth muscle tissue	UBERON:0001135	74.11	gold quality
skin of leg	UBERON:0001511	73.88	gold quality
squamous epithelium	UBERON:0006914	73.75	silver quality
endometrium	UBERON:0001295	73.23	gold quality
colonic epithelium	UBERON:0000397	73.14	gold quality
skin of abdomen	UBERON:0001416	72.74	gold quality
gingival epithelium	UBERON:0001949	72.57	silver quality
placenta	UBERON:0001987	72.43	gold quality
cortical plate	UBERON:0005343	72.38	gold quality
colonic mucosa	UBERON:0000317	72.16	gold quality
tonsil	UBERON:0002372	72.01	gold quality
zone of skin	UBERON:0000014	71.72	gold quality
mucosa of sigmoid colon	UBERON:0004993	71.48	gold quality
transverse colon	UBERON:0001157	71.36	gold quality
gingiva	UBERON:0001828	71.10	silver quality
duodenum	UBERON:0002114	69.85	gold quality
spleen	UBERON:0002106	69.82	gold quality
adult organism	UBERON:0007023	69.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.94	gold quality
small intestine	UBERON:0002108	68.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.26	gold quality
cervix squamous epithelium	UBERON:0006922	68.10	gold quality
islet of Langerhans	UBERON:0000006	67.87	gold quality
amniotic fluid	UBERON:0000173	67.55	gold quality
right coronary artery	UBERON:0001625	67.11	gold quality
esophagus	UBERON:0001043	66.79	gold quality
hair follicle	UBERON:0002073	66.65	gold quality
right adrenal gland	UBERON:0001233	66.62	gold quality
right adrenal gland cortex	UBERON:0035827	66.42	gold quality
intestine	UBERON:0000160	66.28	gold quality
gall bladder	UBERON:0002110	66.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	65.88	gold quality
upper leg skin	UBERON:0004262	65.45	gold quality
vagina	UBERON:0000996	65.11	gold quality
prefrontal cortex	UBERON:0000451	65.07	gold quality
large intestine	UBERON:0000059	65.03	gold quality
gastrocnemius	UBERON:0001388	64.82	gold quality
upper arm skin	UBERON:0004263	64.67	gold quality
colon	UBERON:0001155	64.48	gold quality
muscle of leg	UBERON:0001383	64.40	gold quality
descending thoracic aorta	UBERON:0002345	64.09	gold quality
right lobe of liver	UBERON:0001114	64.04	gold quality
frontal pole	UBERON:0002795	64.03	gold quality
middle frontal gyrus	UBERON:0002702	63.92	gold quality
paraflocculus	UBERON:0005351	63.73	gold quality
left adrenal gland	UBERON:0001234	63.71	gold quality
adrenal gland	UBERON:0002369	63.58	gold quality
jejunal mucosa	UBERON:0000399	63.45	gold quality
left coronary artery	UBERON:0001626	63.05	gold quality
stomach	UBERON:0000945	63.01	gold quality
body of stomach	UBERON:0001161	62.86	gold quality
skin of hip	UBERON:0001554	62.70	silver quality
oviduct epithelium	UBERON:0004804	62.42	silver quality
uterus	UBERON:0000995	62.15	gold quality
coronary artery	UBERON:0001621	62.13	gold quality
left adrenal gland cortex	UBERON:0035825	61.73	gold quality
liver	UBERON:0002107	61.65	gold quality
granulocyte	CL:0000094	61.38	gold quality
blood	UBERON:0000178	61.20	gold quality
thoracic aorta	UBERON:0001515	61.16	gold quality
adrenal cortex	UBERON:0001235	61.14	gold quality
aorta	UBERON:0000947	60.94	gold quality
ascending aorta	UBERON:0001496	60.94	gold quality
popliteal artery	UBERON:0002250	60.93	gold quality
tibial artery	UBERON:0007610	60.91	gold quality
muscle organ	UBERON:0001630	60.83	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1430.50
E-MTAB-8559	yes	1100.01
E-MTAB-10485	yes	1044.63
E-ENAD-20	yes	867.92
E-GEOD-93593	yes	865.60
E-MTAB-8894	yes	784.79
E-MTAB-10290	yes	608.80
E-MTAB-7249	yes	525.43
E-MTAB-8271	yes	522.74
E-MTAB-7052	yes	396.33
E-MTAB-8530	yes	221.67
E-HCAD-10	yes	36.38
E-HCAD-13	yes	23.55
E-HCAD-6	yes	21.13
E-HCAD-5	yes	18.81

