PLK3

Summary

PLK3 (polo like kinase 3, HGNC:2154) is a protein-coding gene on chromosome 1p34.1, encoding Serine/threonine-protein kinase PLK3 (Q9H4B4). Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly.

The protein encoded by this gene is a member of the highly conserved polo-like kinase family of serine/threonine kinases. Members of this family are characterized by an amino-terminal kinase domain and a carboxy-terminal bipartite polo box domain that functions as a substrate-binding motif and a cellular localization signal. Polo-like kinases are important regulators of cell cycle progression. This gene has also been implicated in stress responses and double-strand break repair. In human cell lines, this protein is reported to associate with centrosomes in a microtubule-dependent manner, and during mitosis, the protein becomes localized to the mitotic apparatus. Expression of a kinase-defective mutant results in abnormal cell morphology caused by changes in microtubule dynamics and mitotic arrest followed by apoptosis.

Source: NCBI Gene 1263 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 117 total
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004073

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2154
Approved symbol	PLK3
Name	polo like kinase 3
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	FNK, PRK
Ensembl gene	ENSG00000173846
Ensembl biotype	protein_coding
OMIM	602913
Entrez	1263

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding_CDS_not_defined, 5 protein_coding

ENST00000372201, ENST00000461358, ENST00000461769, ENST00000465443, ENST00000476731, ENST00000492398, ENST00000493100, ENST00000850614, ENST00000854219, ENST00000854220, ENST00000942821

RefSeq mRNA: 1 — MANE Select: NM_004073 NM_004073

CCDS: CCDS515

Canonical transcript exons

ENST00000372201 — 15 exons

Exon	Start	End
ENSE00001186566	44804650	44804779
ENSE00001457170	44800377	44800673
ENSE00003490144	44802760	44802855
ENSE00003535973	44800840	44800947
ENSE00003549705	44805487	44805990
ENSE00003555765	44804163	44804246
ENSE00003573516	44804339	44804501
ENSE00003596846	44801622	44801751
ENSE00003638866	44805266	44805379
ENSE00003659322	44803268	44803391
ENSE00003665429	44802955	44803153
ENSE00003673257	44801845	44801932
ENSE00003686972	44803931	44804024
ENSE00003691566	44801036	44801152
ENSE00003694486	44803600	44803691

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 94.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.9366 / max 3620.3246, expressed in 1814 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2645	62.2768	1811
2644	0.5694	300
2646	0.0904	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.04	gold quality
mucosa of stomach	UBERON:0001199	93.92	gold quality
ascending aorta	UBERON:0001496	93.12	gold quality
thoracic aorta	UBERON:0001515	92.97	gold quality
left uterine tube	UBERON:0001303	92.83	gold quality
gall bladder	UBERON:0002110	92.36	gold quality
skin of abdomen	UBERON:0001416	92.06	gold quality
upper lobe of left lung	UBERON:0008952	92.06	gold quality
descending thoracic aorta	UBERON:0002345	91.91	gold quality
monocyte	CL:0000576	91.84	gold quality
omental fat pad	UBERON:0010414	91.77	gold quality
peritoneum	UBERON:0002358	91.68	gold quality
mononuclear cell	CL:0000842	91.13	gold quality
lower esophagus mucosa	UBERON:0035834	90.82	gold quality
upper lobe of lung	UBERON:0008948	90.79	gold quality
leukocyte	CL:0000738	90.57	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.13	gold quality
secondary oocyte	CL:0000655	90.07	gold quality
aorta	UBERON:0000947	89.36	gold quality
skin of leg	UBERON:0001511	89.33	gold quality
right uterine tube	UBERON:0001302	89.20	gold quality
esophagus mucosa	UBERON:0002469	89.13	gold quality
right lung	UBERON:0002167	88.61	gold quality
right coronary artery	UBERON:0001625	88.60	gold quality
left coronary artery	UBERON:0001626	88.57	gold quality
granulocyte	CL:0000094	88.23	gold quality
adenohypophysis	UBERON:0002196	88.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.01	gold quality
ectocervix	UBERON:0012249	87.57	gold quality
coronary artery	UBERON:0001621	87.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F2, E2F3, TP53

miRNA regulators (miRDB)

47 targeting PLK3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
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-3934-3P	99.76	65.51	1351
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4292	99.16	65.57	1767

Literature-anchored findings (GeneRIF, showing 40)

