PLK2

Summary

PLK2 (polo like kinase 2, HGNC:19699) is a protein-coding gene on chromosome 5q11.2, encoding Serine/threonine-protein kinase PLK2 (Q9NYY3). Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition.

The protein encoded by this gene is a member of the polo family of serine/threonine protein kinases that have a role in normal cell division. This gene is most abundantly expressed in testis, spleen and fetal tissues, and its expression is inducible by serum, suggesting that it may also play an important role in cells undergoing rapid cell division. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10769 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 51 total
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 12 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_006622
• Interaction hub: 1,783 STRING partners (top 10% of genes corpus-wide)
• Notable: 51 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19699
Approved symbol	PLK2
Name	polo like kinase 2
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SNK
Ensembl gene	ENSG00000145632
Ensembl biotype	protein_coding
OMIM	607023
Entrez	10769

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 12 retained_intron, 7 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000274289

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 9, TSL 3: 1, TSL 4: 1, TSL 5: 3

ENST00000274289, ENST00000502671, ENST00000503115, ENST00000503378, ENST00000503713, ENST00000504196, ENST00000505244, ENST00000508300, ENST00000509422, ENST00000509555, ENST00000510629, ENST00000511326, ENST00000514306, ENST00000515415, ENST00000617412, ENST00000862409, ENST00000932191, ENST00000971658, ENST00000971659, ENST00000992000, ENST00001045027, ENST00001135554

RefSeq mRNA: 2 — MANE Select: NM_006622 NM_001252226, NM_006622

CCDS: CCDS3974, CCDS75250

Canonical transcript exons

ENST00000274289 — 14 exons

Exon	Start	End
ENSE00001001081	58459690	58460086
ENSE00001592709	58453982	58454774
ENSE00001599141	58454911	58455021
ENSE00001739399	58456026	58456155
ENSE00003466000	58457488	58457583
ENSE00003509338	58458084	58458171
ENSE00003538270	58455285	58455414
ENSE00003568624	58458399	58458528
ENSE00003591624	58458725	58458841
ENSE00003602138	58456492	58456589
ENSE00003602624	58456945	58457092
ENSE00003618806	58457181	58457379
ENSE00003642809	58458985	58459092
ENSE00003682361	58455539	58455779

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.7533 / max 873.6556, expressed in 1648 samples.

Highest expression (Bgee): spleen, apex of heart, cortical plate, endometrium epithelium, endocervix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.8e-10	+0.25	5:58460156:T:C
Cells Cultured fibroblasts	eqtl	5.6e-05	-0.17	5:57460181:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.2e-04	-0.23	5:58471095:C:G
Colon Transverse	eqtl	1.6e-03	-0.24	5:59220231:TA:T
Nerve Tibial	eqtl	3.4e-03	+0.22	5:58426914:G:A
Brain Anterior cingulate cortex BA24	eqtl	3.9e-03	+0.57	5:59281171:G:A
Adipose Subcutaneous	eqtl	4.4e-03	-0.14	5:58304724:T:C
Skin Sun Exposed Lower leg	eqtl	6.8e-03	+0.16	5:58182491:A:G
Brain Caudate basal ganglia	eqtl	9.3e-03	+0.12	5:58016327:A:G
Brain Putamen basal ganglia	eqtl	1.3e-02	-0.16	5:59141700:G:A
Brain Frontal Cortex BA9	eqtl	2.5e-02	+0.15	5:58025049:GT:G
Muscle Skeletal	eqtl	4.3e-02	+0.45	5:57506572:A:ATCTATCTATCT

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
61777	80.5813	1647
61775	0.6160	275
61774	0.5094	265
61776	0.0466	13