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	65.5
Bone marrow	tissue	45.3	high
Tonsil	tissue	30.3
Testis	tissue	28.7	low
Lymph node	tissue	24.8	low
Rectum	tissue	13.4	medium
Appendix	tissue	12.3	medium
Colon	tissue	10.9	medium
Skin 1	tissue	9.3	medium
Duodenum	tissue	8.9	medium
Small intestine	tissue	8.8	low
Placenta	tissue	7.8	medium
Esophagus	tissue	7.3	medium
Smooth muscle	tissue	6.3	low
Stomach 1	tissue	5.8	high
Hippocampal formation	tissue	5.2
Cerebral cortex	tissue	5.0	medium
Occipital cortex	tissue	5.0
Pons	tissue	4.6
Entorhinal cortex	tissue	4.6
Temporal cortex	tissue	4.6
Prefrontal cortex	tissue	4.5
Thalamus	tissue	4.5
Cerebellum	tissue	4.5	medium
Somatosensory cortex	tissue	4.5
Superior colliculi	tissue	4.4
Retrosplenial and cingulate cortex	tissue	4.4
Olfactory bulb	tissue	4.4
Amygdala	tissue	4.3
Midbrain	tissue	4.3
Motor cortex	tissue	4.2
Basal ganglia	tissue	4.2	medium
Periaqueductal gray	tissue	4.1
Vagina	tissue	4.0	medium
Hypothalamus	tissue	4.0
Liver	tissue	4.0	low
Insular cortex	tissue	4.0
Retrosplenial cortex	tissue	3.8
Substantia nigra	tissue	3.7
Spleen	tissue	3.7	not detected
Spinal cord	tissue	3.6
Ventral forebrain	tissue	3.6
Septum	tissue	3.6
Medulla oblongata	tissue	3.5
Corpus callosum	tissue	3.5
Putamen	tissue	3.4
Urinary bladder	tissue	3.2	medium
Caudate putamen	tissue	2.8
Ovary	tissue	2.7	not detected
Breast	tissue	2.5	medium
Endometrium 1	tissue	2.2	medium
Postcentral gyrus	tissue	2.0
Adipose tissue	tissue	1.8	not detected
Frontal cortex	tissue	1.8
Nucleus accumbens	tissue	1.8
Gallbladder	tissue	1.6	low
Cervix	tissue	1.4	medium
Lung	tissue	1.4	medium
Choroid plexus	tissue	1.3
Skeletal muscle	tissue	1.2	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral hippocampus (5.2), Dorsal hippocampus (4.7), Subiculum (4.7), Dorsal spinal cord (3.6), White matter (3.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

Targeting TPX2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

28 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-8069	97.05	66.79	718
HSA-MIR-759	96.16	66.77	873

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.29, missense Z 1.49 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000300403 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
20:31,757,477–31,760,110	36 / 58.3	0.62	no
20:31,760,111–31,777,593	279 / 261.6	1.07	no
20:31,777,594–31,801,077	461 / 551.2	0.84	no
DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): G-292, clone A141B1 (-2.649), EC-GI-10 (-2.581), RERF-GC-1B (-2.469), MHH-NB-11 (-2.447), SNU-1196 (-2.38), NB-4 (-2.372), DB (-2.344), AU565 (-2.327), VCaP (-2.324), OE33 (-2.278), PC-14 (-2.259), ZR-75-1 (-2.175), KP-2 (-2.142), SK-N-FI (-2.127), HCC38 (-2.117).

Literature-anchored findings (GeneRIF, showing 40)

