PLK1

Summary

PLK1 (polo like kinase 1, HGNC:9077) is a protein-coding gene on chromosome 16p12.2, encoding Serine/threonine-protein kinase PLK1 (P53350). Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cy…. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

The Ser/Thr protein kinase encoded by this gene belongs to the CDC5/Polo subfamily. It is highly expressed during mitosis and elevated levels are found in many different types of cancer. Depletion of this protein in cancer cells dramatically inhibited cell proliferation and induced apoptosis; hence, it is a target for cancer therapy.

Source: NCBI Gene 5347 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 81 total — 1 pathogenic
• Druggable target: yes — 25 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_005030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9077
Approved symbol	PLK1
Name	polo like kinase 1
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166851
Ensembl biotype	protein_coding
OMIM	602098
Entrez	5347

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000300093, ENST00000562272, ENST00000562407, ENST00000564202, ENST00000564794, ENST00000564947, ENST00000567897, ENST00000568568, ENST00000570220, ENST00000885692, ENST00000922967, ENST00000922968

RefSeq mRNA: 1 — MANE Select: NM_005030 NM_005030

CCDS: CCDS10616

Canonical transcript exons

ENST00000300093 — 10 exons

Exon	Start	End
ENSE00001107226	23689860	23690367
ENSE00001107240	23678889	23679340
ENSE00003563671	23687469	23687624
ENSE00003570218	23688668	23688745
ENSE00003579301	23680084	23680252
ENSE00003591629	23689238	23689392
ENSE00003596728	23689494	23689676
ENSE00003611528	23682064	23682157
ENSE00003663989	23680914	23681058
ENSE00003784817	23683870	23684089

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 97.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3058 / max 314.4776, expressed in 1464 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153165	44.2900	1453
153164	3.0158	933

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.18	gold quality
ganglionic eminence	UBERON:0004023	92.46	gold quality
mucosa of transverse colon	UBERON:0004991	90.36	gold quality
left testis	UBERON:0004533	90.28	gold quality
right testis	UBERON:0004534	89.43	gold quality
embryo	UBERON:0000922	89.30	gold quality
lower esophagus mucosa	UBERON:0035834	87.31	gold quality
testis	UBERON:0000473	87.11	gold quality
endometrium epithelium	UBERON:0004811	86.51	gold quality
stromal cell of endometrium	CL:0002255	85.77	gold quality
rectum	UBERON:0001052	83.13	gold quality
transverse colon	UBERON:0001157	82.05	gold quality
esophagus mucosa	UBERON:0002469	81.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.81	gold quality
secondary oocyte	CL:0000655	79.20	gold quality
lymph node	UBERON:0000029	79.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.09	gold quality
oocyte	CL:0000023	78.93	gold quality
body of stomach	UBERON:0001161	78.61	gold quality
vermiform appendix	UBERON:0001154	78.19	gold quality
small intestine	UBERON:0002108	76.81	gold quality
spleen	UBERON:0002106	76.60	gold quality
granulocyte	CL:0000094	76.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.17	gold quality
cerebellar hemisphere	UBERON:0002245	76.03	gold quality
bone marrow cell	CL:0002092	75.83	gold quality
cerebellar cortex	UBERON:0002129	75.76	gold quality
stomach	UBERON:0000945	75.63	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6142	yes	974.02
E-GEOD-99795	yes	598.43
E-HCAD-13	yes	19.87
E-MTAB-6911	no	992.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
STAT3	Activation

Upstream regulators (CollecTRI, top): E2F1, E2F2, E2F3, E2F4, FOXM1, FOXO1, MYBL2, NFKB, NFYA, PARP1, RELA, SMARCA1, STAT3, TP53, TP73, ZNF143

miRNA regulators (miRDB)

17 targeting PLK1, 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-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-1224-3P	97.24	65.92	851
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-6734-5P	95.70	65.56	950

