HASPIN

Summary

HASPIN (histone H3 associated protein kinase, HGNC:19682) is a protein-coding gene on chromosome 17p13.2, encoding Serine/threonine-protein kinase haspin (Q8TF76). Serine/threonine-protein kinase that phosphorylates histone H3 at ‘Thr-3’ (H3T3ph) during mitosis.

Enables ATP binding activity and histone H3T3 kinase activity. Involved in several processes, including mitotic sister chromatid cohesion; mitotic spindle assembly checkpoint signaling; and protein localization to chromosome, centromeric region. Located in centrosome; nucleoplasm; and spindle.

Source: NCBI Gene 83903 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 135 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 8 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 6 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_031965
• Notable: 135 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19682
Approved symbol	HASPIN
Name	histone H3 associated protein kinase
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177602
Ensembl biotype	protein_coding
OMIM	609240
Entrez	83903

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000325418

ENST00000325418

RefSeq mRNA: 1 — MANE Select: NM_031965 NM_031965

CCDS: CCDS11036

Canonical transcript exons

ENST00000325418 — 1 exons

Exon	Start	End
ENSE00001287270	3723903	3726699

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 88.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8709 / max 92.6940, expressed in 1267 samples.

Highest expression (Bgee): pancreatic ductal cell, secondary oocyte, oocyte, ventricular zone, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HASPIN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	7.5e-28	-0.40	17:3716272:CAG:C
Cells EBV-transformed lymphocytes	eqtl	6.8e-14	+0.30	17:3727327:G:A
Testis	eqtl	4.5e-11	+0.17	17:3726554:A:G
Spleen	eqtl	3.4e-05	+1.99	17:2948737:C:G
Artery Tibial	eqtl	3.2e-02	-0.46	17:3737080:G:A
Kidney Cortex	eqtl	3.3e-02	-0.48	17:2928798:T:C
Lung	eqtl	3.4e-02	+0.22	17:3801189:G:A
Brain Hypothalamus	eqtl	4.6e-02	-0.90	17:4325652:T:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
158882	7.8709	1267

Top tissues by expression

showing 100 of 241 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	88.06	silver quality
secondary oocyte	CL:0000655	84.83	gold quality
oocyte	CL:0000023	79.81	gold quality
ventricular zone	UBERON:0003053	77.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.89	gold quality
tibialis anterior	UBERON:0001385	73.44	silver quality
ganglionic eminence	UBERON:0004023	72.58	gold quality
kidney epithelium	UBERON:0004819	72.08	gold quality
bone marrow cell	CL:0002092	71.95	gold quality
sperm	CL:0000019	71.15	gold quality
upper arm skin	UBERON:0004263	71.14	gold quality
ileal mucosa	UBERON:0000331	69.97	gold quality
stromal cell of endometrium	CL:0002255	68.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.49	gold quality
left testis	UBERON:0004533	67.30	gold quality
right testis	UBERON:0004534	67.12	gold quality
testis	UBERON:0000473	66.65	gold quality
vermiform appendix	UBERON:0001154	65.99	gold quality
bone marrow	UBERON:0002371	65.76	gold quality
lymph node	UBERON:0000029	64.47	gold quality
buccal mucosa cell	CL:0002336	63.40	gold quality
rectum	UBERON:0001052	62.06	gold quality
deltoid	UBERON:0001476	61.96	silver quality
colonic epithelium	UBERON:0000397	61.80	gold quality
caecum	UBERON:0001153	61.48	gold quality
mucosa of transverse colon	UBERON:0004991	61.13	gold quality
lower esophagus mucosa	UBERON:0035834	60.41	gold quality
quadriceps femoris	UBERON:0001377	60.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	59.85	gold quality
esophagus mucosa	UBERON:0002469	59.68	gold quality
tonsil	UBERON:0002372	59.53	gold quality
spleen	UBERON:0002106	59.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	59.45	gold quality
gingival epithelium	UBERON:0001949	58.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	58.63	gold quality
vastus lateralis	UBERON:0001379	58.43	gold quality
nasal cavity epithelium	UBERON:0005384	57.92	gold quality
small intestine	UBERON:0002108	57.77	gold quality
lower lobe of lung	UBERON:0008949	56.96	silver quality
skin of hip	UBERON:0001554	56.16	gold quality
islet of Langerhans	UBERON:0000006	56.04	gold quality
cerebellar vermis	UBERON:0004720	56.02	gold quality
epithelium of nasopharynx	UBERON:0001951	56.00	gold quality
endothelial cell	CL:0000115	55.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	55.90	gold quality
gastrocnemius	UBERON:0001388	55.63	gold quality
muscle of leg	UBERON:0001383	55.21	gold quality
substantia nigra pars reticulata	UBERON:0001966	54.40	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
body of stomach	UBERON:0001161	53.80	gold quality
upper lobe of lung	UBERON:0008948	53.66	gold quality
adult organism	UBERON:0007023	53.55	silver quality
gingiva	UBERON:0001828	53.46	gold quality
upper leg skin	UBERON:0004262	53.45	silver quality
upper lobe of left lung	UBERON:0008952	53.43	gold quality
muscle tissue	UBERON:0002385	53.41	gold quality
transverse colon	UBERON:0001157	53.39	gold quality
skeletal muscle tissue	UBERON:0001134	53.37	gold quality
smooth muscle tissue	UBERON:0001135	53.31	gold quality
stomach	UBERON:0000945	53.20	gold quality
granulocyte	CL:0000094	52.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	52.79	silver quality
leukocyte	CL:0000738	52.24	silver quality
monocyte	CL:0000576	52.05	silver quality
placenta	UBERON:0001987	51.97	gold quality
lung	UBERON:0002048	51.78	gold quality
duodenum	UBERON:0002114	51.63	gold quality
endometrium	UBERON:0001295	51.59	gold quality
trabecular bone tissue	UBERON:0002483	51.02	gold quality
adrenal tissue	UBERON:0018303	50.76	gold quality
myocardium	UBERON:0002349	50.25	gold quality
blood	UBERON:0000178	50.11	gold quality
subthalamic nucleus	UBERON:0001906	49.97	gold quality
right uterine tube	UBERON:0001302	49.84	gold quality
right lung	UBERON:0002167	49.65	gold quality
intestine	UBERON:0000160	49.39	gold quality
gall bladder	UBERON:0002110	48.97	gold quality
esophagus	UBERON:0001043	48.16	gold quality
lateral globus pallidus	UBERON:0002476	47.79	gold quality
biceps brachii	UBERON:0001507	47.77	gold quality
dorsal plus ventral thalamus	UBERON:0001897	47.54	gold quality
mouth mucosa	UBERON:0003729	47.10	gold quality
minor salivary gland	UBERON:0001830	47.02	gold quality
pancreas	UBERON:0001264	47.01	gold quality
nasal cavity mucosa	UBERON:0001826	46.93	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	46.62	gold quality
skin of abdomen	UBERON:0001416	46.42	gold quality
saliva-secreting gland	UBERON:0001044	46.33	gold quality
large intestine	UBERON:0000059	46.30	gold quality
colon	UBERON:0001155	46.30	gold quality
vagina	UBERON:0000996	46.13	gold quality
urinary bladder	UBERON:0001255	46.07	gold quality
zone of skin	UBERON:0000014	45.32	gold quality
skin of leg	UBERON:0001511	45.29	gold quality
fundus of stomach	UBERON:0001160	45.26	gold quality
ventral tegmental area	UBERON:0002691	44.80	gold quality
uterus	UBERON:0000995	44.72	gold quality
female reproductive system	UBERON:0000474	44.52	gold quality
liver	UBERON:0002107	44.18	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.92