• TPX2 is required for targeting Aurora-A kinase to the spindle apparatus and Aurora-A might regulate the function of TPX2 during spindle assembly (PMID:12177045)
• spindle formation requires the function of TPX2 to generate a stable bipolar spindle with overlapping antiparallel microtubule arrays (PMID:12389033)
• observations reveal a structural role for hTPX2 in spindles and provide evidence for a balance between microtubule-based motor forces and structural spindle components (PMID:12477396)
• molecular cloning; overexpression provokes accumulation of cells in G(2)-M phase and subsequent polyploidization, suggesting that excess repp86 may interfere with correct nuclear division (PMID:12612055)
• APC/C(Cdh1) controls the stability of TPX2, thereby ensuring accurate regulation of the spindle assembly in the cell cycle (PMID:16287863)
• Aberrant expression of TPX2 may play important role(s) in both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer and could serve as a prognostic predictor for the disease. (PMID:16489064)
• TPX2 binding decreases the size and accessibility of a hydrophobic pocket, adjacent to the ATP site, to inhibitors. (PMID:17705509)
• Data show that Siah2 is an important mediator of repp86 protein degradation. (PMID:17716627)
• Chromosome nucleation is involved in spindle pole separation and setting spindle length. A second Aurora A-independent function of TPX2 is required to bipolarize spindles. (PMID:18663142)
• human TPX2 mRNA is closely linked to increased or abnormal cell proliferation in malignant salivary gland tumors. (PMID:19148505)
• Data provide a molecular explanation for the assembly of the apoptotic microtubule network, and suggest important similarities with the process of RanGTP- and TPX2-mediated mitotic spindle formation. (PMID:19208764)
• Overexpression of TPX2 is associated with oral squamous cell carcinomas. (PMID:19424574)
• Data show that Aurora A(S155R) mutant reduced cellular activity and mislocalization are due to loss of interaction with TPX2. (PMID:19801554)
• TPX2 expression is associated with the progression of malignant astrocytoma. (PMID:20599806)
• association of Aurora-A and TPX2 gives rise to a novel functional unit with oncogenic properties.[review] (PMID:20708655)
• Decreased AurA-TPX2 complex formation in response to irradiation results from reduced cellular levels of TPX2, as a result of protein degradation and decreased translation of TPX2 mRNA. (PMID:21099343)
• TPX2 protects Aurora-A from degradation both in interphase and in mitosis. (PMID:21147853)
• Results demonstrate a role for PP6 as the T-loop phosphatase regulating Aurora A activity bound to its activator TPX2 during mitotic spindle formation. (PMID:21187329)
• two switches determining Aurora A activation (PMID:21347367)
• TPX2 promote 20q amplicon-driven progression of colorectal adenoma to carcinoma. (PMID:22207630)
• TPX2 shows potential to be used as a new marker for cervical cancer diagnosis and therapy. (PMID:22307108)
• The data support the role of TPX2 as a novel co-activator of Aurora kinase B. (PMID:22560880)
• AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression (PMID:22761906)
• the regulation of gamma-H2AX signals by TPX2 is not associated with apoptosis or the mitotic functions of TPX2. (PMID:23045526)
• Data indicate that the sensitivity of cell-lines with amplification of AURKA depends upon the activity of the kinase, which correlates with the expression of the regulatory gene products TPX2 and HMMR/RHAMM. (PMID:23328114)
• GLIPR1 interacts with Hsc70, and GLIPR1 overexpression or Hsc70 knockdown leads to transcriptional suppression of AURKA and TPX2. (PMID:23333597)
• Data indicate that expression-based risk indices of three genes UBE2C, TPX2, and MELK were more strongly associated with poor 5-year survival in adenocarcinoma patients. (PMID:23357462)
• Data show that five genes CKAP5, KPNB1, RAN, TPX2 and KIF11 were shown to be essential for tumor cell survival in both head and neck squamous cell carcinoma (HNSCC)and non-small cell lung cancer (NSCLC), but most particularly in HNSCC. (PMID:23444224)
• The expression of TPX2 protein and mRNA were correlated with invasive depth and lymphatic metastasis of esophageal squamous cell carcinoma. (PMID:23725757)
• Data indicate that TPX2 (target protein for Xklp2) may play a role in the development and progression of bladder carcinoma, and suggest that inhibition of TPX2 level may be a novel strategy for therapy of the patients with bladder carcinoma. (PMID:23873098)
• TPX2 expression is associated with cell proliferation and poor prognosis among patients with resected esophageal squamous cell carcinoma (PMID:23963785)
• TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer, and may represent a novel prognostic biomarker and therapeutic target for the disease (PMID:24341487)
• TPX2 overexpression is associated with medullary thyroid carcinoma. (PMID:24488334)
• This review provides an historic overview of the discovery of TPX2 and summarizes its cytoskeletal and signaling roles with relevance to cancer therapies. [review] (PMID:24556998)
• RAN nucleo-cytoplasmic transport and mitotic spindle assembly partners XPO7 and TPX2 have roles in serous epithelial ovarian cancer (PMID:24625450)
• The results demonstrated that TPX2 is important in the regulation of tumor growth in cervical cancer and therefore may be a potential therapeutic target as a novel treatment strategy. (PMID:24718984)
• the molecular mechanisms of two distinct activation strategies (autophosphorylation and TPX2-mediated activation) in human Aurora A kinase, was elucidated. (PMID:24867643)
• Identify RHAMM as a critical regulator of TPX2 location/ Aurora kinase A signaling and suggest that RHAMM ensures bipolar spindle assembly and mitotic progression through the integration of biochemical and structural pathways. (PMID:24875404)
• TPX2 siRNA transfection significantly reduced tumor growth. (PMID:25239289)
• In vitro studies found that TPX2 knockdown significantly inhibited cell proliferation and viability in both Hep3B and HepG2 cells. (PMID:25302620)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpx2	ENSDARG00000078654
mus_musculus	Tpx2	ENSMUSG00000027469
rattus_norvegicus	Tpx2	ENSRNOG00000008165

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919369) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased cell proliferation	1
increased metastatic potential	1
abnormal embryo development	1
embryonic growth arrest	1
increased lung adenocarcinoma incidence	1
increased lung adenoma incidence	1
increased intestinal adenoma incidence	1
granulomatous inflammation	1
abnormal cell nucleus morphology	1
increased hepatocellular carcinoma incidence	1
aneuploidy	1
polyploidy	1
abnormal mitosis	1
pituitary intermediate lobe hyperplasia	1
abnormal splenocyte morphology	1
abnormal mitotic spindle morphology	1
abnormal mitotic spindle assembly checkpoint	1
increased stomach tumor incidence	1
embryonic lethality, complete penetrance	1
preweaning lethality, complete penetrance	1
increased lymphoma incidence	1
embryonic lethality prior to organogenesis	1
increased micronucleus incidence	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RAF2	90.1%	Diamond
Xenopus laevis	Q6DDV8	87.0%	Diamond
Bos taurus	A6H6Z7	81.3%	Diamond
Xenopus tropicalis	A4IH24	76.5%	Diamond
Patiria pectinifera	E2RYF8	39.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
BCL2L1	protein-coding	598
COX4I2	protein-coding	84701
MIR3193	ncRNA	100422904
BCL2L1-AS1	ncRNA	105372589
MYLK2	protein-coding	85366
DUSP15	protein-coding	128853
FOXS1	protein-coding	2307
TTLL9	protein-coding	164395

Protein

Protein identifiers

Targeting protein for Xklp2 — Q9ULW0 (reviewed: Q9ULW0)

Alternative names: Differentially expressed in cancerous and non-cancerous lung cells 2, Hepatocellular carcinoma-associated antigen 519, Hepatocellular carcinoma-associated antigen 90, Protein fls353, Restricted expression proliferation-associated protein 100

All UniProt accessions (2): Q9ULW0, Q643R0

UniProt curated annotations — full annotation on UniProt →

Function. Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules. Activates AURKA by promoting its autophosphorylation at ‘Thr-288’ and protects this residue against dephosphorylation. TPX2 is inactivated upon binding to importin-alpha. At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activate AURKA kinase and stimulate local microtubule nucleation.