• These results suggest that Polo-like kinase regulates the dissociation of cohesin from chromosomes early in mitosis. (cohesin) (PMID:11931760)
• Results suggest that Plk3 plays an important role in the regulation of microtubule dynamics and centrosomal function in the cell and that deregulated expression of Plk3 results in cell cycle arrest and apoptosis. (PMID:11971976)
• Plk3 is a multifunctional protein that associates with multiple complexes and that contributes to response to stress incurred by DNA damage and mitotic spindle disruption, albeit via different pathways. (PMID:12242661)
• Plk3 is rapidly activated by reactive oxygen species in fibroblasts, correlating with increased p53 protein levels. Plk3 physically interacts with Chk2 and the interaction is enhanced upon DNA damage. (PMID:12548019)
• Plk3 has a role in coordinating the translocation and perhaps the timing of both Cdc25C and its target Cdc2/cyclin B to the nucleus upon entry into mitosis (PMID:14968113)
• Plk3 may be a key protein kinase mediating MEK1 function in the Golgi fragmentation pathway during cell division. (PMID:15021912)
• Taken together, our study suggests that Plk3 and Aurora A kinases may lie in the same regulatory pathway and that Plk3 and Aurora A as well as BubR1 may play an important role in polyploidization and megakaryocytic differentiation. (PMID:15190214)
• Plk3 is a RelA-NF-kappaB-regulated gene that induces apoptosis in both p53-dependent and -independent signaling pathways (PMID:15671037)
• Introduction of plk3 gene into tumor cells with RV vectors can slow down cell proliferation, prevent cells into cell cycle and protect cells from apoptosis in serum-free culture. (PMID:16388739)
• the Polo box domain of Plk3 is more potent in inhibiting cell proliferation and inducing apoptosis than that of Plk1 (PMID:16478733)
• Plk3 is in a pathway linking ATM, Plk3, Chk2, Cdc25C and Cdc2 in cellular response to DNA damage. (PMID:16481012)
• Plk3 localizes to the nucleolus and is involved in regulation of the G1/S phase transition. (PMID:17264206)
• Results show that Plk3 mediates UV irradiation-induced c-Jun activation by phosphorylating c-Jun, suggesting that Plk3 plays an important role in mediating programmed cell death of corneal epithelial cells after UV irradiation. (PMID:17804415)
• topoisomerase IIalpha is a novel physiological substrate for Plk3, and Plk1 and Plk3 play different roles in cell-cycle regulation. (PMID:18062778)
• hypoxia/reoxygenation induces Plk3 activation instead of the JNK effect to directly phosphorylate and activate c-Jun, subsequently contributing to apoptosis in human corneal epithelial cells (PMID:18650425)
• The Plk3-VRK1 kinase module might represent two consecutive steps of a signaling cascade that participates in the regulation of Golgi fragmentation. (PMID:19103756)
• The Plk3 overexpression suppressed cellular growth in a long-term colony-forming assay. And overexpression of Plk3 caused long-term growth suppression in Ras-transformed NIH3T3. (PMID:19556223)
• upregulation of CIB1 in cancer cells may inhibit Plk3 activity, leading to abnormal cell cycle regulation in breast cancer cells. (PMID:20473878)
• Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha (PMID:20889502)
• Plk3 as a new player in the regulation of the PI3K/PDK1/Akt signaling axis by phosphorylation and stabilization of PTEN. (PMID:20940307)
• Calcium- and integrin-binding protein 1 regulates microtubule organization and centrosome segregation through polo like kinase 3 during cell cycle progression. (PMID:20951827)
• hyperosmotic stress can activate the Plk3 signaling pathway that subsequently regulates the AP-1 complex by directly phosphorylating ATF-2 independent from the effects of JNK and p38 activation. (PMID:21098032)
• Bcl-xL phosphorylation at Ser49 by polo-like kinase 3 during cell cycle progression and checkpoints (PMID:21840391)
• Here, the authors report phosphorylation of Thr4 by Polo-like kinase 3 in mammalian cells. (PMID:22549466)
• have identified and validated as in vitro PLK2 and PLK3 substrates HSP90, GRP-94, beta-tubulin, calumenin, and 14-3-3 epsilon (PMID:22828320)
• hyperosmotic stress-activated Plk3 elicited gammaH2AX. (PMID:25202016)
• Plk3 binds to CtIP phosphorylated at S327 via its Polo box domains, which is necessary for robust damage-induced CtIP phosphorylation at S327 and subsequent CtIP phosphorylation at T847. (PMID:25267294)
• PLK3 predominantly is expressed in Cholangiocarcinomas (CCA) cells and that high PLK3 expression correlates with prolonged overall survival. (PMID:25818805)
• The role of Plk3 in oncogenesis: the aberrant expression of Plk3 was found in different types of tumors. (PMID:25915845)
• Plk3 is involved in the inhibition of cell proliferation and tumorigenesis, which may occur via interactions with p21. (PMID:26352014)
• Data suggest that HOXA-AS2 could be an oncogene for gastric cancer partly through suppressing P21, PLK3, and DDIT3 expression. (PMID:26384350)
• the differential effects of hypoxic stress on Plk3 activity in Human Limbal Stem and HCE cells. Instead of apoptosis, hypoxic stress suppresses Plk3 activity to protect limbal stem cells from death and to allow the process of Human Limbal Stem cell differentiation. (PMID:27281822)
• Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional death-inducing signaling complex for Plk3 activation. (PMID:27325299)
• Those data indicate that the overexpression of PLK3-mediated degradation of abnormal PrP is largely dependent on chaperone-mediated autophagy pathway. (PMID:27344333)
• Data indicate that elevated levels of Polo-like kinase 3 (Plk3)and pT273 caspase-8 are correlated with favorable clinical outcome in patients with anal squamous cell carcinoma (anal SCC) treated with concomitant chemoradiotherapy (CRT). (PMID:27462786)
• study revealed an interesting mutual regulation between Plk3 and SIAH2 and uncovered a regulatory network that functions to fine-tune the cellular hypoxic response. (PMID:28515325)
• Phosphorylation of PLK3 Is Controlled by Protein Phosphatase 6. (PMID:32575753)
• The oncogenicity of tumor-derived mutant p53 is enhanced by the recruitment of PLK3. (PMID:33514736)
• Identification and assessment of PLK1/2/3/4 in lung adenocarcinoma and lung squamous cell carcinoma: Evidence from methylation profile. (PMID:34080290)
• PLK3 promotes the proneural-mesenchymal transition in glioblastoma via transcriptional regulation of C5AR1. (PMID:37568042)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plk3	ENSDARG00000038754
mus_musculus	Plk3	ENSMUSG00000028680
rattus_norvegicus	Plk3	ENSRNOG00000018484