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• We have observed that overexpression of the C-terminal domain of Plk is more effective than wild-type or kinase-defective Plk in causing mitotic delay or arrest. (PMID:11854496)
• results suggest that Plk1 phosphorylates Cdc25C on Ser198 and regulates nuclear translocation of Cdc25C during prophase (PMID:11897663)
• These results suggest that Polo-like kinase regulates the dissociation of cohesin from chromosomes early in mitosis. (cohesin) (PMID:11931760)
• both PB1 and PB2 regions are required for targeting the catalytic activity of Plk1 to centrosomes, midbody, and kinetochores (PMID:12034729)
• role of depletion in activating Cdc2/cyclin B and inhibition of centrosome amplification (PMID:12077309)
• Downregulation of cellular PLK1 levels in cancer cells altered cell cycle progression moderately with an elevated percentage (20-30%) of cells in G(2)/M. Furthermore, cells with reduced PLK1 protein gained a rounded phenotype with multiple centrosomes. (PMID:12082631)
• Plk1 kinase is involved in regulation of cyclin B1 phosphorylation and inhibited by ATR (PMID:12147700)
• Ser-137 may have an unexpected and novel role in the function of Plk (PMID:12207013)
• accumulates in both the nucleus and the cytoplasm in addition to its localization to the centrosome during S and G(2) phases (PMID:12364337)
• promoter elements responsible for transcriptional inhibition of polo-like kinase 1 and topoisomerase IIalpha genes by p21(WAF1/CIP1/SDI1) (PMID:12429910)
• A site corresponding to Ser326 in Plx1 was shown to be phosphorylated in the human polo-like kinase Plk1 (Ser335) (PMID:12442251)
• role in regulating subcellular localization of cyclin B1 (PMID:12447691)
• interaction with Chk2 and localization to centrosomes and midbody (PMID:12493754)
• Suppression of the activity of PLK1 via inhibition of tyrosine kinase activity by beta-HIVS might play a critical role in the induction of apoptosis. (PMID:12592388)
• identified the polo-box domain (PBD) of the mitotic kinase polo-like kinase 1 as a specific phosphoserine or phosphothreonine binding domain and determined its optimal binding motif (PMID:12595692)
• PLK1 overexpression was significantly associated with p53 accumulation in colorectal cancers. Our results suggest overexpression of PLK1 might be of pathogenic, prognostic and proliferative importance. (PMID:12708489)
• Depletion of this enzyme induces apoptosis in cancer cells (PMID:12732729)
• a consensus motif for Plk (Polo-like kinase) phosphorylation is identified, and Myt1 is a Plk1 substrate (PMID:12738781)
• Plk1 phosphorylates BRCA2 in M phase (PMID:12815053)
• PLK1 regulates Nlp, a centrosome protein involved in microtubule nucleation. (PMID:12852856)
• PLK1 phosphorylation of NudC plays an essential role in cytokinesis. (PMID:12852857)
• Data suggest that phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 (Plk1) is necessary for the restriction of Plk1 to the spindle during anaphase and telophase, and the complex of these two proteins is required for cytokinesis. (PMID:12939256)
• Data show that the Polo-box domains of human, Xenopus, and yeast polo-like kinases all recognize similar phosphoserine/threonine-containing motifs (PMID:14532005)
• crystal structure of Plk1 polo box domain provides an explanation for phospho-peptide recognition (PMID:14592974)
• Cell cycle arrest at G2/M after ionizing radiation (IR) of breast carcinoma cells may involve repression of the gene for Plk1. (PMID:14654792)
• A putative destruction box in Plk1 is required for degradation of Plk1 in anaphase. (PMID:14734534)
• PLK1 does not act as a cell cycle regulator but plays a constitutive role in papillary carcinoma especially in the early phase, and may contribute to the malignant transformation of this carcinoma (PMID:14735186)
• PLK1 regulates the cell cycle progression of thyroid lymphoma cells in the G2-M-phase. (PMID:15015605)
• p53 is a critical target of Plk1, and its function is abrogated through the physical interaction with Plk1. (PMID:15024021)
• Data demonstrate that Plk1 (Polo-like kinase 1) is a target of the retinoblastoma tumor suppressor (RB) pathway. (PMID:15105433)
• Mitotic phosphorylation of Nir2 is required for docking of the phospho-Ser/Thr binding module, the Polo box domain of Plk1, and overexpression of a Nir2 mutant, which fails to interact with Plk1, affects the completion of cytokinesis. (PMID:15125835)
• Antisense-treated pancreatic cancer cells showed cell cycle arrest in G(2)-M as well as a drastic reduction in proliferation rates (PMID:15141022)
• High rate of PLK-1 positivity seen in prostate cancer; PLK1 may be involved in prostate cancer tumorigenesis and progression (PMID:15176053)
• the role of Plk1 in mitosis regulation through the identification of Ser-4 in B23 nucleophosmin as a major physiological substrate of Plk1 (PMID:15190079)
• Plk1 and CHO1/MKLP-1 interact to have a role in cytokinesis (PMID:15199097)
• Plk1 has a role in bipolar spindle formation but is not necessary for APC/C-Cdc20 activation and initiation of cytokinesis (PMID:15210710)
• Treatment of mitotic cells with DNA damaging agents inhibits Plk1 activity primarily through dephosphorylation of Plk1. (PMID:15280449)
• The cell cycle machinery is reset in response to DNA damage and that cells become critically dependent on Plk1-mediated degradation of Wee1 for their recovery. (PMID:15350223)
• Plk-1 is required for proper spindle assembly and function. (PMID:15458642)
• Plk1 activates the anaphase promoting complex by directing the SCF-dependent destruction of Emi1 in prophase (PMID:15469984)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Plk1	ENSMUSG00000030867
rattus_norvegicus	Plk1	ENSRNOG00000018815
drosophila_melanogaster	polo	FBGN0003124

Paralogs (4): PLK4 (ENSG00000142731), PLK2 (ENSG00000145632), PLK3 (ENSG00000173846), PLK5 (ENSG00000185988)

Protein

Protein identifiers

Serine/threonine-protein kinase PLK1 — P53350 (reviewed: P53350)

Alternative names: Polo-like kinase 1, Serine/threonine-protein kinase 13

All UniProt accessions (4): P53350, I3L2H5, I3L309, I3L387

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning. Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage. Phosphorylates CEP68 and is required for its degradation. Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope. Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock. Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression. Regulates mitotic progression by phosphorylating RIOK2. Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis. Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites. Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10.

