AURKC

Summary

AURKC (aurora kinase C, HGNC:11391) is a protein-coding gene on chromosome 19q13.43, encoding Aurora kinase C (Q9UQB9). Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis.

This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6795 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 5 (Definitive, ClinGen)
• Clinical variants (ClinVar): 93 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 41 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001015878

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11391
Approved symbol	AURKC
Name	aurora kinase C
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	AurC, ARK3
Ensembl gene	ENSG00000105146
Ensembl biotype	protein_coding
OMIM	603495
Entrez	6795

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 nonsense_mediated_decay

ENST00000302804, ENST00000415300, ENST00000594599, ENST00000596375, ENST00000598785, ENST00000599062, ENST00000601799, ENST00000923144

RefSeq mRNA: 3 — MANE Select: NM_001015878 NM_001015878, NM_001015879, NM_003160

CCDS: CCDS33128, CCDS46205, CCDS46206

Canonical transcript exons

ENST00000302804 — 7 exons

Exon	Start	End
ENSE00000729002	57232542	57232680
ENSE00001469889	57231023	57231306
ENSE00003475790	57233460	57233608
ENSE00003522383	57235247	57235548
ENSE00003571111	57231742	57231787
ENSE00003670348	57234884	57235058
ENSE00003682833	57232033	57232224

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 98.42.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8924 / max 165.5482, expressed in 225 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177745	0.4491	139
177743	0.2283	72
177744	0.2026	60
177742	0.0125	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.42	gold quality
secondary oocyte	CL:0000655	98.19	gold quality
left testis	UBERON:0004533	95.01	gold quality
right testis	UBERON:0004534	94.73	gold quality
testis	UBERON:0000473	92.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.48	gold quality
adult organism	UBERON:0007023	86.66	gold quality
sperm	CL:0000019	86.43	gold quality
male germ cell	CL:0000015	84.51	gold quality
endometrium epithelium	UBERON:0004811	78.59	gold quality
stromal cell of endometrium	CL:0002255	77.45	gold quality
spleen	UBERON:0002106	76.80	gold quality
apex of heart	UBERON:0002098	76.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.27	gold quality
cerebellar hemisphere	UBERON:0002245	75.43	gold quality
cerebellar cortex	UBERON:0002129	75.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.60	gold quality
right lobe of liver	UBERON:0001114	74.51	gold quality
gastrocnemius	UBERON:0001388	74.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.77	gold quality
muscle of leg	UBERON:0001383	73.71	gold quality
cerebellum	UBERON:0002037	73.05	gold quality
spinal cord	UBERON:0002240	72.98	gold quality
lower esophagus mucosa	UBERON:0035834	72.96	gold quality
adenohypophysis	UBERON:0002196	72.28	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.42	gold quality
lower esophagus	UBERON:0013473	71.39	gold quality
skin of abdomen	UBERON:0001416	71.18	gold quality
mucosa of stomach	UBERON:0001199	71.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZBTB32

miRNA regulators (miRDB)

8 targeting AURKC, 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-8485	100.00	77.57	4731
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 40)