Paralogs (4): PLK4 (ENSG00000142731), PLK2 (ENSG00000145632), PLK1 (ENSG00000166851), PLK5 (ENSG00000185988)

Protein

Protein identifiers

Serine/threonine-protein kinase PLK3 — Q9H4B4 (reviewed: Q9H4B4)

Alternative names: Cytokine-inducible serine/threonine-protein kinase, FGF-inducible kinase, Polo-like kinase 3, Proliferation-related kinase

All UniProt accessions (1): Q9H4B4

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1.

Subunit / interactions. Interacts (via the POLO-box domain) with CIB1; leading to inhibit PLK3 kinase activity. Interacts with GOLGB1.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Golgi apparatus. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Transcripts are highly detected in placenta, lung, followed by skeletal muscle, heart, pancreas, ovaries and kidney and weakly detected in liver and brain. May have a short half-live. In cells of hematopoietic origin, strongly and exclusively detected in terminally differentiated macrophages. Transcript expression appears to be down-regulated in primary lung tumor.

Post-translational modifications. Phosphorylated in an ATM-dependent manner following DNA damage. Phosphorylated as cells enter mitosis and dephosphorylated as cells exit mitosis.

Domain organisation. The POLO box domains act as phosphopeptide-binding module that recognizes and binds serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK3 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. The POLO box domains mediate localization to the centrosome.

Induction. Cytokine and cellular adhesion trigger induction. Down-regulated in a majority of lung carcinoma samples.

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

RefSeq proteins (1): NP_004064* (*=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
IPR042703	PLK3_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)
• EC 2.7.11.23 — [RNA-polymerase]-subunit kinase (BRENDA: 12 organisms, 155 substrates, 47 inhibitors, 15 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0002–0.0076	13
CDC25C	0.0006–0.0008	6
ATP	0.01–0.06	6
HEPTA-SIX PEPTIDE	0.189–0.2	2
L-ARG-HEPTA PEPTIDE	0.212–0.243	2
CASEIN	0.0014	1
CTD-CONTAINING FUSION PROTEIN	0.0002	1
GTP	0.18	1
SYNTHETIC PEPTIDE	0.15	1
[DNA-DIRECTED RNA POLYMERASE]	0.0001	1

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (52 total): helix 13, sequence variant 7, sequence conflict 7, strand 7, mutagenesis site 4, domain 3, turn 3, binding site 2, region of interest 2, compositionally biased region 2, chain 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4B6L	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4B4-F1	80.95	0.61

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): 185 (proton acceptor)

Ligand- & substrate-binding residues (2): 91; 68–76

Mutagenesis-validated functional residues (4):

Position	Phenotype
91	kinase defective mutant, abolishes activity.
203	kinase defective mutant, abolishes activity.
219	kinase-defective mutant.
467–468	abolishes localization to the centrosome and ability to induce the g2/m arrest.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A

MSigDB gene sets: 411 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, SHEPARD_CRASH_AND_BURN_MUTANT_UP, MODULE_45, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_CELL_CYCLE_PHASE_TRANSITION, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_16

GO Biological Process (28): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), negative regulation of transcription by RNA polymerase II (GO:0000122), response to reactive oxygen species (GO:0000302), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), response to osmotic stress (GO:0006970), DNA damage response (GO:0006974), mitotic spindle organization (GO:0007052), endomitotic cell cycle (GO:0007113), response to radiation (GO:0009314), DNA damage response, signal transduction by p53 class mediator (GO:0030330), cytoplasmic microtubule organization (GO:0031122), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), regulation of cytokinesis (GO:0032465), negative regulation of apoptotic process (GO:0043066), mitotic G1/S transition checkpoint signaling (GO:0044819), regulation of cell division (GO:0051302), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), Golgi disassembly (GO:0090166), positive regulation of intracellular protein transport (GO:0090316), regulation of signal transduction by p53 class mediator (GO:1901796), positive regulation of chaperone-mediated autophagy (GO:1904716), positive regulation of autophagy (GO:0010508), regulation of cell cycle process (GO:0010564), regulation of cell communication (GO:0010646), regulation of signaling (GO:0023051), positive regulation of protein catabolic process (GO:0045732)