Subunit / interactions. Interacts with CEP170. Interacts with EVI5. Interacts with FAM29A. Interacts with SLX4/BTBD12. Interacts with TTDN1. Interacts (via POLO-box domain) with the phosphorylated form of BUB1, CDC25C and CENPU. Interacts with KIF2A. Interacts with CYLD. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with BIRC6/bruce. Interacts with CDK1-phosphorylated FRY; this interaction occurs in mitotic cells, but not in interphase cells. FRY interaction facilitates AURKA-mediated PLK1 phosphorylation. Interacts with CDK1-phosphorylated DCTN6 during mitotic prometaphase; the interaction facilitates recruitment to kinetochores. Interacts with CEP68; the interaction phosphorylates CEP68. Interacts (via POLO-box domain) with DCTN1. Interacts with CEP20 in later G1, S, G2 and M phases of the cell cycle; this interaction recruits PLK1 to centrosomes, a step required for S phase progression. Interacts with KLHL22. Interacts (via POLO box domains) with NEDD9/HEF1 (via C-terminus). Interacts with FIRRM (via N-terminus region); required for maintaining, but not activating, PLK1 kinase activity. Interacts with FZR1. Interacts with SKA3; the interaction promotes the stability of PLK1; the interaction promotes the stability of PLK1. Interacts with the MTMR3:MTMR4 heterooligomer; brings CEP55 and PLK1 together during early mitosis, regulating the phosphorylation of CEP55 by PLK1 and its recruitment to the midbody where it can mediate cell abscission.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Midbody.

Tissue specificity. Placenta and colon.

Post-translational modifications. Catalytic activity is enhanced by phosphorylation of Thr-210. Phosphorylation at Thr-210 is first detected on centrosomes in the G2 phase of the cell cycle, peaks in prometaphase and gradually disappears from centrosomes during anaphase. Dephosphorylation at Thr-210 at centrosomes is probably mediated by protein phosphatase 1C (PP1C), via interaction with PPP1R12A/MYPT1. Autophosphorylation and phosphorylation of Ser-137 may not be significant for the activation of PLK1 during mitosis, but may enhance catalytic activity during recovery after DNA damage checkpoint. Phosphorylated in vitro by STK10. Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in anaphase and following DNA damage, leading to its degradation by the proteasome. Ubiquitination is mediated via its interaction with FZR1/CDH1. Ubiquitination and subsequent degradation prevents entry into mitosis and is essential to maintain an efficient G2 DNA damage checkpoint. Monoubiquitination at Lys-492 by the BCR(KLHL22) ubiquitin ligase complex does not lead to degradation: it promotes PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation.

Disease relevance. Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cell lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis.

Activity regulation. Activated by phosphorylation of Thr-210 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1.

Domain organisation. The POLO box domains act as phosphopeptide-binding module that recognizes and binds serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. PLK1 can also create its own docking sites by mediating phosphorylation of serine-[phosphothreonine/phosphoserine]-(proline/X) motifs subsequently recognized by the POLO box domains.

Induction. By growth-stimulating agents.

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

RefSeq proteins (1): NP_005021* (*=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
IPR033702	PLK1_cat	Domain
IPR036947	POLO_box_dom_sf	Homologous_superfamily

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), 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 (127 total): strand 24, helix 22, mutagenesis site 20, modified residue 11, sequence conflict 11, turn 9, sequence variant 8, binding site 5, region of interest 5, domain 3, cross-link 3, compositionally biased region 2, initiator methionine 1, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4X9R	X-RAY DIFFRACTION	1.4
3P34	X-RAY DIFFRACTION	1.4
3Q1I	X-RAY DIFFRACTION	1.4
4X9V	X-RAY DIFFRACTION	1.43
4O6W	X-RAY DIFFRACTION	1.45
6AX4	X-RAY DIFFRACTION	1.45
3RQ7	X-RAY DIFFRACTION	1.55
4DFW	X-RAY DIFFRACTION	1.55
3FVH	X-RAY DIFFRACTION	1.58
4LKL	X-RAY DIFFRACTION	1.58
3P36	X-RAY DIFFRACTION	1.59
4RCP	X-RAY DIFFRACTION	1.6
9QMO	X-RAY DIFFRACTION	1.6
7MX1	X-RAY DIFFRACTION	1.64
8CRC	X-RAY DIFFRACTION	1.65
3P2W	X-RAY DIFFRACTION	1.66
4O9W	X-RAY DIFFRACTION	1.69
3HIH	X-RAY DIFFRACTION	1.7
4E9C	X-RAY DIFFRACTION	1.7
3HIK	X-RAY DIFFRACTION	1.77
5NN1	X-RAY DIFFRACTION	1.78
3P2Z	X-RAY DIFFRACTION	1.79
8JOQ	X-RAY DIFFRACTION	1.8
4X9W	X-RAY DIFFRACTION	1.8
4O56	X-RAY DIFFRACTION	1.8
4WHK	X-RAY DIFFRACTION	1.8
5NFU	X-RAY DIFFRACTION	1.81
5NN2	X-RAY DIFFRACTION	1.81
7MSO	X-RAY DIFFRACTION	1.85
1UMW	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53350-F1	85.11	0.67

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): 176 (proton acceptor)

Ligand- & substrate-binding residues (5): 59–67; 82; 131; 178–181; 194

Post-translational modifications (14): 2, 6, 103, 137, 210, 214, 269, 335, 375, 450, 498, 19, 338, 492

Mutagenesis-validated functional residues (20):