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	6.8	high
Bone marrow	tissue	5.7	low
Thymus	tissue	5.0
Tonsil	tissue	4.8	low
Lymph node	tissue	3.9	not detected
Spinal cord	tissue	1.9
Appendix	tissue	1.7	low
Small intestine	tissue	1.4	not detected
Duodenum	tissue	1.4	not detected
Corpus callosum	tissue	1.4
Amygdala	tissue	1.3
Medulla oblongata	tissue	1.3
Substantia nigra	tissue	1.3
Periaqueductal gray	tissue	1.3
Hypothalamus	tissue	1.2
Hippocampal formation	tissue	1.2
Septum	tissue	1.2
Pons	tissue	1.1
Basal ganglia	tissue	1.1	low
Putamen	tissue	1.1
Midbrain	tissue	1.1
Ventral forebrain	tissue	1.1
Cerebral cortex	tissue	1.0	low
Rectum	tissue	1.0	low
Colon	tissue	1.0	low
Thalamus	tissue	1.0
Insular cortex	tissue	1.0
Spleen	tissue	0.9	low
Retrosplenial cortex	tissue	0.9
Prefrontal cortex	tissue	0.8
Stomach 1	tissue	0.8	low
Motor cortex	tissue	0.8
Entorhinal cortex	tissue	0.8
Temporal cortex	tissue	0.8
Choroid plexus	tissue	0.7
Retrosplenial and cingulate cortex	tissue	0.7
Olfactory bulb	tissue	0.7
Skin 1	tissue	0.6	medium
Esophagus	tissue	0.6	medium
Superior colliculi	tissue	0.6
Placenta	tissue	0.6	medium
Somatosensory cortex	tissue	0.6
Occipital cortex	tissue	0.6
Vagina	tissue	0.5	medium
Nucleus accumbens	tissue	0.4
Breast	tissue	0.3	medium
Salivary gland	tissue	0.3	low
Skeletal muscle	tissue	0.3	medium
Smooth muscle	tissue	0.3	medium
Urinary bladder	tissue	0.3	low
Cerebellum	tissue	0.3	low
Lung	tissue	0.3	medium
Ovary	tissue	0.2	medium
Endometrium 1	tissue	0.2	low
Gallbladder	tissue	0.2	medium
Locus coeruleus	tissue	0.2
Hippocampus	tissue	0.2	low
Postcentral gyrus	tissue	0.2
Caudate putamen	tissue	0.2
Cervix	tissue	0.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Ventral spinal cord (1.9), Dorsal spinal cord (1.4), White matter (1.4), Subiculum (1.2), Ventral hippocampus (1.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

29 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-649	97.96	67.21	704
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-4703-3P	96.68	68.61	545
HSA-MIR-5090	93.28	60.86	94
HSA-MIR-6775-5P	92.43	61.00	132
HSA-MIR-6727-5P	92.41	61.98	83

Functional genomics

gnomAD constraint: pLI 6.8e-08, LOEUF 1.07, missense Z 0.103 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000325418 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:3,723,936–3,725,908	881 / 845.5	1.04	no
17:3,725,909–3,725,954	6 / 16.9	0.36	yes (p 8.0e-03)
17:3,725,955–3,726,329	129 / 156.2	0.83	no

Literature-anchored findings (GeneRIF, showing 31)