GO Molecular Function (9): p53 binding (GO:0002039), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), 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 (12): kinetochore (GO:0000776), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi stack (GO:0005795), centrosome (GO:0005813), dendrite (GO:0030425), neuronal cell body (GO:0043025), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Cycle Genes	1
Regulation of TP53 Activity	1
p53-Independent G1/S DNA Damage Checkpoint	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	4
intracellular membraneless organelle	3
cellular anatomical structure	3
mitotic cell cycle phase transition	2
response to abiotic stimulus	2
protein kinase activity	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cell cycle G1/S phase transition	1
cell cycle G2/M phase transition	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
response to oxidative stress	1
response to oxygen-containing compound	1
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to stress	1
cellular response to stress	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G1/S transition of mitotic cell cycle	1

Protein interactions and networks

STRING

2767 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLK3	CDC5L	Q99459	887
PLK3	CDC25C	P30307	783
PLK3	CIB1	Q99828	664
PLK3	IER3	P46695	536
PLK3	DUSP5	Q16690	478
PLK3	ATM	Q13315	470
PLK3	CASP8	Q14790	465
PLK3	FADD	Q13158	451
PLK3	DUSP6	Q16828	439
PLK3	SPRY4	Q9C004	434
PLK3	TP53	P04637	431
PLK3	FAS	P25445	428
PLK3	FOSL1	P15407	409
PLK3	GADD45A	P24522	403
PLK3	PHLDA1	Q8WV24	399

IntAct

38 interactions, top by confidence:

A	B	Type	Score
	VRK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.730
VRK1	PLK3	psi-mi:“MI:0915”(physical association)	0.650
VRK1	PLK3	psi-mi:“MI:0403”(colocalization)	0.650
PLK3	VRK1	psi-mi:“MI:0403”(colocalization)	0.650
PLK3	VRK1	psi-mi:“MI:0915”(physical association)	0.650
PLK3	VRK1	psi-mi:“MI:0407”(direct interaction)	0.650
PRNP	PLK3	psi-mi:“MI:0915”(physical association)	0.570
PRNP	PLK3	psi-mi:“MI:0403”(colocalization)	0.570
POU2F1	PLK3	psi-mi:“MI:0915”(physical association)	0.560
MFF	PLK3	psi-mi:“MI:0915”(physical association)	0.560
PLK3	LSM5	psi-mi:“MI:0915”(physical association)	0.560
RNF141	PLK3	psi-mi:“MI:0915”(physical association)	0.560
RAD52	PLK3	psi-mi:“MI:0915”(physical association)	0.560
	PLK3	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PLK3	TRIP13	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
PLK3	AIP	psi-mi:“MI:0914”(association)	0.350
PLK3	LSM5	psi-mi:“MI:0915”(physical association)	0.000
PLK3	RAD52	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): POU2F1 (Two-hybrid), TRIP13 (Two-hybrid), BCL2L1 (Biochemical Activity), HIF1A (Reconstituted Complex), HIF1A (Biochemical Activity), HIF1A (Affinity Capture-Western), PLK3 (Affinity Capture-Western), PLK1 (Two-hybrid), CHEK2 (Two-hybrid), RRM2 (Two-hybrid), PPM1A (Two-hybrid), TENC1 (Two-hybrid), SLX4 (Two-hybrid), CHEK2 (Affinity Capture-Western), CHEK2 (Reconstituted Complex)

ESM2 similar proteins: A1A4I4, A5PKD8, A6NED2, A8MQ27, O35465, O60294, O75808, O94819, O95382, P70268, Q0MW30, Q14318, Q16512, Q2T9J0, Q32NY4, Q32P44, Q3B7U9, Q3MHW0, Q3U5Q7, Q3USL1, Q4R828, Q561R2, Q5EBM0, Q5EBP3, Q5PQP9, Q60806, Q63433, Q6PAT0, Q7T0L4, Q8BNW9, Q8BTU7, Q8BYR1, Q8IYL2, Q8N5A5, Q8NEP7, Q8VC03, Q8VHS5, Q8WXI3, Q91ZT7, Q96C12

Diamond homologs: A0A8I3S724, A2VDZ4, A3B529, A4IGM9, A5GFW1, A7SNN5, A8BPK8, A8WYE4, B0WAU8, B2GUY1, B3DL84, B3M6I4, B3NE99, B4HBU3, B4IAQ8, B4J3F1, B4KYX8, B4LDJ6, B4MXR8, B4PDM5, B4QK53, D7UQM5, O00444, O14965, O22971, O55099, O59790, O64629, O65554, O70126, O88445, O97143, P0C8M8, P32562, P34331, P38991, P50528, P52304, P53350, P53351