Position	Phenotype
67	in analog-sensitive mutant; enlarged catalytic pocket to accommodate purine analogs; when associated with g-130.
82	loss of kinase activity. no effect on s-phase progression.
82	loss of kinase activity. no effect on riok2-binding.
130	in analog-sensitive mutant; enlarged catalytic pocket to accommodate purine analogs; when associated with v-67.
137	no change in activity. increases activity and restores recovery after dna damage checkpoint; when associated with d-210.
137	increases activity. results in a block in g1/s.
176	abolishes kinase activity.
194	does not interfere with fry-binding.
210	abolishes activity. abolishes checkpoint recovery.
210	increases activity and restores recovery after dna damage checkpoint.
210	reduced catalytic activity, but no effect on affinity for atp.
337	interferes with ubiquitination and subsequent proteasomal degradation in anaphase; when associated with a-340.
340	interferes with ubiquitination and subsequent proteasomal degradation in anaphase; when associated with a-337.
414	abolishes interaction with cdc25c and reduces centrosomal localization.
414	no effect on centrosomal localization, nor on s-phase progression; when asscociated with a-427. loss of centrosomal loca
415	loss of centrosomal localization and of s-phase progression; when associated with a- 414 and a-427.
427	no effect on centrosomal localization, nor on s-phase progression; when associated with a-414. loss of centrosomal local
492	severe mitotic defects leading to prometaphase delay. increased localization at kinetochores leading to increased levels
538	in pincer mutant; loss of centrosomal location and decreased interaction with phosphorylated cdc25c and bub1; when assoc
540	in pincer mutant; loss of centrosomal location and decreased interaction with phosphorylated cdc25c and bub1; when assoc

Function

Pathways and Gene Ontology

Reactome pathways

25 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-156711	Polo-like kinase mediated events
R-HSA-162658	Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-176412	Phosphorylation of the APC/C
R-HSA-176417	Phosphorylation of Emi1
R-HSA-2299718	Condensation of Prophase Chromosomes
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-2980767	Activation of NIMA Kinases NEK9, NEK6, NEK7
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-68881	Mitotic Metaphase/Anaphase Transition
R-HSA-68884	Mitotic Telophase/Cytokinesis
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation

MSigDB gene sets: 593 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, MODULE_52, GOBP_REGULATION_OF_DNA_RECOMBINATION, HORIUCHI_WTAP_TARGETS_DN, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, MODULE_451, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, KANG_DOXORUBICIN_RESISTANCE_UP, MORF_ESPL1, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS

GO Biological Process (56): mitotic sister chromatid segregation (GO:0000070), G2/M transition of mitotic cell cycle (GO:0000086), negative regulation of transcription by RNA polymerase II (GO:0000122), mitotic cell cycle (GO:0000278), mitotic cytokinesis (GO:0000281), microtubule bundle formation (GO:0001578), double-strand break repair (GO:0006302), protein phosphorylation (GO:0006468), mitotic spindle organization (GO:0007052), sister chromatid cohesion (GO:0007062), mitotic chromosome condensation (GO:0007076), mitotic nuclear membrane disassembly (GO:0007077), metaphase/anaphase transition of mitotic cell cycle (GO:0007091), mitotic spindle assembly checkpoint signaling (GO:0007094), mitotic G2 DNA damage checkpoint signaling (GO:0007095), centrosome cycle (GO:0007098), regulation of mitotic cell cycle (GO:0007346), female meiosis chromosome segregation (GO:0016321), regulation of mitotic metaphase/anaphase transition (GO:0030071), astral microtubule organization (GO:0030953), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), regulation of cytokinesis (GO:0032465), negative regulation of apoptotic process (GO:0043066), homologous chromosome segregation (GO:0045143), establishment of protein localization (GO:0045184), positive regulation of mitotic metaphase/anaphase transition (GO:0045842), Golgi inheritance (GO:0048313), regulation of cell cycle (GO:0051726), synaptonemal complex disassembly (GO:0070194), protein localization to chromatin (GO:0071168), double-strand break repair via alternative nonhomologous end joining (GO:0097681), positive regulation of protein localization to nucleus (GO:1900182), regulation of mitotic spindle assembly (GO:1901673), regulation of mitotic cell cycle phase transition (GO:1901990), mitotic cleavage furrow formation (GO:1903673), regulation of protein localization to cell cortex (GO:1904776), positive regulation of mitotic nuclear envelope disassembly (GO:1905559), regulation of anaphase-promoting complex-dependent catabolic process (GO:1905784), negative regulation of double-strand break repair via homologous recombination (GO:2000042), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060)

GO Molecular Function (13): magnesium ion binding (GO:0000287), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), microtubule binding (GO:0008017), anaphase-promoting complex binding (GO:0010997), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (22): kinetochore (GO:0000776), chromatin (GO:0000785), synaptonemal complex (GO:0000795), spindle pole (GO:0000922), outer kinetochore (GO:0000940), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), spindle (GO:0005819), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), centriolar satellite (GO:0034451), spindle midzone (GO:0051233), mitotic spindle pole (GO:0097431), chromosome, centromeric region (GO:0000775), condensed chromosome, centromeric region (GO:0000779), chromosome (GO:0005694), cytoskeleton (GO:0005856), spindle microtubule (GO:0005876)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
G2/M Transition	2
Mitotic Prophase	2
Mitotic Prometaphase	2
Centrosome maturation	2
M Phase	2
Amplification of signal from the kinetochores	1
APC/C-mediated degradation of cell cycle proteins	1
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1
Regulation of APC/C activators between G1/S and early anaphase	1
Mitotic Anaphase	1
Nuclear Envelope Breakdown	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
Mitotic Metaphase and Anaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	8
cellular anatomical structure	8
mitotic cell cycle process	4
intracellular membraneless organelle	4
mitotic nuclear division	2
mitotic cell cycle phase transition	2
spindle organization	2
cell cycle process	2
protein kinase activity	2
spindle	2
microtubule organizing center	2
sister chromatid segregation	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
cell cycle	1
cytoskeleton-dependent cytokinesis	1
microtubule cytoskeleton organization	1
DNA repair	1
phosphorylation	1
protein modification process	1
microtubule cytoskeleton organization involved in mitosis	1
chromosome organization	1
mitotic sister chromatid segregation	1
chromosome condensation	1
nuclear membrane disassembly	1
metaphase/anaphase transition of cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
microtubule organizing center organization	1
regulation of cell cycle	1
female meiotic nuclear division	1
meiotic chromosome segregation	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1