• This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis (PMID:15681610)
• Haspin is required to maintain centromeric cohesion during mitosis. (PMID:17084365)
• Haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion. (PMID:19910498)
• Haspin is a relatively newly discovered kinase that phosphorylates histone H3 during mitosis and appears to play a role in regulating chromosome behavior during cell division. [REVIEW] (PMID:19997740)
• phosphorylation of H3T3 by Haspin is necessary for chromosomal passenger complex(CPC) accumulation at centromeres; Survivin binds to H3T3ph; H3T3ph generated by Haspin positions CPC at centromeres to regulate selected targets of Aurora B during mitosis (PMID:20705812)
• findings show phosphorylation of histone H3-threonine 3 mediated by Haspin cooperates with Bub1-mediated histone 2A-serine 121 phosphorylation in targeting the chromosomal passenger complex to the inner centromere in fission yeast and human cells (PMID:20929775)
• Aurora B phosphorylates Haspin to promote generation of H3T3ph and that Aurora B kinase activity is required for normal chromosomal localization of the CPC, indicating an intimate linkage between Aurora B and Haspin functions in mitosis (PMID:21658950)
• Haspin inhibitors reveal centromeric roles of Aurora B in chromosome movement and spindle checkpoint signaling (PMID:23071152)
• Haspin activity affects the phosphorylation state of proteins involved in gene expression regulation and splicing. (PMID:24732914)
• Haspin kinase plays a key role in maintaining the slowly exchanging centromere Borealin pool. (PMID:25854549)
• This is the first structural model of a bisubstrate inhibitor targeting haspin. The presented structural data represent a model for the future development of more specific haspin inhibitors (PMID:27139824)
• The mitotic histone kinase Haspin binds to the cohesin regulatory subunit Pds5B through a conserved YGA/R motif in its non-catalytic N terminus, which is similar to the recently reported YSR-motif-dependent binding of Wapl to Pds5B. (PMID:28343965)
• The authors’ data identify the HIM of Pds5 as a binding motif for Haspin/Hrk1 in fission yeast. The authors’ analyses also show that human PDS5B binds Haspin through the same HIM-PIM interaction module, indicating that the Haspin localization mechanism is highly conserved. (PMID:28343969)
• Autosomal recessive RP associated with mutations in the male germ cell-associated kinase (MAK) gene is associated with preservation of foveal vision even in advanced stages of retinal degeneration despite similar rates of peripheral visual field loss to other forms of autosomal recessive RP (PMID:29103961)
• The results indicate a kinase-dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis. (PMID:29138236)
• GSG2 upregulation was associated with pancreatic cancer progression. (PMID:31493385)
• HASPIN is involved in the progression of gallbladder carcinoma. (PMID:31987787)
• Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis. (PMID:32027339)
• Genome-wide CRISPR screen uncovers a synergistic effect of combining Haspin and Aurora kinase B inhibition. (PMID:32300176)
• Knockdown of GSG2 inhibits prostate cancer progression in vitro and in vivo. (PMID:32319597)
• GSG2 (Haspin) promotes development and progression of bladder cancer through targeting KIF15 (Kinase-12). (PMID:32439830)
• GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration. (PMID:33846801)
• Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation. (PMID:34299370)
• Loss of haspin suppresses cancer cell proliferation by interfering with cell cycle progression at multiple stages. (PMID:34551143)
• Knockdown of GSG2 Suppresses the Progression of Colorectal Cancer Cells. (PMID:35089075)
• Effects and mechanisms of GSG2 in esophageal cancer progression. (PMID:35939116)
• Knockdown of GSG2 inhibits the development and progression of non-small cell lung cancer in vitro and in vivo. (PMID:35972887)
• GSG2 facilitates the progression of human breast cancer through MDM2-mediated ubiquitination of E2F1. (PMID:37537694)
• GSG2 promotes thyroid cancer via stabilizing AURKB and activating AKT pathway. (PMID:38441546)
• Germ cell-specific gene 2 accelerates cell cycle in epithelial ovarian cancer by inhibiting GSK3alpha-p27 cascade. (PMID:38613588)
• GSG2 promotes progression of human endometrial cancer by regulating PD-1/PD-L1 expression via PI3K-AKT pathway. (PMID:38759367)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	haspin	ENSDARG00000092290
mus_musculus	Haspin	ENSMUSG00000050107
rattus_norvegicus	Haspin	ENSRNOG00000048660
drosophila_melanogaster	pll	FBGN0010441
drosophila_melanogaster	Haspin	FBGN0046706
caenorhabditis_elegans		WBGENE00004029
caenorhabditis_elegans	hasp-1	WBGENE00007258
caenorhabditis_elegans		WBGENE00012159
caenorhabditis_elegans	hasp-2	WBGENE00021214

Paralogs (4): IRAK3 (ENSG00000090376), IRAK2 (ENSG00000134070), IRAK1 (ENSG00000184216), IRAK4 (ENSG00000198001)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1194498) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal male germ cell morphology	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
Bos taurus	Q2KIP2	66.5%	Diamond
Arabidopsis thaliana	O80528	40.3%	Diamond
Schizosaccharomyces pombe 972h-	O13924	35.9%	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
CTNS	protein-coding	1497
SHPK	protein-coding	23729
TAX1BP3	protein-coding	30851
ITGAE	protein-coding	3682
P2RX5	protein-coding	5026
NCBP3	protein-coding	55421
EMC6	protein-coding	83460
P2RX5-TAX1BP3	ncRNA	100533970
P2RX1	protein-coding	5023
CAMKK1	protein-coding	84254

Protein

Protein identifiers

Serine/threonine-protein kinase haspin — Q8TF76 (reviewed: Q8TF76)

Alternative names: Germ cell-specific gene 2 protein, H-haspin, Haploid germ cell-specific nuclear protein kinase

All UniProt accessions (1): Q8TF76

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that phosphorylates histone H3 at ‘Thr-3’ (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.