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	98.28	gold quality
apex of heart	UBERON:0002098	97.29	gold quality
cortical plate	UBERON:0005343	97.28	gold quality
endometrium epithelium	UBERON:0004811	97.25	gold quality
endocervix	UBERON:0000458	97.16	gold quality
ectocervix	UBERON:0012249	97.07	gold quality
islet of Langerhans	UBERON:0000006	96.93	gold quality
colonic epithelium	UBERON:0000397	96.86	gold quality
skin of abdomen	UBERON:0001416	96.86	gold quality
adrenal tissue	UBERON:0018303	96.85	gold quality
calcaneal tendon	UBERON:0003701	96.83	gold quality
gall bladder	UBERON:0002110	96.61	gold quality
tibial nerve	UBERON:0001323	96.36	gold quality
skin of leg	UBERON:0001511	96.01	gold quality
penis	UBERON:0000989	95.74	gold quality
mammary duct	UBERON:0001765	95.62	gold quality
primary visual cortex	UBERON:0002436	95.58	gold quality
zone of skin	UBERON:0000014	95.45	gold quality
nucleus accumbens	UBERON:0001882	95.37	gold quality
esophagus mucosa	UBERON:0002469	95.35	gold quality
epithelium of mammary gland	UBERON:0003244	95.35	gold quality
tongue squamous epithelium	UBERON:0006919	95.32	gold quality
body of uterus	UBERON:0009853	95.13	gold quality
dorsal root ganglion	UBERON:0000044	95.10	gold quality
middle temporal gyrus	UBERON:0002771	95.06	gold quality
thoracic mammary gland	UBERON:0005200	95.06	gold quality
mammary gland	UBERON:0001911	95.00	gold quality
upper lobe of left lung	UBERON:0008952	94.99	gold quality
smooth muscle tissue	UBERON:0001135	94.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.97	gold quality
left uterine tube	UBERON:0001303	94.91	gold quality
caudate nucleus	UBERON:0001873	94.87	gold quality
putamen	UBERON:0001874	94.77	gold quality
uterine cervix	UBERON:0000002	94.72	gold quality
prefrontal cortex	UBERON:0000451	94.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.70	gold quality
sural nerve	UBERON:0015488	94.58	gold quality
trigeminal ganglion	UBERON:0001675	94.45	gold quality
upper lobe of lung	UBERON:0008948	94.45	gold quality
occipital lobe	UBERON:0002021	94.44	gold quality
right frontal lobe	UBERON:0002810	94.42	gold quality
right lung	UBERON:0002167	94.29	gold quality
frontal cortex	UBERON:0001870	94.24	gold quality
upper leg skin	UBERON:0004262	94.22	gold quality
right ovary	UBERON:0002118	94.01	gold quality
visceral pleura	UBERON:0002401	94.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.91	gold quality
frontal pole	UBERON:0002795	93.87	gold quality
neocortex	UBERON:0001950	93.84	gold quality
heart left ventricle	UBERON:0002084	93.71	gold quality
left ovary	UBERON:0002119	93.70	gold quality
cardiac ventricle	UBERON:0002082	93.64	gold quality
right atrium auricular region	UBERON:0006631	93.62	gold quality
CA1 field of hippocampus	UBERON:0003881	93.56	gold quality
cerebral cortex	UBERON:0000956	93.53	gold quality
adult organism	UBERON:0007023	93.50	gold quality
cardiac atrium	UBERON:0002081	93.46	gold quality
vagina	UBERON:0000996	93.38	gold quality
heart	UBERON:0000948	93.26	gold quality
telencephalon	UBERON:0001893	93.20	gold quality
descending thoracic aorta	UBERON:0002345	92.97	gold quality
parietal pleura	UBERON:0002400	92.97	gold quality
pancreas	UBERON:0001264	92.92	gold quality
pleura	UBERON:0000977	92.84	gold quality
palpebral conjunctiva	UBERON:0001812	92.77	gold quality
gingival epithelium	UBERON:0001949	92.76	gold quality
thoracic aorta	UBERON:0001515	92.74	gold quality
ovary	UBERON:0000992	92.66	gold quality
cingulate cortex	UBERON:0003027	92.62	gold quality
ascending aorta	UBERON:0001496	92.60	gold quality
orbitofrontal cortex	UBERON:0004167	92.59	gold quality
anterior cingulate cortex	UBERON:0009835	92.57	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.45	gold quality
superior frontal gyrus	UBERON:0002661	92.32	gold quality
right lobe of liver	UBERON:0001114	92.28	gold quality
gingiva	UBERON:0001828	92.22	gold quality
lower esophagus mucosa	UBERON:0035834	92.20	gold quality
saliva-secreting gland	UBERON:0001044	92.17	gold quality
minor salivary gland	UBERON:0001830	92.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.10	gold quality
mouth mucosa	UBERON:0003729	92.02	gold quality
skin of hip	UBERON:0001554	91.97	gold quality
Ammon’s horn	UBERON:0001954	91.93	gold quality
ganglionic eminence	UBERON:0004023	91.87	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.84	gold quality
amniotic fluid	UBERON:0000173	91.81	gold quality
squamous epithelium	UBERON:0006914	91.70	gold quality
left lobe of thyroid gland	UBERON:0001120	91.69	gold quality
myocardium	UBERON:0002349	91.69	gold quality
esophagus	UBERON:0001043	91.66	gold quality
lung	UBERON:0002048	91.66	gold quality
omental fat pad	UBERON:0010414	91.55	gold quality
forebrain	UBERON:0001890	91.54	gold quality
peritoneum	UBERON:0002358	91.53	gold quality
trachea	UBERON:0003126	91.48	gold quality
left testis	UBERON:0004533	91.45	gold quality
myometrium	UBERON:0001296	91.30	gold quality
testis	UBERON:0000473	91.24	gold quality
body of pancreas	UBERON:0001150	91.21	gold quality
thyroid gland	UBERON:0002046	91.20	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	1230.77
E-MTAB-7008	yes	672.98
E-MTAB-6701	yes	75.35
E-HCAD-10	yes	33.98
E-MTAB-8271	yes	15.95
E-HCAD-5	yes	13.99
E-CURD-112	yes	7.88
E-GEOD-84465	yes	6.30
E-MTAB-9689	no	794.06
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	190.3
Hippocampal formation	tissue	155.7
Frontal cortex	tissue	125.9
Putamen	tissue	111.0
Cerebral cortex	tissue	96.9	high
Occipital cortex	tissue	96.9
Somatosensory cortex	tissue	96.4
Prefrontal cortex	tissue	91.9
Spinal cord	tissue	87.0
Retrosplenial and cingulate cortex	tissue	86.1
Entorhinal cortex	tissue	83.4
Temporal cortex	tissue	80.6
Motor cortex	tissue	79.7
Retrosplenial cortex	tissue	78.2
Basal ganglia	tissue	77.5	medium
Spleen	tissue	70.2	medium
Insular cortex	tissue	70.0
Nucleus accumbens	tissue	62.1
Amygdala	tissue	51.9
Heart muscle	tissue	51.2	medium
Hippocampus	tissue	49.8	medium
Ventral forebrain	tissue	46.7
Postcentral gyrus	tissue	45.1
Placenta	tissue	44.8	high
Salivary gland	tissue	40.5	high
Breast	tissue	38.0	high
Testis	tissue	35.7	high
Vagina	tissue	32.9	medium
Cervix	tissue	31.8	high
Septum	tissue	31.2
Lung	tissue	30.4	high
Gallbladder	tissue	30.1	high
Liver	tissue	29.1	medium
Choroid plexus	tissue	29.0
Skin 1	tissue	28.4	medium
Urinary bladder	tissue	27.8	high
Endometrium 1	tissue	27.2	medium
Thalamus	tissue	26.6
Superior colliculi	tissue	26.5
Esophagus	tissue	25.8	medium
Smooth muscle	tissue	24.8	high
Olfactory bulb	tissue	24.8
Pancreas	tissue	22.1	high
Midbrain	tissue	20.3
Pons	tissue	18.7
Ovary	tissue	18.3	medium
Hypothalamus	tissue	14.2
Adipose tissue	tissue	13.9	low
Rectum	tissue	13.7	high
Medulla oblongata	tissue	13.4
Substantia nigra	tissue	13.4
Tongue	tissue	12.7
Fallopian tube	tissue	12.4	medium
Thyroid gland	tissue	11.4	high
Prostate	tissue	10.4	high
Corpus callosum	tissue	10.1
Seminal vesicle	tissue	9.8	high
Colon	tissue	9.5	high
Epididymis	tissue	8.8	medium
Bone marrow	tissue	8.8	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal hippocampus (155.7), Ventral hippocampus (135.5), Subiculum (107.3), Hippocampus, CA1 (89.5), Dorsal spinal cord (87.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESRRG, GATA1, TP53

miRNA regulators (miRDB)

Targeting PLK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 61 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-505-3P	99.19	69.71	896

Functional genomics

gnomAD constraint: pLI 0.996, LOEUF 0.471, missense Z 3.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000274289 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈3% 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
5:58,454,586–58,455,596	130 / 196.4	0.66	no
5:58,455,597–58,455,658	1 / 23.1	0.04	yes (p 4.2e-06)
5:58,455,659–58,456,971	129 / 156.0	0.83	no
5:58,456,972–58,459,690	179 / 342.3	0.52	no
5:58,459,691–58,459,959	127 / 122.5	1.04	no

Literature-anchored findings (GeneRIF, showing 40)