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
PLK3	“up-regulates activity”	TP53	phosphorylation
PLK3	up-regulates	CDC25C	phosphorylation
PLK3	up-regulates	JUN	phosphorylation
PLK3	up-regulates	TOP2A	phosphorylation
PLK3	down-regulates	CDC25A	phosphorylation
PLK3	up-regulates	ATF2	phosphorylation
PLK3	“down-regulates activity”	PTEN	phosphorylation
PLK3	up-regulates	BCL2L1	phosphorylation
PLK3	down-regulates	HIF1A	phosphorylation
PLK3	up-regulates	VRK1	phosphorylation
PLK3	“down-regulates activity”	SNCA	phosphorylation
PLK3	“down-regulates activity”	SNCB	phosphorylation
PLK3	“down-regulates activity”	TP73	phosphorylation
PLK3	“up-regulates activity”	H2AX	phosphorylation
PLK3	unknown	CDC25C	phosphorylation
PLK3	“up-regulates activity”	CASP8	phosphorylation
PLK3	“up-regulates activity”	CHEK2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	4
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1645 predictions. Top by Δscore:

Variant	Effect	Δscore
1:44800835:CACA:C	acceptor_loss	1.0000
1:44800837:CAGGG:C	acceptor_loss	1.0000
1:44800838:A:AG	acceptor_gain	1.0000
1:44800838:AG:A	acceptor_gain	1.0000
1:44800838:AGG:A	acceptor_gain	1.0000
1:44800838:AGGG:A	acceptor_gain	1.0000
1:44800838:AGGGG:A	acceptor_gain	1.0000
1:44800839:G:GA	acceptor_gain	1.0000
1:44800839:GG:G	acceptor_gain	1.0000
1:44800839:GGG:G	acceptor_gain	1.0000
1:44800839:GGGG:G	acceptor_gain	1.0000
1:44800839:GGGGG:G	acceptor_gain	1.0000
1:44800944:GAAG:G	donor_gain	1.0000
1:44800948:G:GG	donor_gain	1.0000
1:44801034:A:AG	acceptor_gain	1.0000
1:44801035:G:GG	acceptor_gain	1.0000
1:44801159:GATG:G	donor_gain	1.0000
1:44801177:G:T	donor_gain	1.0000
1:44801182:GA:G	donor_gain	1.0000
1:44801184:G:GG	donor_gain	1.0000
1:44801189:G:GT	donor_gain	1.0000
1:44801617:TGCA:T	acceptor_loss	1.0000
1:44801618:GCAGT:G	acceptor_loss	1.0000
1:44801619:CA:C	acceptor_loss	1.0000
1:44801620:A:AG	acceptor_gain	1.0000
1:44801620:AGTC:A	acceptor_loss	1.0000
1:44801621:G:GA	acceptor_gain	1.0000
1:44801621:GT:G	acceptor_gain	1.0000
1:44801621:GTC:G	acceptor_gain	1.0000
1:44801621:GTCC:G	acceptor_gain	1.0000

AlphaMissense

4166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44800846:T:C	F73L	1.000
1:44800847:T:C	F73S	1.000
1:44800847:T:G	F73C	1.000
1:44800848:C:A	F73L	1.000
1:44800848:C:G	F73L	1.000
1:44800902:A:C	K91N	1.000
1:44800902:A:T	K91N	1.000
1:44801143:C:G	C142W	1.000
1:44801737:G:C	R184P	1.000
1:44801740:A:C	D185A	1.000
1:44801740:A:T	D185V	1.000
1:44801849:T:A	N190K	1.000
1:44801849:T:G	N190K	1.000
1:44801887:A:C	D203A	1.000
1:44801887:A:G	D203G	1.000
1:44801887:A:T	D203V	1.000
1:44801888:T:A	D203E	1.000
1:44801888:T:G	D203E	1.000
1:44802836:T:A	W244R	1.000
1:44802836:T:C	W244R	1.000
1:44804395:T:A	W467R	1.000
1:44804395:T:C	W467R	1.000
1:44800840:G:A	G71R	0.999
1:44800840:G:C	G71R	0.999
1:44800840:G:T	G71W	0.999
1:44800841:G:A	G71E	0.999
1:44800846:T:A	F73I	0.999
1:44800846:T:G	F73V	0.999
1:44800850:C:A	A74D	0.999
1:44800857:C:G	C76W	0.999

dbSNP variants (sampled 300 via entrez): RS1000516764 (1:44806329 G>A), RS1000737791 (1:44802384 A>T), RS1001244228 (1:44801327 A>G), RS1001862513 (1:44800962 A>C), RS1003130508 (1:44802435 G>A), RS1003244660 (1:44804561 C>G,T), RS1003246129 (1:44799540 C>A,G,T), RS1003298495 (1:44799441 T>A), RS1003870489 (1:44803771 G>A), RS1004156114 (1:44799527 T>A,G), RS1004368945 (1:44805999 C>G,T), RS1004431591 (1:44800051 G>A), RS1004443113 (1:44799774 C>T), RS1004649755 (1:44801353 G>A), RS1005159397 (1:44801554 A>G,T)