• association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C (PMID:15316025)
• Aurora-C interacts with the inner centromere protein (INCENP) at the carboxyl terminal end spanning the conserved IN box domain. (PMID:15499654)
• Therefore, we speculated that Aurora C-SV might also contribute to the regulation of chromosome segregation and cytokinesis. (PMID:15670791)
• Aurora-C is a chromosomal passenger protein that disrupts the association of INCENP with Aurora-B and may serve as a key regulator in cell division (PMID:15917996)
• Aurora-c is directly associated with surwvivin and is required for cytokinesis. (PMID:15938719)
• A role of Aurora-C in the development and progression of cancer especially in the presence of mutated p53. (PMID:16258285)
• Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. (PMID:17435757)
• Results demonstrate that human Auroras a regulator of cell morphology and cell growth, and that the non-conserved T191 in the activation loop of Auroras of major importance for its regulation. (PMID:17637569)
• Aurora C phosphorylates TRF2 (PMID:18309533)
• A functional AURKC protein is necessary for male meiotic cytokinesis while its absence does not impair oogenesis. (PMID:19147683)
• Data show that SNS-314 is a novel, potent, and selective inhibitor of Aurora kinases A, B, and C. (PMID:19649632)
• Aurora-C can perform the same essential functions as Aurora-B in mitosis: regulation of kinetochore-microtubule attachments, the spindle assembly checkpoint, and cytokinesis (PMID:19713763)
• Aurora-C mRNA was reduced to 0.20 +/- 0.32 fold (P < 0.01) in 13 seminomas and up-regulated in one case (PMID:20629650)
• We confirm in this study the research interest of the recurrent mutation c.144delC in the gene AURKC in male infertility with high rates of large-headed spermatozoa (PMID:21353399)
• Aurora C mRNA is up-regulated with Aurora B after activation of the embryonic genome and both proteins were detected in early Day 4 embryos. (PMID:21493633)
• the study demonstrated that TACC1 localizes at the midbody during cytokinesis and interacts with and is a substrate of Aurora-C, which warrant further investigation in order to elucidate the functional significance of this interaction. (PMID:21531210)
• we show that elevated AURKC increases the proliferation, transformation and migration of cancer cells (PMID:21710690)
• Molecular analysis of the AURKC gene was carried out in two brothers presenting with a typical large-headed spermatozoa phenotype. Both affected brothers were heterozygous for the c.144delC mutation in the AURKC gene. (PMID:21733974)
• Overexpressed Aurora-C (AURKC) is an oncogene. Overexpression of Aurora-C induces abnormal cell division resulting in centrosome amplification and multinucleation. Cells overexpressing active Aurora-C induced tumour formation in nude mice. (PMID:22046298)
• Investigators identified a new non-sense mutation in aurora kinase C, p.Y248*, in 10 unrelated individuals of European and North African origin; this mutation is associated with macrozoospermia and male infertility. (PMID:22888167)
• The immunoreactivity profile of AURKA, AURKB and AURKC in this study showed a significantly reduced expression in PCa cases compared to BPH cases. (PMID:23075505)
• expression of AURKC, OIP5, PIWIL2 and TAF7L differed between patients with Acute myeloid leukemia, myelodysplastic syndrome and healthy controls in a gender-dependent manner (PMID:23292864)
• Here we provide evidence for the first time of Aurora-C overexpression and gene amplification. (PMID:23581231)
• Our data indicate that the AURKC c.144delC mutation has a relatively high carrier frequency in the Moroccan population. (PMID:24484996)
• Aberrantly expressed Aurora-C in somatic cancer cells may impair spindle checkpoint assembly by displacing the centromeric localization of chromosomal passenger complexes. (PMID:24603334)
• This review will describe the functions of each Aurora kinase which include Aurora A (AURKA), Aurora B (AURKB) and Aurora C (AURKC summarize their involvement in leukemia and discuss inhibitor development and efficacy in leukemia clinical trials (PMID:24632603)
• AURKC mutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. (PMID:25219909)
• Data indicate that the selective Aurora A, B, and C inhibitor SAR156497 showed antineoplastic activity in HCT116 cell xenograft model. (PMID:25369539)
• Low AURKC expression is associated with cancer. (PMID:25990457)
• Overexpression of AURKC is associated with breast tumors. (PMID:25994570)
• may play an important role in the development of colorectal cancer (PMID:26118178)
• Homozygous c.144delC mutation in AURKC gene in infertile men with macrozoospermia in the Tunisian population (PMID:26341096)
• Aurora-C interactions with members of the Chromosome Passenger Complex (CPC), Survivin and Inner Centromere Protein (INCENP) in reference to known Aurora-B interactions to understand the functional significance of Aurora-C overexpression in human cancer cells, is reported. (PMID:27332895)
• Patients presenting with a monomorphic teratozoospermia such as globozoospermia or macrospermia with more than 85% of the spermatozoa presenting this specific abnormality have been analyzed permitting to identify several key genes for spermatogenesis such as AURKC and DPY19L2. (PMID:27779748)
• Identification and characterization of AURKB and AURKC variants associated with maternal aneuploidy has been reported. (PMID:28369513)
• Two novel DMRs, located in RPS6KA4/MIR1237 and the AURKC promoter, were found to be hypermethylated in WT (PMID:28930610)
• The data suggest that AKA is the vertebrate ancestral gene, and that AKB and AKC resulted from gene duplication in placental mammals. (PMID:29283376)
• Teratozoospermia is not correlated with c.144delC mutation in the AURKC gene in the men of the Sichuan area. Therefore, large-scale genotyping of the AURKC gene may not be necessary clinically among Chinese patients with idiopathic teratozoospermia. (PMID:29738175)
• The epigenetic targets AURKB, AURKC and DNMT3B, and the global DNA methylation profile are regulated during HIV-1 replication in CD4+ T cells, and this regulation can be influenced by the activation state of the cell at the time of infection. (PMID:30077875)
• This study showed the role of Lactobacilli in down-regulation of TSGA10, AURKC, OIP5 and AKAP4 genes. Such expression change might be involved in the anticancer effects of these Lactobacilli. The underlying mechanisms of these observations are not clear but epigenetic modulatory mechanisms may participate in this process. (PMID:30545223)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Aurkc	ENSMUSG00000070837
rattus_norvegicus	Aurkc	ENSRNOG00000015825