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

Tissue specificity. Strongly expressed in testis. Also present in thymus and bone marrow and low levels observed in prostate, intestine, lung, spleen and lymph node. Expressed in fetal skin, liver, kidney and small intestine and also in proliferating but not non-proliferating cell lines.

Post-translational modifications. Autophosphorylated on both serine and threonine residues. Strongly phosphorylated during mitosis but this does not appear to significantly affect its intrinsic kinase activity. Phosphorylation by AURKB is required for full activity toward histone H3 at ‘Ser-3’ in mitosis.

Activity regulation. Constitutive activity that does not require phosphorylation. Specifically inhibited by 3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine (CHR-6494).

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TF76-1	1	yes
Q8TF76-2	2

RefSeq proteins (1): NP_114171* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR024604	GSG2_C	Domain

Pfam: PF12330

Catalyzed reactions (Rhea)

• 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 (76 total): strand 19, helix 18, sequence variant 10, mutagenesis site 7, binding site 5, modified residue 5, splice variant 2, region of interest 2, sequence conflict 2, compositionally biased region 2, chain 1, domain 1, turn 1, active site 1

Structure

Experimental structures (PDB)

showing 30 of 43 structures by resolution:

PDB	Title	Method	Resolution (Å)
4QTC	Structure of human haspin (GSG2) in complex with SCH772984 revealing the first type-I …	X-RAY DIFFRACTION	1.4
6G3A	Crystal structure of haspin F605T mutant in complex with 5-iodotubercidin	X-RAY DIFFRACTION	1.43
6G39	Crystal structure of haspin F605Y mutant in complex with 5-iodotubercidin	X-RAY DIFFRACTION	1.45
6G36	Crystal structure of haspin in complex with 5-chlorotubercidin	X-RAY DIFFRACTION	1.46
6G38	Crystal structure of haspin in complex with tubercidin	X-RAY DIFFRACTION	1.47
6G37	Crystal structure of haspin in complex with 5-fluorotubercidin	X-RAY DIFFRACTION	1.48
5HTC	Crystal structure of haspin (GSG2) in complex with bisubstrate inhibitor ARC-3372	X-RAY DIFFRACTION	1.5
6Z57	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2004078	X-RAY DIFFRACTION	1.5
6Z5E	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2004093	X-RAY DIFFRACTION	1.5
6G35	Crystal structure of haspin in complex with 5-bromotubercidin	X-RAY DIFFRACTION	1.55
6Z5A	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2002941	X-RAY DIFFRACTION	1.55
7AVQ	Crystal structure of haspin in complex with disubstituted imidazo[1,2- b]pyridazine …	X-RAY DIFFRACTION	1.65
5HTB	Crystal structure of haspin (GSG2) in complex with bisubstrate inhibitor ARC-3353.	X-RAY DIFFRACTION	1.7
24UH	Crystal structure of Haspin (GSG2) with an ATP-mimicking competitive inhibitor	X-RAY DIFFRACTION	1.73
6Z5C	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2004070	X-RAY DIFFRACTION	1.75
6Z5D	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2004082	X-RAY DIFFRACTION	1.75
6G34	Crystal structure of haspin in complex with 5-iodotubercidin	X-RAY DIFFRACTION	1.76
7SQM	Discovery and Preclinical Pharmacology of INE963, A Potent and Fast-Acting Blood-Stage …	X-RAY DIFFRACTION	1.78
2VUW	Structure of human haspin kinase domain	X-RAY DIFFRACTION	1.8
3F2N	Crystal Structure of Human Haspin with an Imidazo-pyridazine ligand	X-RAY DIFFRACTION	1.8
6Z58	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2003791	X-RAY DIFFRACTION	1.8
3DLZ	Crystal structure of human haspin in complex with AMP	X-RAY DIFFRACTION	1.85
9FLQ	Crystal structure of human Haspin (GSG2) kinase bound to MU1959	X-RAY DIFFRACTION	1.85
24WC	Crystal structure of Haspin (GSG2) with an ATP-mimicking inhibitor LJ-5242	X-RAY DIFFRACTION	1.88
4OUC	Structure of human haspin in complex with histone H3 substrate	X-RAY DIFFRACTION	1.9
6Z56	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2003208	X-RAY DIFFRACTION	1.9
6Z5B	Crystal structure of haspin (GSG2) in complex with macrocycle ODS2003128	X-RAY DIFFRACTION	1.9
9FLR	Crystal structure of human Haspin (GSG2) kinase bound to MU1963	X-RAY DIFFRACTION	1.91
3E7V	Crystal Structure of Human Haspin with a pyrazolo-pyrimidine ligand	X-RAY DIFFRACTION	2
3FMD	Crystal Structure of Human Haspin with an Isoquinoline ligand	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF76-F1	63.64	0.41

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · 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.