Disease associations

OMIM: gene MIM:602913 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4897 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 35,875 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL1233528	VOLASERTIB	3	1,511
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL603469	LESTAURTINIB	3
CHEMBL1738758	ONVANSERTIB	2	780
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL1980391	RG-1530	1	37
CHEMBL259084	MLN-8054	1	2,430
CHEMBL260933	GS 6201	1	298
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
BI-2536	Inhibition	8.05	pIC50
onvansertib	Inhibition	5.0	pIC50

Binding affinities (BindingDB)

41 measured of 47 human assays (49 total across all organisms); most potent 41 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	0.8 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-methoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	1 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-{6-[(2S)-2,3-dihydroxypropoxy]-1H-1,3-benzodiazol-1-yl}thiophene-2-carboxamide	IC50	1 nM
Staurosporine	KD	1.7 nM
BMCL191018 Compound 2	IC50	2 nM
3-[(2-chlorophenyl)methoxy]-5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	2 nM
5-{6-[(1-methylpiperidin-4-yl)oxy]-1H-1,3-benzodiazol-1-yl}-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	IC50	2 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-{6-[(1-methylpiperidin-4-yl)oxy]-1H-1,3-benzodiazol-1-yl}thiophene-2-carboxamide	IC50	2 nM
5-(6-methoxy-1H-1,3-benzodiazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	IC50	3 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-{6-[(2S)-2-hydroxy-3-(pyrrolidin-1-yl)propoxy]-1H-1,3-benzodiazol-1-yl}thiophene-2-carboxamide	IC50	3 nM
5-[6-(piperidin-4-yloxy)-1H-1,3-benzodiazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	IC50	3 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-{[(4S)-1-methylazepan-4-yl]oxy}-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	3 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-{6-[3-(dimethylamino)propoxy]-1H-1,3-benzodiazol-1-yl}thiophene-2-carboxamide	IC50	4 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-{[(4R)-1-methylazepan-4-yl]oxy}-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	4 nM
4-{[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino}-N-(1-methylpiperidin-4-yl)benzamide	IC50	5 nM
Biochemistry 469551 Compound 12	IC50	5.4 nM
H-1152	KI	6 nM
1-tert-butyl-3-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine	IC50	6 nM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-{6-[(1-methylpiperidin-4-yl)methoxy]-1H-1,3-benzodiazol-1-yl}thiophene-2-carboxamide	IC50	6 nM
5-{6-[(1-methylpiperidin-4-yl)methoxy]-1H-1,3-benzodiazol-1-yl}-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	IC50	7 nM
4-{[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino}-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	8 nM	US-8598172: Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors
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
Biochemistry 469551 Compound 11	IC50	14 nM
3-[(1S)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	30 nM
(7R)-8-cyclopentyl-7-ethyl-5-methyl-2-[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)anilino]-7H-pteridin-6-one	IC50	32 nM	US-8598172: Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors
3-[3-chloro-5-(5-{[(1S)-1-phenylethyl]amino}pyrido[4,3-d][1,2]oxazol-3-yl)phenyl]propanamide	IC50	51 nM
1-[4-(cyclopentylamino)-2-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl]ethan-1-one	IC50	145 nM
3-(2H-1,3-benzodioxol-5-yl)-N-[(1S)-1-phenylethyl]pyrido[4,3-d][1,2]oxazol-5-amine	IC50	214 nM
1-[4-(cyclopentylamino)-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-5-yl]ethan-1-one	IC50	345 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
3-(3-methylphenyl)-N-[(1S)-1-phenylethyl]pyrido[4,3-d][1,2]oxazol-5-amine	IC50	549 nM
3-(4-{4-aminothieno[2,3-d]pyrimidin-5-yl}phenyl)-1-(3-methylphenyl)urea	IC50	720 nM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
N-{2-[3-chloro-5-(3-methyl-6-{[(1S)-1-phenylethyl]amino}-1H-pyrazolo[4,3-c]pyridin-1-yl)phenyl]phenyl}acetamide	IC50	6800 nM
2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	IC50	13100 nM	US-9505780: Thienopyranones as kinase and epigenetic inhibitors
(3E)-5-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]pyridin-3-yl}-3-(furan-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one	KI	31000 nM