Paralogs (2): AURKA (ENSG00000087586), AURKB (ENSG00000178999)

Protein

Protein identifiers

Aurora kinase C — Q9UQB9 (reviewed: Q9UQB9)

Alternative names: Aurora 3, Aurora/IPL1-related kinase 3, Aurora/IPL1/Eg2 protein 2, Serine/threonine-protein kinase 13, Serine/threonine-protein kinase aurora-C

All UniProt accessions (5): B4DXA6, Q9UQB9, M0QX60, M0QYK8, Q5Y191

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Also plays a role in meiosis and more particularly in spermatogenesis. Has redundant cellular functions with AURKB and can rescue an AURKB knockdown. Like AURKB, AURKC phosphorylates histone H3 at ‘Ser-10’ and ‘Ser-28’. AURKC phosphorylates the CPC complex subunits BIRC5/survivin and INCENP leading to increased AURKC activity. Phosphorylates TACC1, another protein involved in cell division, at ‘Ser-228’.

Subunit / interactions. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; predominantly independent AURKB- and AURKC-containing complexes exist; in the complex interacts directly with BIRC5/survivin and INCENP. Interacts with TACC1.

Subcellular location. Nucleus. Chromosome. Centromere. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Isoform 1 and isoform 2 are expressed in testis. Elevated expression levels were seen only in a subset of cancer cell lines such as Hep-G2, Huh-7 and HeLa. Expression is maximum at M phase.

Disease relevance. Spermatogenic failure 5 (SPGF5) [MIM:243060] An infertility disorder caused by spermatogenesis defects. Semen from affected men show close to 100% morphologically abnormal multiflagellar spermatozoa with low motility, oversized irregular heads, and abnormal midpiece and acrosome. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Okadaic acid, an inhibitor of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein phosphatase 5 (PP5), increases AURKC activity. AURKC is also stabilized through its interaction with INCENP, which also acts as an activator.

Induction. Expression is cell cycle-regulated, with an increase during G2 and M phases.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UQB9-1	1	yes
Q9UQB9-2	2
Q9UQB9-3	3, Aurora C-SV

RefSeq proteins (3): NP_001015878, NP_001015879, NP_003151 (=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
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR030616	Aur-like	Family

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• 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 (42 total): helix 14, strand 7, sequence variant 3, mutagenesis site 3, sequence conflict 3, splice variant 2, region of interest 2, binding site 2, chain 1, domain 1, turn 1, compositionally biased region 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6GR8	X-RAY DIFFRACTION	1.75
6GR9	X-RAY DIFFRACTION	2.25
9ESA	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQB9-F1	85.25	0.71

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): 166 (proton acceptor)

Ligand- & substrate-binding residues (2): 49–57; 72

Post-translational modifications (1): 198

Mutagenesis-validated functional residues (3):

Position	Phenotype
72	impairs kinase activity.
166	impairs kinase activity, and keeps aurkc with the chromosomes until the end of mitosis.
198	impairs kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_CHROMOSOME_LOCALIZATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, MARTINEZ_RB1_TARGETS_UP, GOBP_MITOTIC_SPINDLE_ASSEMBLY, GOBP_ORGANELLE_FISSION, GOBP_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIVISION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, ABE_VEGFA_TARGETS_2HR, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CYTOKINESIS

GO Biological Process (8): protein phosphorylation (GO:0006468), mitotic spindle organization (GO:0007052), attachment of spindle microtubules to kinetochore (GO:0008608), regulation of cytokinesis (GO:0032465), positive regulation of cytokinesis (GO:0032467), mitotic spindle midzone assembly (GO:0051256), cell division (GO:0051301), meiotic cell cycle (GO:0051321)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (14): kinetochore (GO:0000776), condensed chromosome (GO:0000793), spindle pole (GO:0000922), nucleus (GO:0005634), centrosome (GO:0005813), spindle (GO:0005819), spindle microtubule (GO:0005876), midbody (GO:0030496), chromosome passenger complex (GO:0032133), spindle midzone (GO:0051233), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
cellular anatomical structure	4
protein kinase activity	3
spindle	3
cytokinesis	2
phosphorylation	1
protein modification process	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
microtubule binding	1
cell cycle process	1
metaphase chromosome alignment	1
regulation of cell cycle process	1
regulation of cell division	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
mitotic spindle elongation	1
spindle midzone assembly	1
mitotic spindle assembly	1
mitotic nuclear division	1
mitotic cell cycle process	1
cellular process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
condensed chromosome, centromeric region	1
supramolecular complex	1