Subunit / interactions. Interacts with AURKA. Interacts with importin-alpha; leading to inactivate TPX2. Interacts with HNRNPU; this interaction recruits HNRNPU to spindle microtubules (MTs). Interacts with BCL2L10. Interacts with KIF11.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle. Spindle pole.

Tissue specificity. Expressed in lung carcinoma cell lines but not in normal lung tissues.

Similarity. Belongs to the TPX2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULW0-1	1	yes
Q9ULW0-2	2, HCA90

RefSeq proteins (1): NP_036244* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009675	TPX2_fam	Family
IPR015128	Aurora-A-bd	Domain
IPR027329	TPX2_C	Domain
IPR027330	TPX2_central_dom	Domain

Pfam: PF06886, PF09041, PF12214

UniProt features (35 total): modified residue 18, cross-link 4, helix 4, region of interest 2, sequence conflict 2, chain 1, splice variant 1, sequence variant 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

14 structures by resolution:

PDB	Title	Method	Resolution (Å)
6VPM	TPX2 residues 7-20 fused to Aurora A residues 116-389 with C290 disulfide bonded to …	X-RAY DIFFRACTION	1.58
6VPL	TPX2 residues 7-20 fused to Aurora A residues 116-389 with C290 disulfide bonded to …	X-RAY DIFFRACTION	1.86
6VPI	TPX2 residues 7-20 fused to Aurora A residues 116-389 C247V + D256N + C319V triple mutant …	X-RAY DIFFRACTION	2
5LXM	Crystal structure of Aurora-A bound to a hydrocarbon-stapled proteomimetic of TPX2	X-RAY DIFFRACTION	2.08
6VPJ	TPX2 residues 7-20 fused to Aurora A residues 116-389 C247V + C319V double mutant …	X-RAY DIFFRACTION	2.1
6VPH	TPX2 residues 7-20 fused to Aurora A residues 116-389 modified with cacodylate and in …	X-RAY DIFFRACTION	2.14
9SUY	TPX2 7-20 fused to Aurora-A residues 116-389, covalently modified on Cys290 by F104 …	X-RAY DIFFRACTION	2.27
3E5A	Crystal structure of Aurora A in complex with VX-680 and TPX2	X-RAY DIFFRACTION	2.3
3HA6	Crystal structure of aurora A in complex with TPX2 and compound 10	X-RAY DIFFRACTION	2.36
1OL5	Structure of Aurora-A 122-403, phosphorylated on Thr287, Thr288 and bound to TPX2 1-43	X-RAY DIFFRACTION	2.5
6VPG	TPX2 residues 7-20 fused to Aurora A residues 116-389 in complex with AMP-PNP	X-RAY DIFFRACTION	2.64
6XKA	TPX2 residues 7-20 fused to Aurora A residues 116-389 dephosphorylated, and CoAlated on …	X-RAY DIFFRACTION	2.65
4C3P	Structure of dephosphorylated Aurora A (122-403) bound to TPX2 and AMPPCP	X-RAY DIFFRACTION	2.69
6BJC	TPX2_mini decorated GMPCPP-microtubule	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULW0-F1	64.23	0.05

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, Mutated cancer genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytokinetic bridge; mitotic spindle

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

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

Post-translational modifications (22)

Type	Positions
Phosphoserine	257, 292, 293, 310, 359, 486, 738, 121, 125
N6-acetyllysine	305, 375, 128
Phosphothreonine	338, 369, 499, 59, 72, 147
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	477, 500, 641, 740

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-8854518	AURKA Activation by TPX2	curated
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	curated
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-69275	G2/M Transition	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-453274	Mitotic G2-G2/M phases	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5633007	Regulation of TP53 Activity	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 433 (showing top): GNF2_CKS1B, GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, MORF_BUB1, GOBP_REGULATION_OF_PHOSPHORYLATION, BASSO_B_LYMPHOCYTE_NETWORK, CROONQUIST_NRAS_SIGNALING_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN

GO Biological Process (8): mitotic cell cycle (GO:0000278), apoptotic process (GO:0006915), microtubule nucleation (GO:0007020), negative regulation of microtubule depolymerization (GO:0007026), activation of protein kinase activity (GO:0032147), cell division (GO:0051301), regulation of mitotic spindle organization (GO:0060236), mitotic spindle assembly (GO:0090307)

GO Molecular Function (5): protein kinase binding (GO:0019901), protein serine/threonine kinase activator activity (GO:0043539), molecular adaptor activity (GO:0060090), importin-alpha family protein binding (GO:0061676), protein binding (GO:0005515)