ChEMBL bioactivities

443 potent at pChembl≥5 of 466 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.79	IC50	1.61	nM	BI-2536
8.70	Ki	2	nM	CHEMBL2205426
8.40	Kd	4	nM	BI-2536
8.38	IC50	4.12	nM	CHEMBL6173341
8.31	IC50	4.89	nM	CHEMBL5435085
8.30	IC50	5	nM	CHEMBL1208892
8.30	IC50	5	nM	CHEMBL1945502
8.30	IC50	5	nM	CHEMBL1945500
8.30	Ki	5.012	nM	CHEMBL1968380
8.29	Kd	5.1	nM	R-406
8.22	IC50	6.04	nM	CHEMBL4592698
8.22	IC50	6	nM	GSK-237701A
8.22	IC50	6	nM	CHEMBL1094477
8.22	IC50	6	nM	CHEMBL1209841
8.22	IC50	6	nM	CHEMBL1209842
8.20	Ki	6.31	nM	CHEMBL244378
8.15	IC50	7	nM	CHEMBL1945501
8.12	IC50	7.56	nM	CHEMBL5430344
8.10	IC50	8	nM	CHEMBL1209605
8.10	Ki	7.943	nM	GW843682X
8.05	IC50	9	nM	GW843682X
8.05	IC50	9	nM	GW852849X
8.05	IC50	9	nM	BI-2536
8.05	IC50	9	nM	CHEMBL1945801
8.04	IC50	9.1	nM	GW843682X
8.00	IC50	10	nM	CHEMBL1209674
7.96	EC50	11	nM	VOLASERTIB
7.96	IC50	11	nM	CHEMBL1095457
7.92	IC50	12	nM	CHEMBL1945170
7.90	Ki	12.59	nM	CHEMBL1241473
7.90	Ki	12.59	nM	CHEMBL2005375
7.90	Ki	12.59	nM	CHEMBL1964399
7.89	IC50	13	nM	CHEMBL1097022
7.89	IC50	13	nM	CHEMBL1094135
7.89	IC50	13	nM	CHEMBL1209843
7.85	IC50	14	nM	CHEMBL559845
7.80	IC50	16	nM	CHEMBL1094478
7.80	IC50	16	nM	CHEMBL1209606
7.80	IC50	16	nM	CHEMBL1209676
7.80	Ki	15.85	nM	CHEMBL1978448
7.80	Ki	15.85	nM	CHEMBL1969523
7.75	IC50	18	nM	CHEMBL1945171
7.72	IC50	18.91	nM	CHEMBL4454222
7.68	IC50	20.78	nM	BI-2536
7.66	IC50	22.14	nM	CHEMBL4458460
7.62	IC50	24	nM	CHEMBL522618
7.60	IC50	25	nM	CHEMBL1209675
7.60	Ki	25.12	nM	CHEMBL396523
7.52	IC50	30.4	nM	CHEMBL4548940
7.52	IC50	30	nM	GW837331X