• there is a mitotic checkpoint wherein p53-dependent activation of Snk/Plk2 prevents mitotic catastrophe following spindle damage (PMID:12897130)
• hVPS18 may play an important role in regulation of SNK activity through its ubiquitin ligase (PMID:16203730)
• Calcipotriol affects proliferation of keratinocytes by decreasing the expression of EGR1 and PLK2 (PMID:17671831)
• increased cell death observed after aphidicolin treatment and release in Plk2-deficient cells may result from both higher levels of replication stress-induced DNA damage and a dysfunctional S-phase checkpoint (PMID:17912033)
• Plk2 mediated centriole duplication is dependent on Plk4 function (PMID:19001868)
• PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay (PMID:19004816)
• overexpression of PLK2 in bladder carcinomas, suggesting a possible role of PLK2 in the pathogenesis of bladder carcinomas (PMID:19506885)
• Data show that PLK2 as a kinase that phosphorylates Ser-137 of PLK1, which is sufficient to mediate this survival signal. (PMID:19706541)
• Our results point to a novel Plk2-TSC1 interaction with effects on mTOR signaling during hypoxia, and tumor growth that may enable targeting Plk2 signaling in cancer therapy. (PMID:20054236)
• NPM/B23 is a direct target of Plk2 in the regulation of centriole duplication and that phosphorylation on serine 4 can trigger this process (PMID:20352051)
• Results identify centrosomal P4.1-associated protein (CPAP), a human homologue of SAS-4, as a substrate of PLK2 whose activity oscillates during the cell cycle. (PMID:20531387)
• Identification of Snk/Plk2 as a novel methylated gene in multiple myeloma. (PMID:21067440)
• Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes. (PMID:21340720)
• Results implicate Plk2 as a clinically important determinant of chemosensitivity. (PMID:21402713)
• phosphorylation sites could play an important role in the rapid activation, expansion, and prolongation of Plk2 signaling (PMID:22100274)
• Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop. (PMID:22134238)
• Acetylation of GATA-1 responsive elements in Polo-like kinase 2 plays a crucial role in Plk2 transcription and protein expression in MG-63 cells. (PMID:22138223)
• PLK2 and to a lesser extent PLK3 are superior over CK2, as catalysts of Ser-129 phosphorylation both in full length alpha-synuclein and in a peptide reproducing the C-terminal segment of the protein. (PMID:22248692)
• The methylation status of the PLK2 CpG island predicts outcomes in patients treated with carboplatin and paclitaxel chemotherapy. (PMID:22289679)
• Phosphorylation of Fbxw7 by Plk2 induces destabilization of the F-box protein resulting in accumulation of cyclin E and increased potential for centriole reproduction (PMID:22399798)
• have identified and validated as in vitro PLK2 and PLK3 substrates HSP90, GRP-94, beta-tubulin, calumenin, and 14-3-3 epsilon (PMID:22828320)
• PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. (PMID:23466428)
• This study supports a role for PLK2 in the generation of aSyn inclusions by a mechanism that does not depend directly on serine 129 phosphorylation. (PMID:23677647)
• Polo-like kinase 2 is a mediator of hedgehog survival signaling in cholangiocarcinoma. (PMID:23703673)
• Our findings suggest a new role for PLK2 in the regulation of inflammatory diseases by modulating ADAM17 activity. (PMID:24338472)
• PLK2 SNPs were associated with Alzheimer disease and mild cognitive impairment. PLK2-rs15009 CC and GG genotypes and CC genotype at PLK2-rs702723 were protective for AD. (PMID:24384746)
• the regulation of redox homeostasis by PLK2 promotes the survival of cells with dysfunctional mitochondria (PMID:24887096)
• Study indicates that miR-126 is a tumor suppressor that inhibits gastric cancer cells proliferation by targeting PI3KR2, Crk and PLK2. (PMID:24969300)
• Data shows that PLK2 mRNA is a direct target of miR-27a in laryngeal squamous cell carcinoma. (PMID:25239093)
• Unique PLK2-dependent protein phosphorylation sites identified by mass spectrometry. (PMID:25338102)
• Decreased PLK2 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies. (PMID:25347426)
• Silencing of polo-like kinase 2 increases cell proliferation and decreases apoptosis in SGC-7901 gastric cancer cells. (PMID:25501818)
• this study reports the first crystal structure of the C-terminal polo-box domain of PLK2. (PMID:25511705)
• PLK2 indirectly activates ROCK2 via phosphorylating nucleophosmin during centrosome amplification. (PMID:25590559)
• Structural analysis of the polo-box domain of human PLK2 has been presented. (PMID:25846005)
• these findings reveal a conserved PLK2-RAP1 pathway that is crucial to regulate endothelial tip cell behavior in order to ensure proper vascular development and patterning in vertebrates. (PMID:26004360)
• Data suggest wild-type SNCA (alpha-synuclein) binding to synaptosome membrane is not affected by phosphorylation by PLK2; A30P SNCA, a Parkinson disease mutation, binding is greatly increased; endocytosis of SNCA fibrils follows similar pattern. (PMID:26719332)
• Findings indicate the interaction network of viral oncogene HPV16 E7, miR-27b and PLK2, and support the potential strategies using antisense nucleic acid of miR-27b for therapy of cervical cancer. (PMID:26910911)
• Plk2 represents an independent prognostic marker and regulates tumor growth and apoptosis by targeting Fbxw7/Cyclin E pathway in colorectal carcinoma. (PMID:27423313)
• PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes i (PMID:27579920)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plk2b	ENSDARG00000019130
danio_rerio	plk2a	ENSDARG00000090752
mus_musculus	Plk2	ENSMUSG00000021701
rattus_norvegicus	Plk2	ENSRNOG00000011951

Paralogs (4): PLK4 (ENSG00000142731), PLK1 (ENSG00000166851), PLK3 (ENSG00000173846), PLK5 (ENSG00000185988)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1099790) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
delayed bone ossification	1
decreased body size	1
eyelids open at birth	1
abnormal placenta development	1
abnormal placenta labyrinth morphology	1
abnormal cell cycle	1
pallor	1
embryonic growth retardation	1
decreased placenta weight	1
decreased fetal weight	1
preweaning lethality, complete penetrance	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
Drosophila persimilis	B4HBU3	99.9%	Diamond
Drosophila pseudoobscura pseudoobscura	Q2LYK3	99.9%	Diamond
Pongo abelii	Q5R4L1	99.9%	Diamond
Drosophila sechellia	B4IAQ8	99.0%	Diamond
Drosophila simulans	B4QK53	99.0%	Diamond
Drosophila melanogaster	O97143	98.3%	Diamond
Xenopus tropicalis	P62205	96.5%	Diamond
Xenopus laevis	P70032	96.5%	Diamond
Drosophila erecta	B3NE99	96.1%	Diamond
Drosophila yakuba	B4PDM5	96.1%	Diamond
Bos taurus	Q2TA25	95.7%	Diamond
Macaca fascicularis	Q8WNU8	95.1%	Diamond
Drosophila virilis	B4LDJ6	85.6%	Diamond
Drosophila mojavensis	B4KYX8	85.4%	Diamond
Drosophila grimshawi	B4J3F1	83.3%	Diamond
Drosophila ananassae	B3M6I4	82.9%	Diamond
Corynebacterium efficiens YS-314	Q8FUI4	76.1%	Diamond
Oryza sativa Japonica Group	Q94CU5	74.2%	Diamond
Culex quinquefasciatus	B0WAU8	74.0%	Diamond
Aedes aegypti	Q16W24	74.0%	Diamond
Arabidopsis thaliana	Q9SLI2	73.3%	Diamond
Caenorhabditis elegans	P34331	72.1%	Diamond
Drosophila willistoni	B4MXR8	69.6%	Diamond
Dictyostelium discoideum	Q75JN1	59.6%	Diamond
Caenorhabditis briggsae	Q621J7	57.5%	Diamond
Plasmodium falciparum 3D7	Q8I265	57.1%	Diamond
Plasmodium berghei ANKA	A0A509AH51	53.8%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SRL5	51.4%	Diamond
Saccharomyces cerevisiae S288C	P32562	48.3%	Diamond
Schizosaccharomyces pombe 972h-	P50528	47.5%	Diamond
Zea mays	P0C8M8	46.7%	Diamond
Candida albicans SC5314	Q5AP97	45.1%	Diamond
Nematostella vectensis	A7SNN5	42.1%	Diamond
Bovine herpesvirus type 1.2 strain st	Q08097	48.1%	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
LINC02108	ncRNA	101928600
RAB3C	protein-coding	115827
GAPT	protein-coding	202309
LINC02101	ncRNA	101928569
MIR548AE2	ncRNA	100616339