GO Cellular Component (10): spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), axon hillock (GO:0043203), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Regulation of TP53 Activity	1
G2/M Transition	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Cell Cycle, Mitotic	1
Transcriptional Regulation by TP53	1
Mitotic G2-G2/M phases	1
Cell Cycle	1
Gene expression (Transcription)	1

GO top-level categories

35 GO namespaces:

Category	Terms
cellular anatomical structure	5
mitotic nuclear division	2
mitotic spindle organization	2
binding	2
spindle	2
microtubule cytoskeleton	2
cell cycle	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
microtubule cytoskeleton organization	1
microtubule polymerization	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
positive regulation of protein kinase activity	1
cellular process	1
regulation of spindle organization	1
mitotic sister chromatid segregation	1
spindle assembly	1
kinase binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
molecular_function	1
protein binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
axon	1
neuronal cell body	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
activation of protein kinase activity	BP	direct assay
microtubule nucleation	BP	direct assay
mitotic spindle assembly	BP	direct assay
negative regulation of microtubule depolymerization	BP	direct assay
intercellular bridge	CC	direct assay
microtubule cytoskeleton	CC	direct assay
mitotic spindle	CC	direct assay
nucleoplasm	CC	direct assay
spindle	CC	direct assay
importin-alpha family protein binding	MF	direct assay
molecular adaptor activity	MF	direct assay
protein kinase binding	MF	physical interaction
protein serine/threonine kinase activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,704 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPX2	AURKA	O14965	884
TPX2	SPON2	Q9BUD6	811
TPX2	DLGAP5	Q15398	706
TPX2	KIF11	P52732	659
TPX2	KIF2C	Q99661	654
TPX2	UBE2C	O00762	650
TPX2	TOP2A	P11388	650
TPX2	KIF4A	O95239	621
TPX2	NUSAP1	Q9BXS6	621
TPX2	KIF20A	O95235	620
TPX2	MELK	Q14680	614
TPX2	BARD1	Q99728	612
TPX2	AURKB	Q96GD4	606
TPX2	KIF15	Q9NS87	603
TPX2	CDC20	Q12834	594

IntAct

Human interaction partners of TPX2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
AURKA	direct interaction	0.890	5
GOLGA2	physical association	0.720	6
CALR	physical association	0.560	3
CDH1	physical association	0.560	3
CDK5R1	physical association	0.560	3
DLST	physical association	0.560	3
NEK7	physical association	0.560	3
BAG2	association	0.530	1
HMMR	physical association	0.500	2
CDK6	phosphorylation reaction	0.440	1
NCK1	physical association	0.400	4
GRB2	physical association	0.400	2
PIK3R1	physical association	0.400	2
CHUK	physical association	0.400	1
CRK	physical association	0.400	1
IKBKB	physical association	0.400	1
KPNA4	physical association	0.400	1
NAP1L1	physical association	0.370	1
THAP11	physical association	0.370	1
AFAP1	association	0.350	1
MAP1LC3B2	association	0.350	1
FBXW7	proximity	0.270	4
SMAD4	proximity	0.270	4
SMARCA4	proximity	0.270	4
AKT1	proximity	0.270	1
SPOP	proximity	0.270	1
TP53	proximity	0.270	1

BioGRID (396 interactions; top human partners by supporting records): AURKA (Affinity Capture-MS; 17 records), BRCA1 (Affinity Capture-MS; 5 records), LMNA (Proximity Label-MS; 4 records), GSTM3 (Affinity Capture-MS; 3 records), KIFC1 (Cross-Linking-MS (XL-MS); 3 records), MAPK14 (Affinity Capture-MS; 3 records), MYC (Affinity Capture-MS; 3 records), RPA1 (Proximity Label-MS; 3 records), ANLN (Affinity Capture-MS; 2 records), CDK12 (Affinity Capture-MS; 2 records), CIC (Affinity Capture-MS; 2 records), DCAF13 (Affinity Capture-MS; 2 records), ESR2 (Affinity Capture-MS; 2 records), FZR1 (Affinity Capture-Western; 2 records), HELLS (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 6 of 7 signaling interactions:

A	Effect	B	Mechanism
AURKA	“up-regulates activity”	TPX2	phosphorylation
TPX2	“up-regulates activity”	CLASP1	binding
CDK5	“up-regulates quantity by stabilization”	TPX2	phosphorylation
CDK1	“down-regulates activity”	TPX2	phosphorylation
TPX2	“down-regulates activity”	KIF11	binding
CDK2	“down-regulates activity”	TPX2	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Aurora A-TPX2-NuMA complex	3	AURKA, NUMA1, TPX2
Aurora A-TPX2 complex	2	AURKA, TPX2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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
Viral Infection Pathways	5	6.7×	7e-03
Infectious disease	6	6.5×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein stabilization	5	12.4×	4e-03

Disease & clinical

Genetic variants

Variant evidence for TPX2: 119 ClinVar records (0 pathogenic / likely pathogenic); 9 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	7
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,193):