Catalytic / active sites (1)

Position	Role
649	proton acceptor

Ligand- & substrate-binding residues (5)

Position	Role
649–654	ATP
687–689	ATP
490–498	ATP
511	ATP
606–611	ATP

Post-translational modifications (5)

Type	Positions
Phosphoserine	58, 93, 143, 147
Phosphothreonine	97

Mutagenesis-validated functional residues (7)

Position	Phenotype
492	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
511	strongly reduced enzyme activity.
651	strongly reduced enzyme activity, markedly reduced affinity for histone h3.
707	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
709	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
713	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
716	markedly reduced histone h3 phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 207 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CHROMOSOME_SEPARATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOLDRATH_ANTIGEN_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME_CENTROMERIC_REGION, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_SISTER_CHROMATID_COHESION, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (10): mitotic cell cycle (GO:0000278), protein phosphorylation (GO:0006468), mitotic sister chromatid cohesion (GO:0007064), mitotic spindle assembly checkpoint signaling (GO:0007094), intracellular signal transduction (GO:0035556), protein localization to chromosome, centromeric region (GO:0071459), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), chromosome organization (GO:0051276), negative regulation of mitotic cell cycle phase transition (GO:1901991)

GO Molecular Function (10): protein kinase activity (GO:0004672), ATP binding (GO:0005524), histone H3T3 kinase activity (GO:0072354), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), histone kinase activity (GO:0035173)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819)

GO top-level categories

41 GO namespaces:

Category	Terms
protein kinase activity	3
intracellular anatomical structure	2
cellular anatomical structure	2
intracellular membraneless organelle	2
cell cycle	1
mitotic nuclear division	1
phosphorylation	1
protein modification process	1
sister chromatid cohesion	1
mitotic cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
signal transduction	1
protein localization to chromosome	1
cellular component organization	1
chromatin organization	1
organelle organization	1
mitotic cell cycle phase transition	1
negative regulation of mitotic cell cycle	1
negative regulation of cell cycle phase transition	1
regulation of mitotic cell cycle phase transition	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
anion binding	1
protein serine/threonine kinase activity	1
histone H3 kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
histone modifying activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
intracellular signal transduction	BP	direct assay
mitotic sister chromatid cohesion	BP	mutant phenotype
mitotic spindle assembly checkpoint signaling	BP	mutant phenotype
protein localization to chromosome, centromeric region	BP	mutant phenotype
protein phosphorylation	BP	direct assay
centrosome	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
spindle	CC	direct assay
ATP binding	MF	direct assay
histone H3T3 kinase activity	MF	mutant phenotype
protein kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,152 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HASPIN	AURKB	Q96GD4	894
HASPIN	BUB1	O43683	893
HASPIN	PDS5A	Q29RF7	845
HASPIN	KIF2C	Q99661	812
HASPIN	H3-3A	P06351	800
HASPIN	H3C1	P02295	800
HASPIN	H3-4	Q16695	800
HASPIN	H3-7	Q5TEC6	800
HASPIN	H3-5	Q6NXT2	800
HASPIN	H3C14	Q71DI3	800
HASPIN	BIRC5	O15392	797
HASPIN	SGO1	Q5FBB7	784
HASPIN	INCENP	Q9NQS7	764
HASPIN	RCC2	Q9P258	758
HASPIN	H2AC19	P20670	740

IntAct

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

7 partners by confidence:

Partner	Interaction type	MIscore	Records
HSF2BP	physical association	0.560	3
MDFI	physical association	0.560	3
HSP90AB1	physical association	0.520	2
H3-3A	phosphorylation reaction	0.440	1
KPNA6	association	0.350	1
MYO1C	association	0.350	1
TP73	association	0.350	1

SIGNOR signaling

showing 5 of 10 signaling interactions:

A	Effect	B	Mechanism
AURKB	“up-regulates activity”	HASPIN	phosphorylation
HASPIN	“up-regulates activity”	H3C1	phosphorylation
CDK1	“up-regulates activity”	HASPIN	phosphorylation
HASPIN	“up-regulates activity”	PLK1	binding
PLK1	“up-regulates activity”	HASPIN	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for HASPIN: 135 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	12
Benign	0

SpliceAI

Top 7 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 7 predictions of 7):

Position(s)	Effect	Δscore	Sites
17:3724663	donor_gain	0.4100
17:3725719	acceptor_gain	0.3400
17:3725482	acceptor_gain	0.2900
17:3725052	acceptor_gain	0.2500
17:3724663	donor_gain	0.2400
17:3725362	acceptor_gain	0.2400
17:3725362	acceptor_gain	0.2100

AlphaMissense

1,007 missense substitutions predicted likely pathogenic (of 5,222 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
M725	9	0.913	0.990
D687	8	0.995	0.999
D649	8	0.991	0.998
H647	8	0.986	0.996
N654	8	0.976	0.993
H651	8	0.972	0.992
F645	8	0.963	0.997
F499	8	0.951	0.996
F556	8	0.951	0.997
F711	8	0.941	0.989
N741	8	0.929	0.996
F797	8	0.925	0.980
F475	8	0.922	0.986
D716	8	0.909	0.958
W744	7	0.987	0.998
W577	7	0.986	0.995
W733	7	0.982	0.997
F600	7	0.974	0.991
K511	7	0.971	0.997
E646	7	0.971	0.989

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	7.25e-05
Bladder Urothelial Carcinoma (TCGA)	unfavorable	0.000969

Disease associations

OMIM: gene MIM:609240 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST012431_8	Parkinson’s disease	2e-15
GCST012431_14	Parkinson’s disease	1e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075163 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,137 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

6 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL5173264	INE-963	2	6
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	4
CHEMBL269538	HARMINE	1	4,500
CHEMBL4225966	SEL-120 FREE BASE	1	99
CHEMBL4076837	SENEXIN B	1	109
CHEMBL1952329	SGI-1776	1	419

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Haspin family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
SGI-1776	Inhibition	7.47	pIC50

Binding affinities (BindingDB)