Protein interactions and networks

STRING

5416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLK1	CCNB1	P14635	982
PLK1	CENPU	Q71F23	961
PLK1	CDC25C	P30307	951
PLK1	ERCC6L	Q2NKX8	948
PLK1	BUB1	O43683	937
PLK1	BUB1B	O60566	933
PLK1	TP53	P04637	930
PLK1	WEE1	P30291	926
PLK1	CDC20	Q12834	910
PLK1	ECT2	Q9H8V3	889
PLK1	CDCA8	Q53HL2	867
PLK1	NUDC	Q9Y266	867
PLK1	ESPL1	Q14674	854
PLK1	CCNB2	O95067	844
PLK1	HSP90AB1	P08238	842

IntAct

427 interactions, top by confidence:

A	B	Type	Score
PLK1	CDC25C	psi-mi:“MI:0407”(direct interaction)	0.860
PLK1	CDC25C	psi-mi:“MI:0915”(physical association)	0.860
PLK1	BORA	psi-mi:“MI:0915”(physical association)	0.850
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
PLK1	PLK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.800
PLK1	SPAG9	psi-mi:“MI:0914”(association)	0.790
PLK1	ERCC6L	psi-mi:“MI:0914”(association)	0.790
ERCC6L	PLK1	psi-mi:“MI:0914”(association)	0.790
PLK1	SLX4	psi-mi:“MI:0915”(physical association)	0.780
SLX4	PLK1	psi-mi:“MI:0915”(physical association)	0.780
PLK1	SLX4	psi-mi:“MI:0914”(association)	0.780
ERCC4	PLK1	psi-mi:“MI:0914”(association)	0.770
PLK1	ERCC4	psi-mi:“MI:0915”(physical association)	0.770
FOXJ1	RFX3	psi-mi:“MI:0914”(association)	0.730
PLK1	CHEK2	psi-mi:“MI:0915”(physical association)	0.720
PLK1	CHEK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
CHEK2	PLK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
PLK1	CHEK2	psi-mi:“MI:0403”(colocalization)	0.720
TP53BP1	PLK1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (1487): PLK1 (Affinity Capture-Western), PLK1 (Affinity Capture-Western), RAP1GAP (Affinity Capture-Western), RAP1GAP (Biochemical Activity), PLK1 (Affinity Capture-Western), BRCA2 (Biochemical Activity), PLK1 (Affinity Capture-Western), PLK1 (Biochemical Activity), PLK1 (Affinity Capture-Western), CDC14A (Biochemical Activity), SLX4 (Affinity Capture-MS), Sugt1 (Biochemical Activity), PLK1 (Affinity Capture-MS), PLK1 (Affinity Capture-MS), PLK1 (Affinity Capture-MS)

ESM2 similar proteins: A2AHJ4, A2AQW0, A7MBL8, A9JRL3, F1ND48, O00418, O08796, O08874, O35099, P15056, P28028, P32866, P34908, P53350, P53351, P62205, P70032, P70531, Q07832, Q16513, Q21029, Q2TA25, Q3TWN3, Q4U2V3, Q5E9N5, Q5R4L1, Q5R9R1, Q5ZKK7, Q62673, Q641K1, Q6DD21, Q6RI45, Q6ZN16, Q80V94, Q8AYK6, Q8BPM2, Q8IVH8, Q8QGV2, Q921C3, Q99683

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

200 interactions.

A	Effect	B	Mechanism
PLK1	“down-regulates activity”	BRCA2	phosphorylation
PLK1	“up-regulates activity”	NUDC	phosphorylation
PLK1	“up-regulates activity”	CCNB1	phosphorylation
PLK1	up-regulates	CDC25C	phosphorylation
PLK1	up-regulates	ANAPC1	phosphorylation
PLK1	down-regulates	WEE1	phosphorylation
PLK1	up-regulates	NPM1	phosphorylation
PLK1	down-regulates	FBXO5	phosphorylation
PLK1	“down-regulates activity”	IRS1	phosphorylation
PLK1	up-regulates	PIN1	phosphorylation
PLK1	up-regulates	CEP55	phosphorylation
EVI5	down-regulates	PLK1
BUB1	up-regulates	PLK1	binding
PLK1	down-regulates	CLSPN	phosphorylation
PLK1	up-regulates	RAN	phosphorylation
PLK1	up-regulates	KIZ	phosphorylation
PLK1	down-regulates	CENPU	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 153 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of ATR in response to replication stress	6	16.9×	7e-05
AURKA Activation by TPX2	11	15.7×	3e-08
Regulation of PLK1 Activity at G2/M Transition	13	15.4×	1e-09
Loss of Nlp from mitotic centrosomes	10	14.8×	2e-07
Loss of proteins required for interphase microtubule organization from the centrosome	10	14.8×	2e-07
Homology Directed Repair	5	14.4×	7e-04
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	14.4×	7e-04
Resolution of D-loop Structures through Holliday Junction Intermediates	5	14.0×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of fibroblast proliferation	5	11.0×	7e-03
DNA replication	7	8.6×	2e-03
double-strand break repair via homologous recombination	7	8.2×	3e-03
DNA repair	15	7.2×	2e-06
cell division	19	6.5×	1e-07
cell population proliferation	8	6.1×	4e-03
cilium assembly	10	5.5×	2e-03
DNA damage response	11	4.4×	4e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	62
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3243354	NC_000016.9:g.(?23647371)(23700359_?)del	Pathogenic