Position(s)	Effect	Δscore	Sites
20:31757405–31757406	acceptor_loss	1.0000	6
20:31757583–31757584	donor_loss	1.0000	5
20:31760024	acceptor_gain	1.0000
20:31760054	acceptor_gain	1.0000
20:31760055–31760056	acceptor_loss	1.0000	6
20:31760180–31760181	donor_loss	1.0000	5
20:31766554–31766555	acceptor_loss	1.0000	4
20:31766683–31766684	donor_loss	1.0000	4
20:31771550	acceptor_gain	1.0000
20:31771558	acceptor_gain	1.0000

AlphaMissense

805 missense substitutions predicted likely pathogenic (of 4,908 scored), across 251 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F625	8	0.932	0.990
F457	8	0.923	0.996
F538	8	0.911	0.990
F307	8	0.904	0.988
F638	8	0.894	0.987
F489	8	0.893	0.979
F741	8	0.888	0.987
F540	8	0.882	0.981
F433	8	0.861	0.980
F334	7	0.946	0.988
F566	7	0.931	0.989
C462	7	0.908	0.990
F262	7	0.898	0.962
F593	7	0.875	0.974
F35	7	0.871	0.956
F745	7	0.859	0.970
F283	7	0.832	0.952
D32	7	0.682	0.758
P739	6	0.959	0.983
R341	6	0.903	0.977

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

10 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	4.73e-13
Liver Hepatocellular Carcinoma (validation)	unfavorable	2.38e-10
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	5.19e-09
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	4.2e-08
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.31e-07
Pancreatic Adenocarcinoma (TCGA)	unfavorable	1.36e-05
Kidney Chromophobe (TCGA)	unfavorable	1.64e-05
Lung Adenocarcinoma (TCGA)	unfavorable	1.66e-05
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000735
Lung Adenocarcinoma (validation)	unfavorable	0.000822

Disease associations

OMIM: gene MIM:605917 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

GWAS associations

9 associations:

Study	Trait	p-value
GCST90002396_452	Mean reticulocyte volume	9e-37
GCST009067_1	Mosaic loss of chromosome Y (Y chromosome dosage)	2e-17
GCST009375_7	Mosaic loss of chromosome Y (Y chromosome dosage)	2e-17
GCST010703_197	Brain morphology (MOSTest)	1e-14
GCST90002387_323	Immature fraction of reticulocytes	2e-12
GCST90002394_564	Monocyte percentage of white cells	5e-12
GCST004639_8	Prudent dietary pattern	2e-6
GCST003030_10	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	3e-6
GCST003030_9	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	4e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0007679	oppositional defiant disorder measurement
EFO:0008111	diet measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004346	neuroimaging measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3883304 (PROTEIN COMPLEX), CHEMBL5389 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 771 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1090479	GSK-1070916	1	187
CHEMBL3544932	TAK-901	1	584

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

32 measured of 32 human assays (33 total across all organisms); most potent 32 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Alisertib	IC50	0.04 nM
2-[(1E,3E)-5-[(2E)-3-(3-{[(5R)-5-carbamoyl-5-{[4- (3-chloro-2-fluorophenoxy)-1-{[6-(1,3-thiazol-2- ylamino)pyridin-2- yl]methyl}cyclohexyl]formamido}pentyl]carbamoyl}propyl)-1- ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3- dien-1-yl]-1-ethyl-3,3-dimethylindol-1-ium-5- sulfonate (Compound III)	KD	0.2 nM
2-[(1E,3E)-5-[(2E)-3-(3-{[(5R)-5-carbamoyl-5-[(4- {[13-chloro-10-(2-fluoro-6-methoxyphenyl)-3,5,9- triazatricyclo[9.4.0.0,⁷]pentadeca- 1(11),2(7),3,5,9,12,14-heptaen-4-yl]amino}-2- methoxyphenyl)formamido]pentyl]carbamoyl}propyl)-1- ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3- dien-1-yl]-1-ethyl-3,3-dimethylindol-1-ium-5- sulfonate (Compound I)	KD	0.273 nM
VX-689	IC50	0.6 nM
Compound II: Ac-D-Arg6-D-Lys(PromoFluor 647)-D-Lys(MLN8237*)-NH2	KD	5.2 nM
CHEMBL5598235	KD	18 nM
CHEMBL5596260	KD	50 nM
GSK-1070916	IC50	59 nM
CHEMBL5598288	KD	79 nM
CHEMBL5596916	KD	100 nM
CHEMBL5598166	KD	158 nM
CHEMBL5597558	KD	1260 nM
6-(2-chlorobenzyl)-2-(4-ethylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	1500 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
2-(4-ethylpiperazin-1-yl)-6-(2,3,4-trimethoxybenzyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	1700 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
3-Hydroxybenzoate, II	KI	2370 nM
2-(4-ethylpiperazin-1-yl)-6-(2,4,5-trimethoxybenzyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	2400 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
2-(4-ethylpiperazin-1-yl)-6-(3,4,5-trimethoxybenzyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	2500 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-(3,4-diethoxybenzyl)-2-(4-ethylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	2800 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-(4-ethoxy-3-methoxybenzyl)-2-(4-ethylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	3500 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
CHEMBL5597404	EC50	3900 nM
CHEMBL5597168	EC50	5500 nM
4-allyl-2-methyl-N-(pyridin-2-ylmethyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide	IC50	5600 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-(4-bromobenzyl)-2-(4-propylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	13600 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	IC50	17200 nM
CHEMBL5596300	EC50	20000 nM
6-(3-bromobenzyl)-2-(4-propylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	21000 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-((5-bromothiophen-2-yl)methyl)-2-(4-propylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	23000 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-(2,3-difluorobenzyl)-2-(4-propylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	27800 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-(4-ethylbenzyl)-2-(4-propylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	32200 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-(3,4-diethoxybenzyl)-2-(4-propylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	42200 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
6-(4-ethoxy-3-methoxybenzyl)-2-(4-propylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine	IC50	44800 nM	US-20240342179: TREATMENT OF CANCERS OR NEOPLASMS BY INHIBITING KIF15
CHEMBL5597299	KD	145000 nM