215 measured of 304 human assays (325 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5563118	IC50	0.002 nM
ARC-3429	KD	0.019 nM
CHEMBL5199572	KD	0.019 nM
CHEMBL5440655	IC50	0.024 nM
CHEMBL5574302	IC50	0.035 nM
CHEMBL5576026	IC50	0.084 nM
ARC-3430	KD	0.1 nM
CHEMBL5574055	IC50	0.155 nM
CHEMBL5194339	KD	0.42 nM
CHEMBL4066819	IC50	0.46 nM
5-cyclopropyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	0.48 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	0.77 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	0.827 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.09 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3,7,7-trimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
13-chloro-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(13),2(6),4,9,11-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7S)-7-cyclohexyl-3-ethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7R)-7-cyclohexyl-3-ethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-chloro-3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	2.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-cyclopropyl-3-ethyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	2.65 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
CHEMBL5201780	IC50	3 nM
CHEMBL5563528	IC50	3 nM
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxylic acid	IC50	3.01 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-1’-(2,2,2-trifluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	3.14 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
4-[2-[6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl]ethylamino]quinoline-6-carbonitrile	IC50	3.6 nM	US-12281080: Quinoline-based compounds and methods of inhibiting CDK8/19
CHEMBL5169980	KD	4 nM
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	4.58 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-(2-chloro-4-pyridinyl)-N-[(4-fluoropiperidin-4-yl)methyl]-4-methyl-13-oxa-3,6,7-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7-tetraen-8-amine	IC50	4.8 nM	US-20240199630: IMIDAZO[1,2-B]PYRIDAZINE BASED TRICYCLIC COMPOUNDS AS INHIBITORS OF HASPIN AND THERAPEUTIC USES THEREOF
CHEMBL5201904	IC50	5 nM
CHEMBL5575484	IC50	5 nM
[1-[5-(2-chloro-4-pyridinyl)-4-methyl-13-oxa-3,6,7-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7-tetraen-8-yl]piperidin-3-yl]methanamine	IC50	5.03 nM	US-20240199630: IMIDAZO[1,2-B]PYRIDAZINE BASED TRICYCLIC COMPOUNDS AS INHIBITORS OF HASPIN AND THERAPEUTIC USES THEREOF
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
(11S)-5-(2-chloro-4-pyridinyl)-N-[(4-fluoropiperidin-4-yl)methyl]-4,11-dimethyl-12-oxa-3,6,7-triazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-8-amine	IC50	5.87 nM	US-20240199630: IMIDAZO[1,2-B]PYRIDAZINE BASED TRICYCLIC COMPOUNDS AS INHIBITORS OF HASPIN AND THERAPEUTIC USES THEREOF
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	6.1 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-(2-chloro-4-pyridinyl)-N-[(4-fluoropiperidin-4-yl)methyl]-4,11-dimethyl-12-oxa-3,6,7-triazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-8-amine	IC50	6.37 nM	US-20240199630: IMIDAZO[1,2-B]PYRIDAZINE BASED TRICYCLIC COMPOUNDS AS INHIBITORS OF HASPIN AND THERAPEUTIC USES THEREOF
Staurosporine, 8	IC50	6.5 nM
CHEMBL1952141	IC50	7 nM
CHEMBL5566424	IC50	7 nM
(7S)-7-cyclohexyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	7.14 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
1’-acetylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	7.48 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	8.22 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
[(3S)-1-[5-(2-chloro-4-pyridinyl)-4-methyl-13-oxa-3,6,7-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7-tetraen-8-yl]piperidin-3-yl]methanamine	IC50	10.2 nM	US-20240199630: IMIDAZO[1,2-B]PYRIDAZINE BASED TRICYCLIC COMPOUNDS AS INHIBITORS OF HASPIN AND THERAPEUTIC USES THEREOF
ARC-3384	KD	11 nM
3-(2-methoxyethyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	11.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	11.9 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors

ChEMBL bioactivities

243 potent at pChembl≥5 of 251 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.72	Kd	0.019	nM	CHEMBL5199572
9.81	IC50	0.155	nM	CHEMBL5574055
9.38	Kd	0.42	nM	CHEMBL5194339
9.26	Kd	0.55	nM	CHEMBL5440655
8.80	IC50	1.6	nM	CHEMBL4791276
8.70	IC50	2	nM	CHEMBL5178368
8.52	IC50	3	nM	CHEMBL5201780
8.52	IC50	3	nM	CHEMBL5186093
8.52	IC50	3	nM	CHEMBL5178368
8.52	IC50	3	nM	CHEMBL5563528
8.40	IC50	4	nM	CHEMBL4064608
8.40	Kd	4	nM	CHEMBL5169980
8.40	IC50	4	nM	CHEMBL5178368
8.30	IC50	5	nM	CHEMBL5201904
8.30	IC50	5	nM	IODOTUBERCIDIN
8.30	IC50	5	nM	CHEMBL5575484
8.22	IC50	6	nM	CHEMBL4446681
8.15	IC50	7	nM	CHEMBL5566424
8.05	IC50	8.91	nM	CHEMBL4793447
8.05	IC50	8.82	nM	CHEMBL4785886
8.02	IC50	9.56	nM	CHEMBL4777356
8.01	IC50	9.8	nM	CHEMBL4776812
8.00	Kd	10	nM	CHEMBL5179988
8.00	IC50	10	nM	CHEMBL5095897
7.96	IC50	11	nM	CHEMBL5179988
7.92	IC50	12	nM	CHEMBL4278808
7.92	IC50	12	nM	CHEMBL5188318
7.89	IC50	12.8	nM	CHEMBL4781993
7.87	IC50	13.6	nM	CHEMBL5561973
7.85	IC50	14	nM	CHEMBL4642838
7.85	IC50	14	nM	CHEMBL4278808
7.82	Kd	15	nM	CHEMBL4848254
7.80	IC50	15.9	nM	CHEMBL4785713
7.78	IC50	16.5	nM	CHEMBL5826420
7.76	IC50	17.5	nM	CHEMBL4797007
7.72	IC50	19	nM	STAUROSPORINE
7.65	IC50	22.4	nM	CHEMBL4779550
7.63	IC50	23.6	nM	CHEMBL6191865
7.62	IC50	24.2	nM	CHEMBL4789603
7.59	IC50	25.6	nM	CHEMBL4795368
7.58	IC50	26.6	nM	CHEMBL6022963
7.58	IC50	26.2	nM	CHEMBL4789125
7.56	IC50	27.6	nM	CHEMBL4780792
7.55	IC50	28	nM	CHEMBL6173699
7.51	IC50	30.6	nM	CHEMBL6191307
7.50	IC50	32	nM	STAUROSPORINE
7.50	IC50	32	nM	CHEMBL5187817
7.50	IC50	31.8	nM	CHEMBL4789863
7.50	IC50	31.7	nM	CHEMBL6191783
7.47	IC50	34	nM	SGI-1776