PubChem BioAssay actives

253 with measured affinity, of 1907 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	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	0.0010	uM
3-(tert-butylamino)-4-[[2-(4-pyridin-4-ylanilino)pyrimidin-4-yl]amino]cyclobut-3-ene-1,2-dione	719091: Inhibition of recombinant PLK3 after 1 hr by scintillation counter analysis in presence of gamma-[33P]ATP	ki	0.0020	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	2007991: Inhibition of PLK3 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0049	uM
5-[5-(2-aminopyrimidin-4-yl)benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0050	uM
9-chloro-2-[3-chloro-5-[3-(dimethylamino)propyl]anilino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione	642965: Inhibition of PLK3	ic50	0.0050	uM
9-chloro-2-[3-[3-(dimethylamino)propyl]-4-methoxyanilino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione	642965: Inhibition of PLK3	ic50	0.0050	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624933: Binding constant for PLK3 kinase domain	kd	0.0051	uM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxybenzimidazol-1-yl)thiophene-2-carboxamide	1798875: Scintillation Proximity Assay (SPA) from Article 10.1016/j.bmcl.2009.01.094: “Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.”	ic50	0.0060	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxybenzamide	1610357: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0060	uM
1-methyl-8-(2-methylanilino)-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0060	uM
5-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0060	uM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0060	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	0.0067	uM
9-chloro-2-[3-[3-(dimethylamino)propyl]-4-fluoroanilino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione	642965: Inhibition of PLK3	ic50	0.0070	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	2007991: Inhibition of PLK3 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0076	uM
5-(5-pyridin-4-ylbenzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0080	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	0.0080	uM
3-[(2-chlorophenyl)methoxy]-5-(5,6-dimethoxybenzimidazol-1-yl)thiophene-2-carboxamide	1798875: Scintillation Proximity Assay (SPA) from Article 10.1016/j.bmcl.2009.01.094: “Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.”	ic50	0.0090	uM
9-chloro-2-[3-[3-(dimethylamino)propyl]-4-(trifluoromethyl)anilino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione	642965: Inhibition of PLK3	ic50	0.0090	uM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(5-pyridin-4-ylbenzimidazol-1-yl)thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0100	uM
1-methyl-8-[2-(methylamino)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0110	uM
9-chloro-2-[3-[3-(dimethylamino)propyl]anilino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione	642965: Inhibition of PLK3	ic50	0.0120	uM
8-(2-methoxyanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0130	uM
8-(2-aminoanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0130	uM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-(1-methylpyrazol-4-yl)benzimidazol-1-yl]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0130	uM
8-anilino-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0140	uM
1-methyl-8-(2-methylsulfanylanilino)-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0160	uM
5-(6-pyridin-4-ylbenzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0160	uM
5-(5-pyridin-3-ylbenzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0160	uM
9-chloro-2-[5-[3-(dimethylamino)propyl]-2-methylanilino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione	642965: Inhibition of PLK3	ic50	0.0180	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methylbenzamide	1610357: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0189	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-fluoro-5-(2-hydroxyethoxy)benzamide	1610357: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0221	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	0.0240	uM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-pyridin-4-ylbenzimidazol-1-yl)thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0250	uM
5-methyl-7-[3-(trifluoromethyl)phenyl]-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine	344832: Inhibition of PLK3 expressed in baculovirus infected Trichoplusia ni cells	ic50	0.0300	uM
N-cyclopentyl-4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-hydroxybenzamide	1610357: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0304	uM
9-chloro-2-[[5-[3-(dimethylamino)propyl]-3-pyridinyl]amino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione	642965: Inhibition of PLK3	ic50	0.0310	uM
1-methyl-8-[2-(trifluoromethoxy)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	527998: Inhibition of PLK3	ic50	0.0320	uM
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-methoxybenzimidazol-1-yl)thiophene-2-carboxamide	1798875: Scintillation Proximity Assay (SPA) from Article 10.1016/j.bmcl.2009.01.094: “Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.”	ic50	0.0350	uM
8-(2-fluoroanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0370	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-methylbenzenesulfonamide	1348851: Inhibition human recombinant GST-tagged Plk3 catalytic domain (58 to 340 residues) expressed in baculovirus expression system after 1 hr by FRET-based Z’-Lyte assay	ic50	0.0385	uM
5-(6-pyridin-3-ylbenzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0400	uM
5-(6-methoxybenzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	1798875: Scintillation Proximity Assay (SPA) from Article 10.1016/j.bmcl.2009.01.094: “Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.”	ic50	0.0410	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-fluoro-5-(2-hydroxyethoxy)-N-methylbenzamide	1610357: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0438	uM
3-[(1S)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxybenzimidazol-1-yl)thiophene-2-carboxamide	1798875: Scintillation Proximity Assay (SPA) from Article 10.1016/j.bmcl.2009.01.094: “Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.”	ic50	0.0440	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-fluoro-5-(2-hydroxyethoxy)-N-propan-2-ylbenzamide	1610357: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0451	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-ethyl-2-fluoro-5-(2-hydroxyethoxy)benzamide	1610357: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z’-LYTE assay	ic50	0.0469	uM
[(1R,3R,5S,9R,18S)-18-(methoxymethyl)-1,5-dimethyl-6,11,16-trioxo-13,17-dioxapentacyclo[10.6.1.02,10.05,9.015,19]nonadeca-2(10),12(19),14-trien-3-yl] acetate	360389: Inhibition of recombinant Plk3 assessed as casein substrate phosphorylation	ic50	0.0480	uM
8-(2-acetamidoanilino)-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	480528: Inhibition of Plk3 assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting	ic50	0.0490	uM
5-(5-thiophen-2-ylbenzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	493667: Inhibition of full lungth PLK3 by SPA assay	ic50	0.0500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	7
Cisplatin	affects cotreatment, increases expression	5
Aflatoxin B1	affects expression, increases expression	4
bisphenol A	affects expression, affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Camptothecin	increases expression	2
Dexamethasone	affects cotreatment, decreases expression	2
Doxorubicin	increases expression	2
Estradiol	affects cotreatment, increases expression	2
Hydrogen Peroxide	affects expression	2
Lipopolysaccharides	affects response to substance, increases expression, affects reaction, decreases expression, increases cleavage	2
Methyl Methanesulfonate	increases expression	2
Cyclosporine	increases expression	2
Sodium Selenite	increases expression	2
Vitamin K 3	affects expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
Glupearl 19S	increases expression	1
echimidine	increases expression, increases metabolic processing	1
dicrotophos	increases expression	1
chloroacetaldehyde	affects expression	1
methylmercuric chloride	increases expression	1
lasiocarpine	increases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
riddelliine	increases expression, increases metabolic processing	1

ChEMBL screening assays

364 unique, capped per target: 360 binding, 3 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1038803	Binding	Residual activity of PLK3 at 10 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL1963697	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PLK3	PubChem BioAssay data set
CHEMBL4704962	ADMET	Displacement of 5-carboxyfluorescein-labeled PBD-binding peptide from PLk3 PBD (unknown origin) expressed in bacterial expression system incubated for 10 mins by fluorescence polarization assay	Development of a Polo-like Kinase-1 Polo-Box Domain Inhibitor as a Tumor Growth Suppressor in Mice Models. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7XX	Ubigene A-549 PLK3 KO	Cancer cell line	Male
CVCL_D8TE	Ubigene HCT 116 PLK3 KO	Cancer cell line	Male
CVCL_D9NV	Ubigene HEK293 PLK3 KO	Transformed cell line	Female
CVCL_E0LA	Ubigene HeLa PLK3 KO	Cancer cell line	Female
CVCL_TE67	HAP1 PLK3 (-) 1	Cancer cell line	Male
CVCL_TE68	HAP1 PLK3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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