ChEMBL bioactivities

40 potent at pChembl≥5 of 43 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.21	IC50	6.2	nM	CHEMBL587029
8.10	IC50	7.9	nM	CHEMBL1090832
7.80	IC50	16	nM	CHEMBL1243200
7.75	Kd	18	nM	CHEMBL5598235
7.72	Kd	19	nM	CHEMBL5597404
7.68	IC50	21	nM	TAK-901
7.39	IC50	41	nM	CHEMBL1243326
7.21	IC50	62	nM	CHEMBL1243137
7.20	Kd	63	nM	CHEMBL5596916
7.12	IC50	76	nM	CHEMBL1090508
7.10	Kd	79	nM	CHEMBL5596260
7.00	Kd	100	nM	CHEMBL5598288
6.89	IC50	128	nM	CHEMBL1090670
6.83	IC50	149	nM	CHEMBL1243294
6.80	Kd	158	nM	CHEMBL5598166
6.70	Kd	200	nM	CHEMBL5597168
6.31	Ki	490	nM	GSK-1070916
6.31	Ki	492	nM	GSK-1070916
6.23	IC50	584	nM	CHEMBL1089985
6.23	IC50	586	nM	CHEMBL1242977
6.02	Kd	955	nM	CHEMBL5596300
6.02	IC50	964	nM	CHEMBL1243073
6.01	IC50	982	nM	CHEMBL1089986
5.96	IC50	1100	nM	GSK-1070916
5.90	Kd	1260	nM	CHEMBL5597558
5.89	EC50	1300	nM	CHEMBL5596916
5.81	IC50	1546	nM	CHEMBL1243008
5.81	IC50	1544	nM	CHEMBL1243042
5.66	EC50	2200	nM	CHEMBL5598288
5.63	IC50	2342	nM	CHEMBL1243009
5.46	EC50	3500	nM	CHEMBL5596260
5.41	EC50	3900	nM	CHEMBL5597404
5.35	EC50	4500	nM	CHEMBL5596916
5.26	EC50	5500	nM	CHEMBL5597168
5.23	EC50	5900	nM	CHEMBL5596260
5.21	EC50	6100	nM	CHEMBL5597404
5.19	EC50	6400	nM	CHEMBL5597168
5.16	EC50	6900	nM	CHEMBL5598288

PubChem BioAssay actives

45 with measured affinity, of 72 total; 31 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
2-[(1E,3E,5E)-5-[3-[4-[[(5R)-6-amino-5-[[4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoyl]amino]-6-oxohexyl]amino]-4-oxobutyl]-1-ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3-dienyl]-1-ethyl-3,3-dimethylindol-1-ium-5-sulfonate	1800235: Dissociation Kinetics Assay from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	kd	0.0005	uM
2-[(1E,3E,5E)-5-[3-[4-[[(5R)-6-amino-5-[[4-(3-chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)-2-pyridinyl]methyl]cyclohexanecarbonyl]amino]-6-oxohexyl]amino]-4-oxobutyl]-1-ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3-dienyl]-1-ethyl-3,3-dimethylindol-1-ium-5-sulfonate	1800235: Dissociation Kinetics Assay from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	kd	0.0005	uM
4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid	1800233: Inhibition Assay Protocol A from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	ki	0.0019	uM
4-(3-chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)-2-pyridinyl]methyl]cyclohexane-1-carboxylic acid	1800233: Inhibition Assay Protocol A from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	ki	0.0022	uM
(2E)-3-[4-[[5-[[2-[[2-[[2-[[2-[[2-[[2-acetamido-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-(diaminomethylideneazaniumyl)pentanoyl]amino]-6-[[1-amino-6-[[4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]amino]-4-oxobutyl]-1-ethyl-2-[(2E,4E)-5-(1-ethyl-3,3-dimethyl-5-sulfonatoindol-1-ium-2-yl)penta-2,4-dienylidene]-3-methylindole-5-sulfonate	1800235: Dissociation Kinetics Assay from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	kd	0.0043	uM
1-[3-[5-chloro-4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]-N,N-dimethylmethanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0062	uM
1-[4-[5-chloro-4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]-N,N-dimethylmethanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0079	uM
2-anilino-N-[4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.0160	uM
4-(4-chloro-3-pyridin-2-yloxyphenyl)-N-cyclopropylsulfonyl-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0180	uM
4-(4-chloro-3-pyridin-2-yloxyphenyl)-N-(dimethylsulfamoyl)-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0190	uM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1419650: Inhibition of Aurora A/TPX2 (unknown origin) pre-incubated for 1 hr followed by FL-Kemptide substrate and ATP addition	ic50	0.0210	uM
4-(4-fluorophenyl)-N-[4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]phthalazin-1-amine	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.0410	uM
2-anilino-N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.0620	uM
4-(4-chloro-3-pyrazin-2-yloxyphenyl)-N-(dimethylsulfamoyl)-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0630	uM
N,N-dimethyl-1-[4-[4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]methanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0760	uM
4-(4-chlorophenyl)-N-cyclopropylsulfonyl-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0790	uM
4-(4-chlorophenyl)-N-(dimethylsulfamoyl)-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.1000	uM
N,N-dimethyl-1-[3-[4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]methanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.1280	uM
N-[4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-4-phenylphthalazin-1-amine	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.1490	uM
4-(4-chlorophenyl)-7-methyl-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.1580	uM
4-(4-chloro-3-cyanophenyl)-7-methyl-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.2000	uM
3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethylpyrazol-3-yl]phenyl]-1,1-dimethylurea	1419700: Inhibition of human Aurora A/TPX2 (unknown origin) pre-incubated for 30 mins before Biotin-Ahx-RARRRLSFFFFAKKK-NH2 substrate addition and measured after 120 mins	ki	0.4900	uM
4-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.5840	uM
N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-3-(trifluoromethyl)benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.5860	uM
4-(4-chloro-3-cyanophenyl)-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.9550	uM
N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-3-phenoxybenzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.9640	uM
4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.9820	uM
4-(4-chlorophenyl)-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	1.2600	uM
N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-2-phenoxybenzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	1.5440	uM
3-chloro-N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	1.5460	uM
4-chloro-N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	2.3420	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, affects expression, affects localization	4
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
cobaltous chloride	decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Cadmium	decreases expression, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
SP2509	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	decreases expression	1
nivalenol	increases expression	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1105942	Binding	Inhibition of Aurora A/TPX2 at 5 uM	Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. — *Bioorg Med Chem Lett*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 185 trials:

NCT	Phase	Status	Title
NCT00152750	Phase 4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	Phase 4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	Phase 4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	Phase 4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	Phase 4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	Phase 4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	Phase 4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	Phase 3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	Phase 3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	Phase 3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	Phase 3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	Phase 3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	Phase 3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	Phase 3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	Phase 3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	Phase 3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	Phase 3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	Phase 2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	Phase 2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	Phase 2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	Phase 2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	Phase 2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	Phase 2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	Phase 2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	Phase 2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	Phase 2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	Phase 2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	Phase 2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	Phase 2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	Phase 2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	Phase 2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	Phase 2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	Phase 2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	Phase 2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	Phase 2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	Phase 2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	Phase 2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	Phase 2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	Phase 2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03530293	Phase 2	TERMINATED	Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome
NCT03625453	Phase 2	COMPLETED	Study of ABX-1431 in Adult Patients With Tourette Syndrome or Chronic Motor Tic Disorder
NCT03651726	Phase 2	UNKNOWN	A Study to Examine the Efficacy of a Therapeutic THX-110 for Tourette Syndrome
NCT03732534	Phase 2	TERMINATED	Rollover Study for Continuing NBI-98854 Administration in Pediatric Subjects With Tourette Syndrome
NCT03944447	Phase 2	UNKNOWN	Outcomes Mandate National Integration With Cannabis as Medicine
NCT04007991	Phase 2	COMPLETED	Ecopipam Tablets to Study Tourette’s Syndrome in Children and Adolescents
NCT04354103	Phase 2	TERMINATED	Atomoxetine in Patients With Tourette’s Syndrome
NCT04978428	Phase 2	COMPLETED	Epidiolex in Obsessive Compulsive Disorder and Related Disorders
NCT05126888	Phase 2	NOT_YET_RECRUITING	SCI-110 in the Treatment of Tourette Syndrome
NCT05434546	Phase 2	COMPLETED	A Study to Explore the Effect of Sepranolone in Tourette Syndrome
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06194305	Phase 2	RECRUITING	Multimodal Profiling of Response to Pediatric Comprehensive Behavioral Intervention for Tics
NCT06315751	Phase 2	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Gemlapodect (NOE-105) in Adults and Adolescents With Tourette Syndrome
NCT06678737	Phase 2	RECRUITING	CBIT+TMS R33 Phase
NCT00139308	Phase 1	COMPLETED	High Frequency Stimulation of the GPi or Thalamus in Tourette’s Syndrome
NCT00634556	Phase 1	COMPLETED	Dopaminergic Effects on Cortical Function in Tourette’s (Levodopa Protocol)
NCT00952601	Phase 1	TERMINATED	Pilot Study of the Modified Atkins Diet for Tourette Syndrome
NCT01440023	Phase 1	COMPLETED	Developing Cognitive Training for Tourette Syndrome
NCT01719523	Phase 1	COMPLETED	Open-Trial of EPI-743 for Adults With Tourette Syndrome
NCT02134080	Phase 1	TERMINATED	FAAH Inhibitor Trial for Adults With Tourette Syndrome

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TPX2 across ~30M SureChEMBL compounds — explore on Sugi Predict.