Protein interactions and networks

STRING

2206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AURKC	INCENP	Q9NQS7	978
AURKC	CDCA8	Q53HL2	871
AURKC	H3-4	Q16695	800
AURKC	H3-7	Q5TEC6	800
AURKC	H3-5	Q6NXT2	800
AURKC	H3C14	Q71DI3	800
AURKC	H3-3A	P06351	799
AURKC	H3C1	P02295	799
AURKC	CPEB1	Q9BZB8	782
AURKC	BIRC5	O15392	757
AURKC	DPY19L2	Q6NUT2	682
AURKC	SPATA16	Q9BXB7	673
AURKC	BUB1B	O60566	635
AURKC	CENPA	P49450	614
AURKC	AURKB	Q96GD4	593

IntAct

44 interactions, top by confidence:

A	B	Type	Score
AURKB	INCENP	psi-mi:“MI:0914”(association)	0.960
AURKB	BIRC5	psi-mi:“MI:0914”(association)	0.950
AURKC	INCENP	psi-mi:“MI:0403”(colocalization)	0.810
AURKC	INCENP	psi-mi:“MI:0915”(physical association)	0.810
AURKC	INCENP	psi-mi:“MI:0217”(phosphorylation reaction)	0.810
INCENP	AURKC	psi-mi:“MI:0915”(physical association)	0.810
AURKC	BIRC5	psi-mi:“MI:0915”(physical association)	0.740
AURKC	BIRC5	psi-mi:“MI:0403”(colocalization)	0.740
AURKC	BIRC5	psi-mi:“MI:0914”(association)	0.740
BIRC5	AURKC	psi-mi:“MI:0915”(physical association)	0.740
OTX2	AURKC	psi-mi:“MI:0915”(physical association)	0.600
CADPS	AURKC	psi-mi:“MI:0915”(physical association)	0.560
BIRC7	AURKC	psi-mi:“MI:0915”(physical association)	0.560
SRPK1	AURKC	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (72): HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), CDC37 (Affinity Capture-MS), MYH1 (Affinity Capture-MS), MYH8 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), USP19 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), INCENP (Affinity Capture-MS), C12orf43 (Affinity Capture-MS), DHX38 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3S724, A4IGM9, D7UQM5, E2RTQ7, O01427, O08875, O14408, O55099, O59790, O70126, P00518, P10665, P18652, P18653, P18654, P31325, P51812, P59241, P97477, Q00771, Q15349, Q16816, Q18846, Q21734, Q4KTY1, Q501V0, Q58D94, Q61XD3, Q63531, Q66JF3, Q6C3J2, Q6CWQ4, Q6DE08, Q6FV07, Q6GPL3, Q6NW76, Q755C4, Q7TPS0, Q7YRC6, Q91819

Diamond homologs: A0A8I3S724, A2VDZ4, A2XFF4, A4IGM9, A5GFW1, A7SNN5, B0WAU8, B2GUY1, B3DL84, B3M6I4, B3NE99, B4HBU3, B4IAQ8, B4J3F1, B4KYX8, B4LDJ6, B4MXR8, B4PDM5, B4QK53, B8BBT7, D7UQM5, E2RTQ7, O00444, O01427, O14965, O55099, O59790, O64629, O70126, O88445, O97143, P05986, P06244, P0C8M8, P38991, P59241, P92937, P97477, Q0JI49, Q10LQ2

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
AURKC	“up-regulates activity”	H3C1	phosphorylation
“AMG 900”	down-regulates	AURKC	“chemical inhibition”
CCT129202	down-regulates	AURKC	“chemical inhibition”
CCT137690	down-regulates	AURKC	“chemical inhibition”
N-[5-[(2R)-2-methoxy-1-oxo-2-phenylethyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methyl-1-piperazinyl)benzamide	down-regulates	AURKC	“chemical inhibition”
3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethyl-3-pyrazolyl]phenyl]-1,1-dimethylurea	down-regulates	AURKC	“chemical inhibition”
PHA-680632	down-regulates	AURKC	“chemical inhibition”
“SNS-314 Mesylate”	down-regulates	AURKC	“chemical inhibition”
N-[4-[[4-(4-methyl-1-piperazinyl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]thio]phenyl]cyclopropanecarboxamide	down-regulates	AURKC	“chemical inhibition”
ZM447439	down-regulates	AURKC	“chemical inhibition”
3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethyl-3-pyrazolyl]phenyl]-1,1-dimethylurea	“down-regulates activity”	AURKC	“chemical inhibition”
AURKC	up-regulates	“Histone H3”	phosphorylation
AURKC	“up-regulates activity”	NFKBIA	phosphorylation
N-[4-[[4-(4-methyl-1-piperazinyl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]thio]phenyl]cyclopropanecarboxamide	“down-regulates activity”	AURKC	“chemical inhibition”
AURKC	“up-regulates activity”	TACC1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	56
Likely benign	2
Benign	20