Protein

Protein identifiers

Serine/threonine-protein kinase PLK2 — Q9NYY3 (reviewed: Q9NYY3)

Alternative names: Polo-like kinase 2, Serine/threonine-protein kinase SNK, Serum-inducible kinase

All UniProt accessions (2): A0A087WUH9, Q9NYY3

UniProt curated annotations — full annotation on UniProt →

Function. Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CPAP, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CPAP and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.

Subunit / interactions. Interacts with NSF; causing NSF dissociation from GRIA2. Interacts with CIB1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cell projection. Dendrite.

Tissue specificity. Expressed at higher level in the fetal lung, kidney, spleen and heart.

Post-translational modifications. Catalytic activity is enhanced by phosphorylation of Thr-239.

Activity regulation. Activated by phosphorylation of Thr-239. Once activated, activity is stimulated by binding target proteins.

Domain organisation. The POLO box domains act as phosphopeptide-binding module that recognizes and binds serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK2 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them.

Induction. Directly regulated by p53/TP53. Negatively regulated by miR-126.

Miscellaneous. There are indications that PLK2 might act as a tumor suppressor: PLK2 is significantly down-regulated in a wide range of acute myeloid leukemias (AMLs) and B-cell lymphomas due to aberrant cytosine methylation in the CpG island located at the 5’ of the PLK2 gene. Moreover, miR-126, a microRNA that negatively regulates PLK2 is up-regulated in AMLs, suggesting that PLK2 down-regulation by miR-126 could also contribute to leukemogenesis.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NYY3-1	1	yes
Q9NYY3-2	2

RefSeq proteins (2): NP_001239155, NP_006613* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000959	POLO_box_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR033695	POLO_box_2	Domain
IPR033701	POLO_box_1	Domain
IPR036947	POLO_box_dom_sf	Homologous_superfamily
IPR042825	PLK2_STKc	Domain

Pfam: PF00069, PF00659

Enzyme classification (BRENDA)

• EC 2.7.11.21 — polo kinase (BRENDA: 16 organisms, 193 substrates, 436 inhibitors, 20 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0002–0.0076	13
CDC25C	0.0006–0.0008	6
CASEIN	0.0014	1

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 (67 total): helix 22, strand 19, turn 5, sequence variant 4, mutagenesis site 4, domain 3, region of interest 2, binding site 2, chain 1, modified residue 1, splice variant 1, sequence conflict 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
4I5P	Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein …	X-RAY DIFFRACTION	1.74
4I6B	Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein …	X-RAY DIFFRACTION	1.8
4I5M	Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein …	X-RAY DIFFRACTION	1.8
4I6H	Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce …	X-RAY DIFFRACTION	1.91
4RS6	Crystal structure of the C domain of Polo like Kinase II in Homo Sapiens	X-RAY DIFFRACTION	2.6
4XB0	Structure of the Plk2 polo-box domain	X-RAY DIFFRACTION	2.7
4I6F	Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein …	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYY3-F1	76.64	0.47

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; mitochondria; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

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
205	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
88–96	ATP
111	ATP

Post-translational modifications (1)

Type	Positions
Phosphothreonine	239

Mutagenesis-validated functional residues (4)

Position	Phenotype
210	loss of kinase activity.
503	impairs localization to the centrosome and centriole duplication; when associated with a-629 and m-631.
629	impairs localization to the centrosome and centriole duplication; when associated with f-503 and m-631.
631	impairs localization to the centrosome and centriole duplication; when associated with f-503 and a-631.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 15; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

15 pathways:

ID	Pathway	Evidence
R-HSA-9662834	CD163 mediating an anti-inflammatory response ⚕	curated
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	curated
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664433	Leishmania parasite growth and survival ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9768919	NPAS4 regulates expression of target genes	electronic
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes	—
R-HSA-9634815	Transcriptional Regulation by NPAS4	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 452 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_MEMORY, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, BOYLAN_MULTIPLE_MYELOMA_PCA1_DN, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_INFLAMMATORY_RESPONSE, DORN_ADENOVIRUS_INFECTION_12HR_UP

GO Biological Process (21): G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), protein phosphorylation (GO:0006468), mitotic spindle organization (GO:0007052), Ras protein signal transduction (GO:0007265), memory (GO:0007613), positive regulation of autophagy (GO:0010508), negative regulation of angiogenesis (GO:0016525), DNA damage response, signal transduction by p53 class mediator (GO:0030330), Rap protein signal transduction (GO:0032486), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of protein catabolic process (GO:0045732), regulation of centriole replication (GO:0046599), regulation of synaptic plasticity (GO:0048167), long-term synaptic potentiation (GO:0060291), long-term synaptic depression (GO:0060292), negative regulation of apoptotic process in bone marrow cell (GO:0071866), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), negative regulation of cellular senescence (GO:2000773), regulation of cell cycle process (GO:0010564)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), ATP-dependent protein binding (GO:0043008), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): kinetochore (GO:0000776), chromatin (GO:0000785), spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), dendrite (GO:0030425)

Reactome top-level categories

12 top-level categories:

Category	Pathways
Generic Transcription Pathway	2
TP53 Regulates Transcription of Cell Cycle Genes	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Transcriptional Regulation by NPAS4	1
RNA Polymerase II Transcription	1
Disease	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1
Parasitic Infection Pathways	1
Leishmania parasite growth and survival	1
Leishmania infection	1
Infectious disease	1

GO top-level categories

showing 60 of 73 GO namespaces:

Category	Terms
cellular anatomical structure	4
mitotic cell cycle	2
small GTPase-mediated signal transduction	2
positive regulation of catabolic process	2
regulation of synaptic plasticity	2
protein kinase activity	2
intracellular membraneless organelle	2
microtubule organizing center	2
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
phosphorylation	1
protein modification process	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
learning or memory	1
autophagy	1
regulation of autophagy	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
centriole replication	1
regulation of centrosome duplication	1
regulation of organelle assembly	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
positive regulation of synaptic transmission	1
negative regulation of synaptic transmission	1
negative regulation of apoptotic process	1
apoptotic process in bone marrow cell	1
regulation of apoptotic process in bone marrow cell	1
cell migration involved in sprouting angiogenesis	1
positive regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
negative regulation of cellular process	1
cellular senescence	1
regulation of cellular senescence	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 39 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
G1/S transition of mitotic cell cycle	BP	mutant phenotype
mitotic spindle organization	BP	direct assay
positive regulation of autophagy	BP	direct assay
positive regulation of protein catabolic process	BP	direct assay
protein phosphorylation	BP	direct assay
regulation of centriole replication	BP	direct assay
centriole	CC	direct assay
centrosome	CC	direct assay
cytoplasm	CC	direct assay
ATP-dependent protein binding	MF	direct assay
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,783 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLK2	TP53	P04637	499
PLK2	CDC5L	Q99459	491
PLK2	SUN1	O94901	457
PLK2	SESN1	Q9Y6P5	416
PLK2	SPO11	Q9Y5K1	410
PLK2	SNCA	P37840	402
PLK2	CNTD1	Q8N815	398
PLK2	AEN	Q8WTP8	392
PLK2	TNPO3	Q9Y5L0	370
PLK2	ESPL1	Q14674	367
PLK2	CCNB1	P14635	366
PLK2	PHLDA3	Q9Y5J5	365
PLK2	VAMP4	O75379	363
PLK2	CCNA2	P20248	360
PLK2	BTG2	P78543	357

IntAct

Human interaction partners of PLK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
CDC20B	physical association	0.560	3
CPAP	phosphorylation reaction	0.440	3
PLK1	phosphorylation reaction	0.440	1
YWHAE	physical association	0.400	2
SFN	physical association	0.400	1
E2	physical association	0.370	4
CASK	physical association	0.370	1
E6	physical association	0.370	1
ANKRD28	association	0.350	2
C1orf226	association	0.350	1
H2AZ1	association	0.350	1
DLGAP4	physical association	0.000	1
ELP1	physical association	0.000	1
MPP3	physical association	0.000	1
NRIP1	physical association	0.000	1

BioGRID (112 interactions; top human partners by supporting records): NSF (Affinity Capture-MS; 5 records), ANKRD28 (Affinity Capture-MS; 3 records), ANKRD44 (Affinity Capture-MS; 3 records), CPA4 (Affinity Capture-MS; 3 records), CTSV (Affinity Capture-MS; 3 records), PAK2 (Affinity Capture-MS; 3 records), POF1B (Affinity Capture-MS; 3 records), RNASE7 (Affinity Capture-MS; 3 records), SDR9C7 (Affinity Capture-MS; 3 records), SERPINA12 (Affinity Capture-MS; 3 records), SERPINB7 (Affinity Capture-MS; 3 records), SNCA (Affinity Capture-Western; 3 records), SUGP1 (Affinity Capture-MS; 3 records), AP1B1 (Affinity Capture-MS; 2 records), AP2A1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 12 of 14 signaling interactions:

A	Effect	B	Mechanism
PLK2	up-regulates	NPM1	phosphorylation
PLK2	up-regulates	CENPJ	phosphorylation
PLK2	“down-regulates activity”	SNCA	phosphorylation
PLK2	“down-regulates activity”	SNCB	phosphorylation
PLK2	down-regulates	FBXW7	phosphorylation
VPS18	“down-regulates quantity by destabilization”	PLK2	ubiquitination
DYRK1A	“up-regulates quantity by stabilization”	PLK2	phosphorylation
PLK2	“down-regulates activity”	TP73	phosphorylation
PLK2	“up-regulates activity”	TP53	phosphorylation
PLK2	“up-regulates activity”	APP	phosphorylation
PLK2	“up-regulates activity”	LRPAP1	phosphorylation
PLK2	“up-regulates activity”	RAPGEF2	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for PLK2: 51 ClinVar records (0 pathogenic / likely pathogenic); 7 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 457):

Position(s)	Effect	Δscore	Sites
5:58454775–58454776	acceptor_gain	1.0000	2
5:58454909–58454910	donor_loss	1.0000	5
5:58454951	donor_gain	1.0000
5:58455022	acceptor_gain	1.0000
5:58455283–58455284	donor_loss	1.0000	4
5:58455415–58455416	acceptor_loss	1.0000	6
5:58455417	acceptor_gain	1.0000
5:58455425	acceptor_gain	1.0000
5:58455431	acceptor_gain	1.0000
5:58455675	donor_gain	1.0000

AlphaMissense

2,292 missense substitutions predicted likely pathogenic (of 4,550 scored), across 464 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
M579	9	0.995	1.000
M614	9	0.943	1.000
M584	9	0.913	0.995
M679	9	0.866	0.988
M217	9	0.861	0.992
F93	8	1.000	1.000
D205	8	1.000	1.000
N210	8	1.000	1.000
D223	8	1.000	1.000
D262	8	1.000	1.000
D509	8	1.000	1.000
H203	8	0.999	1.000
H629	8	0.999	1.000
H257	8	0.998	1.000
F280	8	0.998	1.000
N624	8	0.998	1.000
D151	8	0.997	1.000
F212	8	0.997	1.000
F516	8	0.997	1.000
F224	8	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:607023 | disease phenotypes:

GWAS associations

7 associations:

Study	Trait	p-value
GCST010244_363	Triglyceride levels	1e-12
GCST006627_47	Diastolic blood pressure	4e-12
GCST006988_109	Blond vs. brown/black hair color	4e-10
GCST012334_5	Multisite chronic pain	3e-8
GCST006530_2	Esophageal adenocarcinoma x smoking interaction	7e-7
GCST004125_16	Type 2 diabetes (age of onset)	4e-6
GCST008892_8	Working memory	5e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0006527	smoking status measurement
EFO:0006336	diastolic blood pressure
EFO:0003924	hair color
EFO:0004335	short-term memory
EFO:0004530	triglyceride measurement
EFO:0010100	multisite chronic pain

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5938 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 121,024 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

12 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL535	SUNITINIB	4	80,232
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL603469	LESTAURTINIB	3
CHEMBL1233528	VOLASERTIB	3	1,597
CHEMBL513909	BI-2536	2	932
CHEMBL1738758	ONVANSERTIB	2	828
CHEMBL475251	R-406	2	787
CHEMBL1672002	THYMOQUINONE	2	1,528
CHEMBL1908394	GSK-461364	1	1,158

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Polo-like kinase (PLK) family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
BI-2536	Inhibition	8.46	pIC50
rucaparib metabolite M324	Inhibition	6.23	pIC50
onvansertib	Inhibition	5.0	pIC50

Binding affinities (BindingDB)