PubChem BioAssay actives

162 with measured affinity, of 936 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
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-6-azaniumyl-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-(diaminomethylideneazaniumyl)-1-oxopentan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-azaniumylpropanoyl]amino]-5-(diaminomethylideneazaniumyl)pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802698: Equilibrium Binding/Displacement Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	<0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-6-[[(3R)-3-[6-[[(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-3-carboxypropanoyl]amino]-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-[[(2S,3S)-1-[[(2S)-1-[[(2R)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1846289: Binding affinity to haspin (unknown origin) assessed as dissociation constant	kd	<0.0001	uM
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-6-[[3-carboxy-4-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoyl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[amino(azaniumylidene)methyl]amino]-1-oxopentan-2-yl]amino]-5-[[(2S)-5-[[amino(azaniumylidene)methyl]amino]-2-[[(2S)-2-azaniumylpropanoyl]amino]pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802698: Equilibrium Binding/Displacement Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	0.0001	uM
(2R,3R,4S,5R)-2-(4-amino-5-ethynylpyrrolo[2,3-d]pyrimidin-7-yl)-5-(azidomethyl)thiolane-3,4-diol	2110489: Inhibition of recombinant human N-terminal GST-tagged haspin (470 to end residues) expressed in baculovirus infected Sf9 cells using histone H3 peptide as substrate by ADP-Glo kinase assay	ic50	0.0002	uM
3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine	2003942: Inhibition of haspin (unknown origin) assessed as dissociation constant	kd	0.0002	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-[[(3R)-4-amino-3-[6-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoyl]amino]-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-N-[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]pentanediamide	1846303: Binding affinity to N-terminal his6-tagged human recombinant Haspin (470 to 798 residues) assessed as dissociation constant	kd	0.0004	uM
N-[(5-methyl-1H-imidazol-2-yl)methyl]-4-(8,9,10,11-tetrahydro-3H-pyrazolo[4,5-a]phenanthridin-7-yl)benzamide	2003942: Inhibition of haspin (unknown origin) assessed as dissociation constant	kd	0.0006	uM
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-6-[[3-carboxy-4-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoyl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[amino(azaniumylidene)methyl]amino]-1-oxopentan-2-yl]amino]-5-[[(2S)-5-[[amino(azaniumylidene)methyl]amino]-2-[[(2S)-2-azaniumylpropanoyl]amino]pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802699: Kinetic Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	0.0028	uM
1-[5-(2,4-difluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0030	uM
10-nitropyrido[3,4-g]quinolin-2-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0030	uM
N-[[4-(aminomethyl)phenyl]methyl]-3-[[(4-hydroxyphenyl)methyl-methylamino]methyl]-1-methylindole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0030	uM
N-(4-morpholin-4-ylcyclohexyl)-5-(oxan-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1471973: Inhibition of recombinant N-terminal His6-tagged human haspin (471 end residues) expressed in baculovirus infected Sf21 insect cells	ic50	0.0040	uM
(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carboxylic acid	1846305: Binding affinity to a TEV-cleavable N-terminal His6-tagged human recombinant haspin (470 to 798 residues) assessed as dissociation constant	kd	0.0040	uM
N-(4-fluorophenyl)-3-[[(3-hydroxyphenyl)methyl-methylamino]methyl]-1-methylindole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0050	uM
4-N-[5-(6-methoxy-3-pyridinyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]cyclohexane-1,4-diamine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0050	uM
(2R,3R,4S,5R)-2-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol	2110487: Inhibition of haspin (unknown origin)	ic50	0.0050	uM
N-(4-fluorophenyl)-1-methyl-3-[[methyl-[2-(4-phenylphenyl)ethyl]amino]methyl]indole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0060	uM
3-[(benzylamino)methyl]-N-(4-fluorophenyl)-1-methylindole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0070	uM
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2R)-1-amino-6-[[3-carboxy-4-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-6-(tetradecanoylamino)hexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[amino(azaniumylidene)methyl]amino]-1-oxopentan-2-yl]amino]-5-[[(2S)-5-[[amino(azaniumylidene)methyl]amino]-2-[[(2S)-2-azaniumylpropanoyl]amino]pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802698: Equilibrium Binding/Displacement Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	0.0084	uM
1-N-[5-(2,4-difluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-methylpropane-1,2-diamine	1903482: Binding affinity to human HASPIN	kd	0.0100	uM
3-(2,7-dimethoxyacridin-9-yl)sulfanylpropan-1-amine	2110487: Inhibition of haspin (unknown origin)	ic50	0.0100	uM
3-fluoro-4-(8,9,10,11-tetrahydro-3H-pyrazolo[4,5-a]phenanthridin-7-yl)phenol	1417230: Inhibition of Haspin (unknown origin) after 3 hrs by ADP-Glo assay	ic50	0.0120	uM
2-methylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0120	uM
5,6-dibromo-4-(difluoromethyl)-1-(oxan-4-yl)-2-piperazin-1-ylbenzimidazole	2070988: Inhibition of HASPIN (unknown origin) by ADP-Glo assay	ic50	0.0136	uM