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1028940	NM_001015878.2(AURKC):c.744C>G (p.Tyr248Ter)	Pathogenic
6307	NM_001015878.2(AURKC):c.686G>A (p.Cys229Tyr)	Pathogenic
66088	NM_001015878.2(AURKC):c.436-2A>G	Pathogenic
1335371	NM_001015878.2(AURKC):c.54dup (p.Glu19fs)	Likely pathogenic
4537477	NM_001015878.2(AURKC):c.550del (p.Asp184fs)	Likely pathogenic

SpliceAI

1074 predictions. Top by Δscore:

Variant	Effect	Δscore
19:57231218:G:GT	donor_gain	1.0000
19:57231219:A:T	donor_gain	1.0000
19:57231303:GAGT:G	donor_gain	1.0000
19:57231305:GT:G	donor_gain	1.0000
19:57231330:G:GT	donor_gain	1.0000
19:57231338:G:GT	donor_gain	1.0000
19:57232027:T:TA	acceptor_gain	1.0000
19:57232030:CAG:C	acceptor_loss	1.0000
19:57232031:A:AG	acceptor_gain	1.0000
19:57232031:AGGC:A	acceptor_gain	1.0000
19:57232032:G:GA	acceptor_gain	1.0000
19:57232032:GGC:G	acceptor_gain	1.0000
19:57232032:GGCG:G	acceptor_gain	1.0000
19:57232172:G:GT	donor_gain	1.0000
19:57232220:CTACA:C	donor_gain	1.0000
19:57232221:TACA:T	donor_gain	1.0000
19:57232222:ACA:A	donor_gain	1.0000
19:57232223:CA:C	donor_gain	1.0000
19:57232223:CAGT:C	donor_loss	1.0000
19:57232224:AGT:A	donor_loss	1.0000
19:57232225:G:A	donor_loss	1.0000
19:57232225:G:GG	donor_gain	1.0000
19:57232226:T:A	donor_loss	1.0000
19:57232230:G:GT	donor_gain	1.0000
19:57232231:A:T	donor_gain	1.0000
19:57234871:T:A	acceptor_gain	1.0000
19:57234882:A:AG	acceptor_gain	1.0000
19:57234882:AG:A	acceptor_gain	1.0000
19:57234882:AGGAG:A	acceptor_gain	1.0000
19:57234883:G:GT	acceptor_gain	1.0000

AlphaMissense

2003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:57232144:G:C	K72N	1.000
19:57232144:G:T	K72N	1.000
19:57233518:G:T	R165I	1.000
19:57233521:A:T	D166V	1.000
19:57232056:T:C	F43S	0.999
19:57232088:T:C	F54L	0.999
19:57232090:T:A	F54L	0.999
19:57232090:T:G	F54L	0.999
19:57232092:G:A	G55E	0.999
19:57232598:T:C	L118P	0.999
19:57233518:G:C	R165T	0.999
19:57233519:A:C	R165S	0.999
19:57233519:A:T	R165S	0.999
19:57233521:A:C	D166A	0.999
19:57233521:A:G	D166G	0.999
19:57233522:T:A	D166E	0.999
19:57233522:T:G	D166E	0.999
19:57233528:G:C	K168N	0.999
19:57233528:G:T	K168N	0.999
19:57233574:G:C	D184H	0.999
19:57233575:A:C	D184A	0.999
19:57233575:A:T	D184V	0.999
19:57233576:T:A	D184E	0.999
19:57233576:T:G	D184E	0.999
19:57234966:T:A	W223R	0.999
19:57234966:T:C	W223R	0.999
19:57235014:T:C	F239L	0.999
19:57235016:T:A	F239L	0.999
19:57235016:T:G	F239L	0.999
19:57232092:G:T	G55V	0.998

dbSNP variants (sampled 300 via entrez): RS1000822226 (19:57234053 C>T), RS1001035765 (19:57229122 G>A), RS1001081046 (19:57229919 A>T), RS1001447671 (19:57232759 G>A), RS1001478401 (19:57233001 C>G), RS1002598256 (19:57230526 G>A,C), RS1003002977 (19:57230278 C>T), RS1004047148 (19:57231562 C>T), RS1004217119 (19:57229023 G>A), RS1004285802 (19:57231204 T>G), RS1004381778 (19:57235359 C>T), RS1005553769 (19:57230046 TTTTG>T), RS1005937287 (19:57229768 C>G), RS1006021555 (19:57235503 T>C), RS1006164076 (19:57233323 G>A,C)