SpliceAI

1385 predictions. Top by Δscore:

Variant	Effect	Δscore
16:23680076:A:AG	acceptor_gain	1.0000
16:23680080:A:AG	acceptor_gain	1.0000
16:23680081:C:G	acceptor_gain	1.0000
16:23680081:CAGTC:C	acceptor_loss	1.0000
16:23680082:A:AG	acceptor_gain	1.0000
16:23680082:A:C	acceptor_loss	1.0000
16:23680083:G:GG	acceptor_gain	1.0000
16:23680083:GT:G	acceptor_gain	1.0000
16:23680083:GTC:G	acceptor_gain	1.0000
16:23680083:GTCT:G	acceptor_gain	1.0000
16:23680083:GTCTC:G	acceptor_gain	1.0000
16:23680252:GGT:G	donor_loss	1.0000
16:23680253:G:GG	donor_gain	1.0000
16:23680253:GTG:G	donor_loss	1.0000
16:23680254:T:G	donor_loss	1.0000
16:23680912:A:AG	acceptor_gain	1.0000
16:23680912:AG:A	acceptor_gain	1.0000
16:23680912:AGG:A	acceptor_gain	1.0000
16:23680912:AGGG:A	acceptor_gain	1.0000
16:23680913:G:GG	acceptor_gain	1.0000
16:23680913:GG:G	acceptor_gain	1.0000
16:23680913:GGG:G	acceptor_gain	1.0000
16:23680913:GGGG:G	acceptor_gain	1.0000
16:23683865:CCCA:C	acceptor_loss	1.0000
16:23683866:CCAGC:C	acceptor_loss	1.0000
16:23683867:CAGCA:C	acceptor_loss	1.0000
16:23683868:A:AG	acceptor_gain	1.0000
16:23683868:AGCAC:A	acceptor_loss	1.0000
16:23683869:G:GG	acceptor_gain	1.0000
16:23683869:GC:G	acceptor_gain	1.0000

AlphaMissense

3944 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:23679116:G:C	G62R	1.000
16:23679116:G:T	G62C	1.000
16:23679122:T:A	F64I	1.000
16:23679122:T:C	F64L	1.000
16:23679122:T:G	F64V	1.000
16:23679123:T:C	F64S	1.000
16:23679123:T:G	F64C	1.000
16:23679124:T:A	F64L	1.000
16:23679124:T:G	F64L	1.000
16:23679126:C:A	A65D	1.000
16:23679133:C:G	C67W	1.000
16:23679176:A:C	K82Q	1.000
16:23679178:G:C	K82N	1.000
16:23679178:G:T	K82N	1.000
16:23679331:C:G	C133W	1.000
16:23680109:G:T	R145M	1.000
16:23680199:G:C	R175P	1.000
16:23680201:G:C	D176H	1.000
16:23680202:A:C	D176A	1.000
16:23680202:A:G	D176G	1.000
16:23680202:A:T	D176V	1.000
16:23680203:C:A	D176E	1.000
16:23680203:C:G	D176E	1.000
16:23680209:G:C	K178N	1.000
16:23680209:G:T	K178N	1.000
16:23680216:A:G	N181D	1.000
16:23680218:C:A	N181K	1.000
16:23680218:C:G	N181K	1.000
16:23680252:G:T	G193W	1.000
16:23680914:G:A	G193E	1.000

dbSNP variants (sampled 300 via entrez): RS1000208585 (16:23681487 A>G), RS1000460948 (16:23686549 G>A), RS1000732172 (16:23679670 G>C,T), RS1001713678 (16:23681757 C>T), RS1001786022 (16:23681581 C>G), RS1001823826 (16:23688301 T>G), RS1002625501 (16:23682979 C>A,T), RS1002716527 (16:23683440 A>G), RS1003343378 (16:23684674 T>G), RS1003713795 (16:23684802 C>T), RS1003810627 (16:23682729 A>C,G), RS1004008876 (16:23677710 C>A,T), RS1004032626 (16:23684386 T>C), RS1004484952 (16:23677410 T>C), RS1004693576 (16:23686963 G>A)

Disease associations

OMIM: gene MIM:602098 | disease phenotypes: MIM:601675, MIM:114480

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive

Mondo (3): trichothiodystrophy (MONDO:0018053), hereditary breast carcinoma (MONDO:0016419), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Trichothiodystrophy (Orphanet:33364), Hereditary breast cancer (Orphanet:227535)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002392_497	Mean corpuscular volume	3.000000e-09
GCST90002396_581	Mean reticulocyte volume	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3024 (SINGLE PROTEIN), CHEMBL4742280 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195529 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

25 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 195,574 (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
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL1233528	VOLASERTIB	3	1,511
CHEMBL1241855	RIGOSERTIB	3	1,544
CHEMBL2013119	RIGOSERTIB SODIUM	3	1,001
CHEMBL50	QUERCETIN	3	74,559
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1672002	THYMOQUINONE	2	1,497
CHEMBL1738758	ONVANSERTIB	2	780
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL2165191	AZD-6482	2	912
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL8260	BAICALEIN	2
CHEMBL1908394	GSK-461364	1
CHEMBL1980391	RG-1530	1
CHEMBL2392545	TAK-960	1
CHEMBL259084	MLN-8054	1