263 measured of 386 human assays (388 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL6173341	IC50	0.27 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CHEMBL5276995	IC50	0.87 nM
1-methyl-8-(5-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(trifluoromethoxy)phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide	IC50	3 nM
CHEMBL3344193	IC50	3 nM
CEP-701	KD	3.4 nM
CHEMBL4459892	IC50	3.6 nM
CHEMBL4458460	IC50	3.9 nM
CHEMBL4450624	IC50	4.3 nM
CHEMBL5179633	IC50	5 nM
CHEMBL4441121	IC50	5.1 nM
Biochemistry 469551 Compound 12	IC50	5.4 nM
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
CHEMBL4447251	IC50	5.8 nM
CHEMBL4454222	IC50	5.8 nM
CHEMBL4548940	IC50	5.9 nM
9-methyl-2-(5-(1-methylpiperidin-4-yl)-2-(trifluoromethoxy)phenylamino)-6,9-dihydro-5H-pyrrolo[3,2-h]quinazoline-7-carboxamide	IC50	6 nM
Staurosporine, 8	IC50	6.5 nM
CHEMBL4448563	IC50	6.9 nM
CHEMBL4457656	IC50	7.2 nM
CHEMBL4465062	IC50	7.3 nM
CHEMBL2401963	IC50	8 nM
CHEMBL4570557	IC50	8 nM
CHEMBL4531932	IC50	9.3 nM
CHEMBL4519294	IC50	9.4 nM
CHEMBL4292295	IC50	10 nM
CHEMBL4447495	IC50	10 nM
CHEMBL4456400	IC50	10 nM
CHEMBL4436925	IC50	10 nM
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-({[4-(pyrrolidin-1-yl)butyl]carbamoyl}amino)-1,2-thiazole-4-carboxamide	IC50	10.1 nM	US-9446026: Ocular formulations for drug-delivery to the posterior segment of the eye
CHEMBL4080819	IC50	11 nM
CHEMBL6177423	IC50	11 nM
CHEMBL6175707	IC50	11 nM
CHEMBL6173383	IC50	11 nM
CHEMBL6177264	IC50	11 nM
CHEMBL6165684	IC50	12 nM
CHEMBL6176665	IC50	12 nM
CHEMBL6163861	IC50	13 nM
CHEMBL4592698	IC50	14 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
CHEMBL6172275	IC50	15 nM
CHEMBL4166771	IC50	16 nM
CHEMBL4566834	IC50	16 nM
CHEMBL6170564	IC50	16 nM
CHEMBL6171352	IC50	16 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
CHEMBL4515187	IC50	17 nM
CHEMBL5196402	IC50	17 nM
CHEMBL4529398	IC50	18 nM

ChEMBL bioactivities

247 potent at pChembl≥5 of 254 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.09	Kd	0.81	nM	BI-2536
8.70	Ki	2	nM	CHEMBL2205426
8.70	IC50	2	nM	CHEMBL1094477
8.54	IC50	2.92	nM	BI-2536
8.47	IC50	3.4	nM	CHEMBL4166771
8.46	IC50	3.5	nM	BI-2536
8.40	IC50	3.98	nM	CHEMBL4592698
8.40	IC50	4	nM	CHEMBL522618
8.33	IC50	4.72	nM	CHEMBL4454222
8.31	IC50	4.88	nM	CHEMBL4171770
8.30	IC50	5	nM	CHEMBL2401963
8.30	IC50	5	nM	VOLASERTIB
8.30	IC50	5	nM	CHEMBL5276995
8.24	IC50	5.73	nM	CHEMBL5430344
8.20	IC50	6.32	nM	CHEMBL5435085
8.15	IC50	7	nM	CHEMBL2402081
8.15	IC50	7.06	nM	CHEMBL4175722
8.11	IC50	7.86	nM	CHEMBL4176983
8.10	IC50	8	nM	CHEMBL2401971
8.10	IC50	7.98	nM	CHEMBL4548940
8.09	IC50	8.16	nM	CHEMBL4169129
8.07	IC50	8.6	nM	CHEMBL4163892
8.05	IC50	9	nM	CHEMBL2402079
8.05	IC50	9	nM	CHEMBL2401966
8.05	IC50	9	nM	CHEMBL559845
7.99	IC50	10.17	nM	CHEMBL4168155
7.96	EC50	11	nM	VOLASERTIB
7.95	IC50	11.35	nM	CHEMBL4164012
7.92	IC50	12	nM	CHEMBL2402078
7.92	IC50	12	nM	CHEMBL2401969
7.92	IC50	12	nM	CHEMBL1095457
7.92	IC50	12	nM	CHEMBL1097022
7.90	IC50	12.72	nM	CHEMBL6173341
7.89	IC50	13	nM	CHEMBL2401968
7.87	IC50	13.55	nM	BI-2536
7.85	IC50	14	nM	CHEMBL1094478
7.82	IC50	15	nM	CHEMBL2401975
7.78	IC50	16.52	nM	CHEMBL4160611
7.78	IC50	16.8	nM	BI-2536
7.77	IC50	17	nM	CHEMBL2401974
7.76	IC50	17.41	nM	CHEMBL4174667
7.75	IC50	17.77	nM	CHEMBL4177399
7.73	IC50	18.62	nM	CHEMBL4171224
7.70	IC50	19.85	nM	CHEMBL4170176
7.68	IC50	21	nM	CHEMBL2402080
7.68	IC50	21	nM	CHEMBL2401972
7.68	IC50	21	nM	CHEMBL551079
7.66	IC50	21.77	nM	CHEMBL4162262
7.62	IC50	23.87	nM	CHEMBL4173620
7.62	IC50	24	nM	CHEMBL1094135