Disease associations

OMIM: gene MIM:603495 | disease phenotypes: MIM:243060

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 5	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
spermatogenic failure 5	Definitive	AR

Mondo (1): spermatogenic failure 5 (MONDO:0009461)

Orphanet (2): Male infertility due to large-headed multiflagellar polyploid spermatozoa (Orphanet:137893), Male infertility with spermatogenesis disorder (Orphanet:399775)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0025437	Macrozoospermia
HP:0034309	Multiflagellar spermatozoa

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562903	Male Infertility with Large-Headed, Multiflagellar, Polyploid Spermatozoa (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3430911 (PROTEIN FAMILY), CHEMBL3935 (SINGLE PROTEIN), CHEMBL4106141 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

41 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 433,281 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL274654	ORANTINIB	3	3,596
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL415049	BARASERTIB	3	2,371
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL572881	MOTESANIB	3	4,642
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL105442	CI-1040	2
CHEMBL1230609	FORETINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL572878	TOZASERTIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Aurora kinase (Aur) family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
AMG-900	Inhibition	9.0	pIC50
ilorasertib	Inhibition	9.0	pIC50
GSK1070916	Inhibition	8.82	pKi
tozasertib	Inhibition	8.34	pKi
MK-5108	Inhibition	7.92	pIC50
BI-847325	Inhibition	7.82	pIC50
SU6656	Inhibition	7.77	pIC50
danusertib	Inhibition	7.21	pIC50
compound 38 [PMID: 20817473]	Inhibition	7.21	pIC50

Binding affinities (BindingDB)

26 measured of 27 human assays (27 total across all organisms); most potent 26 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
Aurora Inhibitor, 35	IC50	3.2 nM
Benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one, 1	IC50	5.6 nM
Benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one, 3	IC50	7.2 nM
Benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one, 29	IC50	13.4 nM
Benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one, 23	IC50	16.8 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
AZD1152, 33	IC50	193 nM
AMG 706	KD	300 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
SCH772984	IC50	580 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

199 potent at pChembl≥5 of 202 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL3897011
9.00	IC50	1	nM	AMG-900
9.00	Kd	1	nM	CHEMBL1822495
8.89	Kd	1.3	nM	AXITINIB
8.84	Ki	1.45	nM	GSK-1070916
8.82	Ki	1.5	nM	GSK-1070916
8.72	IC50	1.92	nM	STAUROSPORINE
8.70	Kd	2	nM	CHEMBL1822638
8.70	Kd	2	nM	CHEMBL1822637
8.62	IC50	2.42	nM	STAUROSPORINE
8.54	IC50	2.86	nM	STAUROSPORINE
8.52	IC50	3	nM	CHEMBL3393498
8.52	IC50	3	nM	CHEMBL4277690
8.52	IC50	3	nM	SNS-314
8.52	Kd	3	nM	CHEMBL1822487
8.40	Kd	4	nM	CHEMBL1822485
8.39	Kd	4.1	nM	LESTAURTINIB
8.36	Kd	4.4	nM	DEFOSBARASERTIB
8.34	Ki	4.6	nM	TOZASERTIB
8.34	IC50	4.6	nM	TOZASERTIB
8.34	Ki	4.6	nM	CHEMBL5407522
8.30	Kd	5	nM	CHEMBL1822494
8.30	Kd	5	nM	CHEMBL1822490
8.22	Kd	6	nM	CHEMBL1822491
8.22	Kd	6	nM	TOZASERTIB
8.20	Kd	6.3	nM	TOZASERTIB
8.19	IC50	6.5	nM	GSK-1070916
8.15	IC50	7	nM	ILORASERTIB
8.00	Kd	10	nM	CHEMBL1822486
7.97	Kd	10.8	nM	CHEMBL3921246
7.96	Kd	11	nM	STAUROSPORINE
7.96	Ki	11	nM	CHEMBL484950
7.94	IC50	11.4	nM	CHEMBL6169687
7.93	IC50	11.8	nM	CHEMBL6161653
7.92	IC50	12	nM	MK-5108
7.92	Kd	12	nM	FORETINIB
7.89	Kd	13	nM	CHEMBL1822488
7.85	Kd	14	nM	CHEMBL1822492
7.82	IC50	15	nM	CHEMBL3699142
7.82	IC50	15.1	nM	CHEMBL6167281
7.80	IC50	16	nM	CHEMBL5639882
7.77	Ki	17	nM	DEFOSBARASERTIB
7.77	Ki	17.03	nM	DEFOSBARASERTIB
7.77	Ki	17.03	nM	BARASERTIB
7.77	Ki	17	nM	BARASERTIB
7.77	IC50	17	nM	CHEMBL605003
7.77	IC50	17	nM	BARASERTIB
7.77	Kd	17	nM	CHEMBL1822493
7.72	IC50	19	nM	CHEMBL1086579
7.69	IC50	20.3	nM	CHEMBL6151974