(2Z)-6-hydroxy-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-1-benzofuran-3-one	1659938: Inhibition of human recombinant Haspin (470 to 798 residues) expressed in bacteria using Histone H3 and ARTKQTARKSTGGKAPRKQLA as substrate in presence of ATP incubated for 50 mins by ADP-GloTM assay	ic50	0.0140	uM
N,N-dimethyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1752098: Binding affinity to wild-type human partial length HASPIN (I452 to K798 residues) expressed in mammalian expression system measured after 1 hr by competitive binding assay	kd	0.0150	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	1612688: Inhibition of human haspin using Histone H3 as substrate by [gamma-33P]-ATP assay	ic50	0.0190	uM
1-methyl-3-pyridin-4-ylpyrrolo[3,2-g]isoquinoline	2277555: Inhibition of recombinant human haspin kinase domain (470 to 798 residues) extracted from bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0236	uM
2-hydroxy-8-methoxyindeno[2,1-b][1]benzothiol-6-one	2258625: Inhibition of GSG2 (haspin) (unknown origin) by Adapta kinase activity assay relative to control	ic50	0.0280	uM
3-pyridin-3-yl-1H-pyrrolo[3,2-g]isoquinoline	2277555: Inhibition of recombinant human haspin kinase domain (470 to 798 residues) extracted from bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0306	uM
1-methyl-3-pyridin-3-ylpyrrolo[3,2-g]isoquinoline	2277555: Inhibition of recombinant human haspin kinase domain (470 to 798 residues) extracted from bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0317	uM
1-[5-(2-fluoro-4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0320	uM
N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine	706708: Inhibition of haspin	ic50	0.0340	uM
2-(4-fluorophenyl)-N-[5-(4-pyridin-3-ylthiophen-2-yl)-3-pyridinyl]acetamide	1417224: Inhibition of recombinant human Haspin expressed in Baculovirus expression system by Adapta assay	ic50	0.0360	uM
2-methyl-6-pyridin-4-yl-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazine	2075065: Binding affinity to biotinylated super-streptavidin biosensor immobilised Haspin (unknown origin) assessed as dissociation constant by biolayer interferometry	kd	0.0393	uM
1-[5-(cyclohexen-1-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0450	uM
6,7-dibromo-5-methyl-2-piperazin-1-yl-1,3-diazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene	2070988: Inhibition of HASPIN (unknown origin) by ADP-Glo assay	ic50	0.0460	uM
2-methoxy-10-nitropyrido[3,4-g]quinazoline	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0500	uM
2-propan-2-ylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0560	uM
1-ethylpyrazolo[5,4-g]isoquinolin-9-amine	2107092: Inhibition of recombinant human Haspin kinase domain (470 to 798 residues) expressed in bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0620	uM
2-propylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0650	uM
N-(4-fluorophenyl)-1-methyl-3-[(naphthalen-1-ylmethylamino)methyl]indole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0650	uM
2-butylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0690	uM
1H-pyrrolo[3,2-g]isoquinoline-3-carbonitrile	2107092: Inhibition of recombinant human Haspin kinase domain (470 to 798 residues) expressed in bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0750	uM
3-pyridin-4-yl-1H-pyrrolo[3,2-g]isoquinoline	2107092: Inhibition of recombinant human Haspin kinase domain (470 to 798 residues) expressed in bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0760	uM
N-[5-(4-pyridin-3-ylthiophen-2-yl)-3-pyridinyl]cyclopropanecarboxamide	1408874: Inhibition of human GST-tagged haspin expressed in baculovirus expression system in presence of 100 uM ATP	ic50	0.0763	uM
(2E)-6-hydroxy-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-3,4-dihydronaphthalen-1-one	1659938: Inhibition of human recombinant Haspin (470 to 798 residues) expressed in bacteria using Histone H3 and ARTKQTARKSTGGKAPRKQLA as substrate in presence of ATP incubated for 50 mins by ADP-GloTM assay	ic50	0.0770	uM
1-[5-(6-methoxy-2-pyridinyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0780	uM
3-pyridin-2-yl-1H-pyrrolo[3,2-g]isoquinoline	2277555: Inhibition of recombinant human haspin kinase domain (470 to 798 residues) extracted from bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0844	uM
8-[[6-(2-methoxyethylcarbamoyl)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474316: Binding affinity to partial length wild-type human HASPIN (I452 to K798 residues) expressed in bacterial expression system by kinome scan assay	kd	0.0860	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
chromium hexavalent ion	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Demecolcine	decreases expression	1
Oxygen	decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

280 unique, capped per target: 273 binding, 5 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1067026	Binding	Inhibition of human haspin at 0.1 uM	Identification of potent and selective VEGFR receptor tyrosine kinase inhibitors having new amide isostere headgroups. — *Bioorg Med Chem Lett*
CHEMBL4275974	ADMET	Inhibition of human GST-tagged haspin expressed in baculovirus expression system at 1.25 uM in presence of 100 uM ATP relative to control	Development of novel amide-derivatized 2,4-bispyridyl thiophenes as highly potent and selective Dyrk1A inhibitors. Part II: Identification of the cyclopropylamide moiety as a key modification. — *Eur J Med Chem*
CHEMBL5160033	Toxicity	Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SQ63	HAP1 GSG2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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