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 (14 total), top 14:

Ligand	Action	Affinity	Parameter
Ro3280	Inhibition	10.05	pKd
GSK-461364A	Inhibition	9.3	pKi
volasertib	Inhibition	9.06	pIC50
onvansertib	Inhibition	8.7	pIC50
GSK579289A	Inhibition	8.7	pIC50
compound 2 [PMID: 19097784]	Inhibition	8.7	pIC50
MLN0905	Inhibition	8.7	pIC50
BI-2536	Inhibition	8.52	pKi
GW853606	Inhibition	8.05	pIC50
compound 6 [PMID: 30125504]	Inhibition	8.0	pIC50
WNY0824	Inhibition	7.66	pIC50
dual BRD4/PLK1 inhibitor 23	Inhibition	7.4	pIC50
plogosertib	Inhibition	7.0	pIC50
XY-06-007	Inhibition	6.01	pIC50

Binding affinities (BindingDB)

194 measured of 392 human assays (402 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[(9-cyclopentyl-5-methyl-6-oxo-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	KD	0.57 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
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
1-methyl-8-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide	IC50	1 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
8-(5-(piperazin-1-yl)-2-(trifluoromethoxy)phenylamino)-1-vinyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide	IC50	1 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
Staurosporine	KD	1.7 nM
BMCL191018 Compound 2	IC50	2 nM
5-(6-methoxy-1H-1,3-benzodiazol-1-yl)-3-{[2-(trifluoromethyl)phenyl]methoxy}thiophene-2-carboxamide	IC50	2 nM
3-[(2-bromophenyl)methoxy]-5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	2 nM
3-[(2-chlorophenyl)methoxy]-5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	2 nM
3-[(3-chlorothiophen-2-yl)methoxy]-5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	2 nM
5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)-3-{[2-(trifluoromethyl)phenyl]methoxy}thiophene-2-carboxylic acid	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
1-methyl-8-(5-(piperazin-1-yl)-2-(trifluoromethoxy)phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide	IC50	2 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
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
1-(2-HYDROXYETHYL)-8-[[5-(4-METHYLPIPERAZIN-1-YL)-2-(TRIFLUOROMETHOXY)PHENYL]AMINO]-4,5-DIHYDROPYRIMIDO[5,4-G]INDAZOLE-3-CARBOXAMIDE	IC50	3 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
(3R,4R)-3-methoxy-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	3.93 nM	US-10189849: CDK inhibitors
5-(6-chloro-1H-1,3-benzodiazol-1-yl)-3-[(2-methylphenyl)methoxy]thiophene-2-carboxamide	IC50	4 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
5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)-3-{[2-(trifluoromethoxy)phenyl]methoxy}thiophene-2-carboxamide	IC50	5 nM
1-methyl-8-[2-methyl-5-(4-methylpiperazin-1-yl)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxylate	IC50	5 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
1-(2-fluoroethyl)-8-(5-(piperazin-1-yl)-2-(trifluoromethoxy)phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide	IC50	5 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
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-[(2-cyanophenyl)methoxy]-5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)thiophene-2-carboxamide	IC50	6 nM
5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)-3-{[2-(trifluoromethyl)phenyl]methoxy}thiophene-2-carbothioamide	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
8-[5-(hydroxymethyl)-2-methoxyanilino]-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	IC50	7 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
9-cyclopentyl-2-[4-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methoxyanilino]-5-methyl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one	KD	8 nM	US-9266890: Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
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
5-(5-methoxy-1H-1,3-benzodiazol-1-yl)-3-{[2-(trifluoromethyl)phenyl]methoxy}thiophene-2-carboxamide	IC50	8 nM
5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)-3-[(2-methoxyphenyl)methoxy]thiophene-2-carboxamide	IC50	8 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	8 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
3-[(2-bromophenyl)methoxy]-5-[6-(trifluoromethyl)-1H-1,3-benzodiazol-1-yl]thiophene-2-carboxamide	IC50	9 nM
Rigosertib sodium	IC50	9 nM
1-methyl-8-[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)anilino]-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxylate	IC50	10 nM	US-8614220: Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
8-[2-methoxy-5-(4-methylpiperazin-1-yl)anilino]-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide	IC50	10 nM	US-8614220: Substituted pyrazolo-quinazoline 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
5-(1H-1,3-benzodiazol-1-yl)-3-[(2-bromophenyl)methoxy]thiophene-2-carboxamide	IC50	11 nM
5-(5,6-dimethoxy-1H-1,3-benzodiazol-1-yl)-3-(thiophen-2-ylmethoxy)thiophene-2-carboxamide	IC50	11 nM
5-(1H-1,3-benzodiazol-1-yl)-3-[(2-methylphenyl)methoxy]thiophene-2-carboxamide	IC50	12 nM