PubChem BioAssay actives

189 with measured affinity, of 1001 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
N-[4-[[3-(2-aminopyrimidin-4-yl)-2-pyridinyl]oxy]phenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine	1419646: Inhibition of Aurora C kinase (unknown origin)	ic50	0.0010	uM
2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0010	uM
Axitinib	624769: Binding constant for AURKC kinase domain	kd	0.0013	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	2150976: Binding affinity to human AurC/INCENP assessed as inhibition constant using aurora sox peptide as substrate incubated for 60 mins in presence of ATP by fluorescence based assay	ki	0.0014	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715445: Inhibition of human Aurora C using [H-LRRASLG] as substrate by [gamma-33P]-ATP assay	ic50	0.0019	uM
2-[(2S,4R)-2-(hydroxymethyl)-4-[(2-methylpropan-2-yl)oxy]pyrrolidin-1-yl]-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0020	uM
2-[(2S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-1-yl]-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0020	uM
1-(3-chlorophenyl)-3-[5-[2-(thieno[2,3-d]pyrimidin-4-ylamino)ethyl]-2,3-dihydro-1,3-thiazol-2-yl]urea	1419646: Inhibition of Aurora C kinase (unknown origin)	ic50	0.0030	uM
1-(3-chlorophenyl)-3-[5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-1,3-thiazol-2-yl]urea	1902437: Inhibition of AURC (unknown origin)	ic50	0.0030	uM
ethyl (9S)-9-[3-(1H-benzimidazol-2-yloxy)phenyl]-8-oxo-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinoline-3-carboxylate	1189502: Inhibition of poly-histidine tagged full length recombinant aurora C (unknown origin) assessed as phosphorylation of NuMA-histidine substrate by scintillation counting analysis	ic50	0.0030	uM
N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]-6-[(2-morpholin-4-ylacetyl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0030	uM
N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0040	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507838: Binding affinity to AURKC	kd	0.0041	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	436006: Binding constant for full-length AURKC	kd	0.0044	uM
N-[4-[4-(4-aminopiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	1977331: Inhibition of human N-terminal His-tagged aurora C assessed as inhibition constant incubated for 15 mins using Histone H3 as substrate in presence [gamma32P]-ATP by scintillation counter method	ki	0.0046	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	1126524: Inhibition of N-terminal His-6-tagged recombinant Aurora 3 (1 to 309) (unknown origin) expressed in baculovirus expression system by radiometric assay	ki	0.0046	uM
2-(dimethylamino)-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0050	uM
N-[4-[6-[[2-(4-methylpiperazin-1-yl)-2-oxoacetyl]amino]-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0050	uM
2-(cyclopropylamino)-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0060	uM
1-[4-[4-amino-7-[1-(2-hydroxyethyl)pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl]phenyl]-3-(3-fluorophenyl)urea	1676612: Inhibition of AuroraC (unknown origin)	ic50	0.0070	uM
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	1799704: In Vitro Kinase Assay from Article 10.1021/cb200305u: “Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen.”	ic50	0.0091	uM
N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]-6-(3-piperidin-1-ylpropanoylamino)pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0100	uM
2-[(3R)-3-(3,3-difluoropyrrolidine-1-carbonyl)pyrrolidin-1-yl]-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide	698813: Binding affinity to Aurora kinase C	kd	0.0100	uM
(3R)-N-cyclopentyl-1-[2-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylanilino]-2-oxoethyl]pyrrolidine-3-carboxamide	698813: Binding affinity to Aurora kinase C	kd	0.0100	uM
6-[[4-[(Z)-[2-(4-ethylphenyl)imino-3-methyl-4-oxo-1,3-thiazolidin-5-ylidene]methyl]-2-pyridinyl]amino]pyridine-3-carboxylic acid	1323333: Binding affinity to human Aurora C kinase expressed in Escherichia coli BL21 cells incubated for 1 hr by active site directed binding competition assay	kd	0.0108	uM
N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl]sulfanylphenyl]acetamide	420297: Inhibition of Aurora-C	ki	0.0110	uM
4-(3-chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)-2-pyridinyl]methyl]cyclohexane-1-carboxylic acid	1331761: Inhibition of human recombinant full-length N-terminal GST-tagged Aurora C (1 to 275 end residues) expressed in baculovirus expression system using GLRRASLG-NH2 as substrate after 20 mins in presence of [gamma-33P]-ATP by liquid scintillation counting	ic50	0.0120	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624769: Binding constant for AURKC kinase domain	kd	0.0120	uM
N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]-6-[(2-pyrrolidin-1-ylacetyl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0130	uM
2-(cyclopentylamino)-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0140	uM