PubChem BioAssay actives

258 with measured affinity, of 1039 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
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625063: Binding constant for PLK2 kinase domain	kd	0.0008	uM
1-methyl-8-(2-methylanilino)-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0020	uM
3-(tert-butylamino)-4-[[2-(4-pyridin-4-ylanilino)pyrimidin-4-yl]amino]cyclobut-3-ene-1,2-dione	719093: Inhibition of recombinant PLK2 after 1 hr by scintillation counter analysis in presence of gamma-[33P]ATP	ki	0.0020	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-methylbenzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0034	uM
5-(5,6-dimethoxybenzimidazol-1-yl)-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide	1798514: PLK Kinase Assay from Article 10.1021/bi7008745: “Pharmacological and functional comparison of the polo-like kinase family: insight into inhibitor and substrate specificity.”	ki	0.0038	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxybenzamide	1610356: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0040	uM
3-(1,3-benzodioxol-5-yl)-N-[(1S)-1-phenylethyl]-[1,2]oxazolo[5,4-c]pyridin-5-amine	1798481: Plk in Vitro Assay from Article 10.1016/j.bmcl.2008.08.091: “Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors.”	ic50	0.0040	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methylbenzamide	1610356: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0047	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-ethylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0049	uM
N-[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-4-[[(7R)-7-ethyl-5-methyl-6-oxo-8-propan-2-yl-7H-pteridin-2-yl]amino]-3-methoxybenzamide	1949827: Inhibition of PLK2 (unknown origin)	ic50	0.0050	uM
(7R)-8-cyclopentyl-7-ethyl-5-methyl-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0050	uM
(7R)-8-cyclopentyl-7-ethyl-2-[2-methoxy-4-[5-(piperazin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]anilino]-5-methyl-7H-pteridin-6-one	2007990: Inhibition of PLK2 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0057	uM
(7R)-8-cyclopentyl-2-[4-[5-(1,4-diazepan-1-ylmethyl)-1,2,4-oxadiazol-3-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007990: Inhibition of PLK2 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0063	uM
(7R)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1-methylpyrazol-3-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0070	uM
N-cyclopentyl-1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0071	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(2-hydroxyethyl)benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0079	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-hydroxybenzamide	1610356: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0080	uM
(7R)-7-ethyl-5-methyl-8-[(3S)-oxolan-3-yl]-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0080	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(3-hydroxypropyl)benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0082	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-methylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0086	uM
8-anilino-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0090	uM
(7R)-7-ethyl-5-methyl-2-(2-phenylimidazol-1-yl)-8-(3,3,3-trifluoropropyl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0090	uM
7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1H-pyrazol-5-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0090	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0102	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-propylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0114	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	1798697: Enzymatic Activity Assay from Article 10.1111/j.1747-0285.2007.00594.x: “Selectivity-determining residues in Plk1.”	ic50	0.0115	uM
1-methyl-8-[2-(methylamino)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0120	uM
8-(2-aminoanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0120	uM
(7R)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1H-pyrazol-4-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0120	uM
(7R)-8-(3,3-difluorocyclobutyl)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0120	uM
(7R)-8-cyclopentyl-7-ethyl-2-[2-methoxy-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3,4-thiadiazol-2-yl]anilino]-5-methyl-7H-pteridin-6-one	2238511: Inhibition of PLK2 (unknown origin) preincubated for 1 min followed by ATP and substrate addition and measured after 60 mins by ADP-glo kinase assay	ic50	0.0127	uM
8-(3,3-difluorocyclopentyl)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0130	uM
1-methyl-8-(2-methylsulfanylanilino)-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0140	uM
7-ethyl-8-(4-fluorophenyl)-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0150	uM
N-butyl-1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0165	uM
7-ethyl-5-methyl-8-phenyl-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0170	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-propan-2-ylindole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0174	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-propylbenzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0178	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]-N-(2-methylpropyl)indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0186	uM
N-butyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0198	uM
3-[(1R)-1-[4-[(tert-butylamino)methyl]-2-(difluoromethoxy)phenyl]ethoxy]-5-imidazo[1,2-a]pyridin-3-ylthiophene-2-carboxamide	433283: Inhibition of PLK2	ic50	0.0210	uM
(7R)-7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5-methyl-8-(1-methylpyrazol-4-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0210	uM
(7R)-7-ethyl-5-methyl-8-[(3R)-oxolan-3-yl]-2-(2-phenylimidazol-1-yl)-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0210	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-(2-methylpropyl)benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0218	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0239	uM
8-(2-methoxyanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0240	uM
(7R)-7-ethyl-5-methyl-2-(2-phenylimidazol-1-yl)-8-propan-2-yl-7H-pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0250	uM
8-(2-fluoroanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480527: Inhibition of Plk2 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0270	uM
1-[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]indole-5-carboxamide	1348849: Inhibition human recombinant full length GST-tagged Plk2 expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0285	uM
7-ethyl-2-[2-(4-fluorophenyl)imidazol-1-yl]-5,7-dimethyl-8-(3,3,3-trifluoropropyl)pteridin-6-one	757393: Inhibition of GST-tagged Plk2 (unknown origin) assessed as inhibition of DEKTDDED phosphorylation at Thr1342 after 60 mins by TR-FRET assay	ic50	0.0300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	8
Estradiol	decreases expression, decreases reaction, affects expression, affects binding, increases expression (+1 more)	7
sodium arsenite	decreases expression, increases abundance, increases expression	6
Valproic Acid	affects cotreatment, increases expression, decreases expression	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	5
Tretinoin	increases expression	4
Aflatoxin B1	affects expression, increases expression	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression, affects expression	4
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
chromium hexavalent ion	affects expression, increases abundance, increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Troglitazone	decreases expression	2
Cisplatin	increases expression	2
Fluorouracil	increases expression, affects reaction, increases reaction	2
Ozone	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	decreases expression, increases expression	2
Sodium Selenite	increases expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
echimidine	affects expression, increases metabolic processing	1
dicrotophos	decreases expression	1
beta-N-methylamino-L-alanine	decreases expression	1
lasiocarpine	increases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1

ChEMBL screening assays

270 unique, capped per target: 268 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1043816	Binding	Residual activity of SNK at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — *Bioorg Med Chem*
CHEMBL4677357	ADMET	Inhibition of FITC-Ahx-DPPLHSpTAI-NH2 binding to Plk2 PBD (unknown origin) expressed in bacterial expression system measured after 30 mins by fluorescence polarization assay	Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1. — *J Med Chem*
CHEMBL5209953	Functional	Affinity Phenotypic Cellular interaction (Alamar blue proliferation assay (growth inhibiton of BRO cancer cells)) EUB0000669a PLK2	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

11 cell lines: 10 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1DZ	Abcam HCT 116 PLK2 KO	Cancer cell line	Male
CVCL_B2B7	Abcam HeLa PLK2 KO	Cancer cell line	Female
CVCL_D7XW	Ubigene A-549 PLK2 KO	Cancer cell line	Male
CVCL_D8TD	Ubigene HCT 116 PLK2 KO	Cancer cell line	Male
CVCL_D9NU	Ubigene HEK293 PLK2 KO	Transformed cell line	Female
CVCL_E0L9	Ubigene HeLa PLK2 KO	Cancer cell line	Female
CVCL_TE62	HAP1 PLK2 (-)	Cancer cell line	Male
CVCL_TE63	HAP1 PLK2 (-) 1	Cancer cell line	Male
CVCL_TE64	HAP1 PLK2 (-) 2	Cancer cell line	Male
CVCL_TE65	HAP1 PLK2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

60 trials:

NCT	Phase	Status	Title
NCT00556283	Phase 4	COMPLETED	RCT: STARR vs Biofeedback
NCT00226044	Phase 3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
NCT03127345	Phase 2	WITHDRAWN	Omega 3 Fatty Acid Treatment for Pediatric Musculoskeletal Health
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02466451	Not specified	COMPLETED	Study in Children With the Diagnosis of Congenital Diaphragmatic Hernia (CDH) and Oesophageal Atresia (EA)
NCT02525705	Not specified	COMPLETED	Dumping Syndrome After Operation of Esophageal Atresia Type III
NCT02883725	Not specified	COMPLETED	National Register of Oesophageal Atresia
NCT03023865	Not specified	UNKNOWN	Individualized Management for Long Gap Esophageal Atresia
NCT03415893	Not specified	COMPLETED	High-resolution Esophageal Manometry
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03615495	Not specified	COMPLETED	Flourish™ Pediatric Esophageal Atresia
NCT03619408	Not specified	UNKNOWN	Management of Esophagitis Following Repair of Esophageal Atresia
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair
NCT03767673	Not specified	UNKNOWN	Cardiorespiratory Performance and Pulmonary Microbiome in Patients After Repair of Esophageal Atresia
NCT03999008	Not specified	UNKNOWN	Oral Viscous Budesonide in Anastomotic Stricture After Esophageal Atresia Repair (OVB in EA)
NCT04072419	Not specified	UNKNOWN	Application of Enhanced Recovery After Surgery for Congenital Esophageal Atresia During Perioperative Period
NCT04136795	Not specified	UNKNOWN	Evaluation of the Respiratory Impact After Conventional or Minimally Invasive Esophageal Atresia Surgery
NCT04259528	Not specified	UNKNOWN	Endoscopic Ultrasound Findings in Esophageal Atresia Following Surgical Repair
NCT04522193	Not specified	RECRUITING	Dumping Syndrome and Esophageal Atresia
NCT04901546	Not specified	COMPLETED	Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome
NCT04932746	Not specified	COMPLETED	The Effect of Dexmedetomidine on Oxygen During One Lung Ventilation in Pediatric Surgery.
NCT05129930	Not specified	COMPLETED	Fluid Overload and Pulmonary Function
NCT05527873	Not specified	COMPLETED	Respiratory Complications of Operated Esophageal Atresia in Children
NCT05995171	Not specified	RECRUITING	Long Term Outcome of Easophageal Atresia : Transmics Profiles in Adolescence
NCT06073158	Not specified	COMPLETED	Molecular Signatures of Esophageal Atresia
NCT06208449	Not specified	UNKNOWN	Robotic Versus Thoracoscopy Versus Thoracotomy Repair for Congenital Esophageal Atresia
NCT06335862	Not specified	ENROLLING_BY_INVITATION	Primary Posterior Tracheopexy Prevents Tracheal Collapse
NCT06731855	Not specified	RECRUITING	An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels
NCT06860919	Not specified	RECRUITING	Prospective Evaluation of the Results of Multidisciplinary Follow-up After a Transitional Consultation for Esophageal Atresia
NCT06975982	Not specified	RECRUITING	Symptoms, Pulmonary Function, Muscle Strength, Exercise Capacity, and Frailty in Esophageal Atresia vs. Healthy Peers
NCT07100379	Not specified	RECRUITING	Balloon Inflation Time for Esophageal Strictures (BITES): A Randomized Multi-Center Study
NCT07210736	Not specified	NOT_YET_RECRUITING	Brazilian Multicenter Study on Esophageal Atresia
NCT03223480	Phase 2/3	COMPLETED	EUS - Guided Balloon-occluded Gastrojejunostomy Bypass
NCT01139853	Early Phase 1	COMPLETED	Post-Operative Impact of Nasogastric Tubes on Rates of Emesis in Infants Diagnosed With Pyloric Stenosis
NCT00144924	Not specified	TERMINATED	Open vs Laparoscopic Pyloromyotomy for Pyloric Stenosis
NCT00409734	Not specified	COMPLETED	Frequency of Formula Change Prior to the Accurate Diagnosis of Pyloric Stenosis
NCT00487552	Not specified	TERMINATED	Magnetic Anastomosis Device Relief of Malignant Gastric Outlet Obstruction
NCT00991614	Not specified	COMPLETED	EVOLUTION® Duodenal Stent for Duodenal or Gastric Outlet Obstruction Caused by Malignant Neoplasms
NCT01839292	Not specified	COMPLETED	ComVi and D-type Stent in Malignant GOO
NCT02299258	Not specified	COMPLETED	Gastric Outlet Obstructions Tailored Covered Stents for GOO
NCT02359305	Not specified	COMPLETED	Institutional Audit of the Use of Intravenous Acetaminophen in Infants Undergoing Pyloromyotomy
NCT02775214	Not specified	TERMINATED	Conventional Direct Laryngoscopy Vs. Video Laryngoscopy With The C-MAC For Pyloromyotomy
NCT03259763	Not specified	COMPLETED	EUS-GE vs ES for Palliation of Gastric Outlet Obstruction
NCT03650842	Not specified	COMPLETED	Changes in Cerebral Oxygenation During Laparoscopic Pyloromyotomy
NCT03823690	Not specified	COMPLETED	EPASS Versus Uncovered Duodenal Stent for Unresectable Malignant Gastric Outlet Obstruction.
NCT04660695	Not specified	COMPLETED	Nasobiliary Drain Assisted EUS-guided Gastroenterostomies in Unresectable Malignant Gastric Outlet Obstruction
NCT04813055	Not specified	RECRUITING	Prospective Registry Of Therapeutic EndoscopiC ulTrasound
NCT05041608	Not specified	UNKNOWN	Endoscopic Surgery for Gastrointestinal Disorders: A Multicenter Registry Study
NCT05548114	Not specified	ACTIVE_NOT_RECRUITING	Randomized Trial of EUS-guided Gastrojejunostomy and Surgical Gastrojejunostomy in Gastric Outlet Obstruction
NCT05561907	Not specified	RECRUITING	Enteral Anastomosis for the Treatment of Gastric Outlet Obstruction: A Randomized Controlled Study Comparing Endoscopic Versus Surgical Gastrojejunostomy
NCT05605327	Not specified	UNKNOWN	EUS-guided Versus Laparoscopic Gastrojejunostomy for Malignant Gastric Outlet Obstruction
NCT05640947	Not specified	RECRUITING	Endoscopic Ultrasound-guided Large Diameter Lumen-apposing Metal Stent Gastro-gastrostomy for Bypass Reversal in Patients With Roux-en-y Gastric Bypass
NCT05644951	Not specified	COMPLETED	Clinical Trial of EPASS With Hot AXIOS System
NCT06071507	Not specified	RECRUITING	Management of Malignant Gastric Outlet Obstruction Between Surgery and Endoscopy
NCT06174805	Not specified	SUSPENDED	AXIOS™ Gastroenterostomy for Gastric Outlet Obstruction IDE
NCT07161856	Not specified	NOT_YET_RECRUITING	Novel Balloon-Assisted vs Direct Technique in EUS-Guided Gastroenterostomy
NCT07317076	Not specified	RECRUITING	GT Metabolic Magnet System in Adults With Gastrointestinal Disorders
NCT07609511	Not specified	RECRUITING	Magnet System Gastric Outlet Obstruction Study
NCT07749326	Not specified	RECRUITING	Malignant Gastric Outlet Obstruction Study With Stomach Partitioning (GO-PART)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.