3-[3-[N-[4-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-1H-indol-6-yl]-N-ethylprop-2-ynamide	1942484: Inhibition of human Aurora C	ic50	0.0150	uM
6-fluoro-N-[(6-fluoro-2-methoxy-3-pyridinyl)methyl]-5-[(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyridin-2-amine	2141401: Inhibition of human AURKC by discoverX kinome scan assay	ic50	0.0160	uM
2-[ethyl-[3-[4-[[5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl]amino]quinazolin-7-yl]oxypropyl]amino]ethyl dihydrogen phosphate	2193872: Inhibition of human aurora C	ki	0.0170	uM
(3Z)-N,N-dimethyl-2-oxo-3-(4,5,6,7-tetrahydro-1H-indol-2-ylmethylidene)-1H-indole-5-sulfonamide	435568: Inhibition of Aurora C in the presence of 5uM ATP	ic50	0.0170	uM
N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]-2-morpholin-4-ylacetamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0170	uM
3-[[4-[6-bromo-2-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-b]pyridin-7-yl]piperazin-1-yl]methyl]-5-methyl-1,2-oxazole	482306: Inhibition of human recombinant Aurora C expressed in baculovirus system	ic50	0.0190	uM
N-[4-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]-N’-hydroxyoctanediamide	1469369: Inhibition of recombinant human N-terminal His6-tagged Aurora-C (35-end residues)/N-terminal GST-tagged INCENP (821-end residues) expressed in baculovirus infected sf21 cells using AKRRRLSSLRA substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method	ic50	0.0220	uM
2-[4-(4-hydroxypiperidin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1799704: In Vitro Kinase Assay from Article 10.1021/cb200305u: “Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen.”	ic50	0.0246	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624769: Binding constant for AURKC kinase domain	kd	0.0330	uM
5,11-dimethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimido[4,5-b][1,4]benzodiazepin-6-one	1799704: In Vitro Kinase Assay from Article 10.1021/cb200305u: “Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen.”	ic50	0.0405	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624769: Binding constant for AURKC kinase domain	kd	0.0410	uM
4-(propanoylamino)-N-[4-[(5,8,11-trimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]phenyl]benzamide	1371469: Inhibition of recombinant full length GST-tagged human Aurora C expressed in baculovirus expression system by Z’LYTE assay	ic50	0.0530	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624769: Binding constant for AURKC kinase domain	kd	0.0590	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1189495: Inhibition of aurora C (unknown origin)	ic50	0.0610	uM
3-[(4-morpholin-4-ylbenzoyl)amino]-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]-1H-thieno[3,2-c]pyrazole-5-carboxamide	517180: Inhibition of aurora C	ic50	0.0620	uM
4-(prop-2-enoylamino)-N-[4-[(5,8,11-trimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]phenyl]benzamide	1371469: Inhibition of recombinant full length GST-tagged human Aurora C expressed in baculovirus expression system by Z’LYTE assay	ic50	0.0630	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	353623: Inhibition of aurora C kinase	ic50	0.0650	uM
N-(4-fluorophenyl)-N’-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-6-yl]propanediamide	1184096: Inhibition of Aurora C (unknown origin) using H-LRRASLG substrate by radioisotope-based P81 filter-binding assay	ic50	0.0672	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	436006: Binding constant for full-length AURKC	kd	0.0710	uM
N-[4-[6-[[2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]acetyl]amino]-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	616643: Binding affinity to Aurora C kinase catalytic domain by competitive binding assay	kd	0.0800	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Glyphosate	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Vehicle Emissions	affects methylation, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Berberine	increases expression	1
Carbamazepine	affects expression	1
Nitrogen Dioxide	affects methylation, increases abundance	1
Phenylmercuric Acetate	decreases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Silver	increases expression, increases reaction	1
Silver Nitrate	increases expression, increases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	increases expression	1
Asbestos, Serpentine	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1

ChEMBL screening assays

358 unique, capped per target: 358 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3887043	Binding	HTRF Assay: The effect of the compounds of the invention on the activity of the enzyme PDE3 was evaluated by the company CEREP (Le bois I’Evêque, 86600 Celle I’Evescault, France; http://www.cerep.fr) in accordance with its standard protocol	Anti-cancer compound and pharmaceutical composition containing the same

Clinical trials (associated diseases)

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