ChEMBL bioactivities

1611 potent at pChembl≥5 of 1823 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.08	IC50	0.083	nM	BI-2536
10.03	Kd	0.094	nM	GSK-461364
9.92	IC50	0.12	nM	CHEMBL6145835
9.89	IC50	0.13	nM	CHEMBL6145038
9.82	IC50	0.15	nM	CHEMBL6159528
9.77	IC50	0.17	nM	CHEMBL5417495
9.74	IC50	0.18	nM	CHEMBL5423881
9.72	Kd	0.19	nM	BI-2536
9.72	Kd	0.19	nM	CHEMBL4449858
9.72	IC50	0.19	nM	CHEMBL5419732
9.72	IC50	0.19	nM	CHEMBL6168202
9.70	EC50	0.2	nM	CHEMBL1625188
9.70	IC50	0.2	nM	CHEMBL5416208
9.68	IC50	0.21	nM	CHEMBL6152272
9.66	Ki	0.22	nM	BI-2536
9.64	IC50	0.23	nM	CHEMBL5438707
9.64	IC50	0.23	nM	CHEMBL5433401
9.59	IC50	0.26	nM	CHEMBL5415945
9.57	IC50	0.27	nM	CHEMBL6168713
9.57	IC50	0.27	nM	CHEMBL6173341
9.55	IC50	0.28	nM	CHEMBL6165777
9.52	IC50	0.3	nM	CHEMBL5426964
9.52	IC50	0.3	nM	CHEMBL5419367
9.52	IC50	0.3	nM	CHEMBL5429440
9.52	IC50	0.3	nM	CHEMBL5422122
9.52	IC50	0.3	nM	CHEMBL5421113
9.51	IC50	0.31	nM	CHEMBL6149970
9.49	IC50	0.32	nM	CHEMBL5435085
9.49	IC50	0.32	nM	CHEMBL6172114
9.48	IC50	0.33	nM	CHEMBL5429110
9.48	IC50	0.33	nM	CHEMBL6134427
9.47	IC50	0.34	nM	CHEMBL5438696
9.47	IC50	0.34	nM	CHEMBL6176603
9.47	IC50	0.34	nM	CHEMBL6133790
9.47	IC50	0.34	nM	CHEMBL6170664
9.46	IC50	0.35	nM	CHEMBL6163361
9.46	IC50	0.35	nM	CHEMBL6166604
9.46	IC50	0.35	nM	CHEMBL6168781
9.43	IC50	0.37	nM	CHEMBL5398211
9.42	IC50	0.38	nM	CHEMBL6142292
9.41	IC50	0.39	nM	CHEMBL5396078
9.41	IC50	0.39	nM	CHEMBL6167292
9.40	IC50	0.4	nM	CHEMBL4067710
9.40	IC50	0.4	nM	CHEMBL5427957
9.40	IC50	0.4	nM	CHEMBL5437785
9.39	IC50	0.41	nM	CHEMBL6175691
9.39	IC50	0.41	nM	CHEMBL6168752
9.38	Ki	0.42	nM	CHEMBL3609305
9.38	IC50	0.42	nM	CHEMBL5403473
9.38	IC50	0.42	nM	CHEMBL5426743

PubChem BioAssay actives

1442 with measured affinity, of 5055 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	1876145: Inhibition of PLK1 (unknown origin)	ic50	0.0001	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	624975: Binding constant for PLK1 kinase domain	kd	0.0001	uM
(7R)-2-[2-ethoxy-4-(1-methylpiperidin-4-yl)anilino]-7-ethyl-5-methyl-8-[(4-methylthiophen-2-yl)methyl]-7H-pteridin-6-one	1602828: Binding affinity to PLK1 (unknown origin)	kd	0.0002	uM
(7R)-8-cyclopentyl-7-ethyl-2-[4-[5-[(4-hydroxypiperidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl]-2-methoxyanilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0002	uM
(7R)-8-cyclopentyl-2-[4-[5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0002	uM
(7R)-8-cyclopentyl-2-[[1-[2-(cyclopentylamino)acetyl]-6-methoxy-2,3-dihydroindol-5-yl]amino]-7-ethyl-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0002	uM
(7R)-8-cyclohexyl-7-ethyl-2-[[6-methoxy-1-(2-morpholin-4-ylacetyl)-2,3-dihydroindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0002	uM
(7R)-2-[4-[5-[(cyclobutylamino)methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-8-cyclopentyl-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0002	uM
(7R)-8-cyclopentyl-7-ethyl-2-[4-[5-[[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0002	uM
N-[[4-[(6-chloro-3-pyridinyl)methoxy]-3-methoxyphenyl]methyl]-2-(3,4-dimethoxyphenyl)ethanamine	1874264: Inhibition of PLK1 in thymidine synchronized human HeLa cells using casein as substrate preincubated with compound for 13 hrs followed by substrate addition and measured after 12 to 36 hrs in the presence of [gamma33P]ATP by autoradiography based Western blot analysis	ec50	0.0002	uM
(7R)-8-cyclopentyl-2-[[1-[2-[(3S,5R)-3,5-dimethylpiperazin-1-yl]acetyl]-6-methoxy-2,3-dihydroindol-5-yl]amino]-7-ethyl-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0003	uM
(7R)-8-cyclopentyl-7-ethyl-2-[4-[5-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-1,2,4-oxadiazol-3-yl]-2-methoxyanilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0003	uM
(7R)-8-cyclopentyl-7-ethyl-2-[2-methoxy-4-[5-[[(1-methylpiperidin-4-yl)amino]methyl]-1,3,4-oxadiazol-2-yl]anilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0003	uM
(7R)-8-cyclopentyl-2-[[1-[2-(cyclopropylamino)acetyl]-6-methoxy-2,3-dihydroindol-5-yl]amino]-7-ethyl-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0003	uM
(7R)-8-cyclopentyl-7-ethyl-2-[[6-methoxy-1-[2-(4-methylpiperazin-1-yl)acetyl]-2,3-dihydroindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0003	uM
(7R)-8-cyclopentyl-7-ethyl-2-[2-methoxy-4-[5-(piperazin-1-ylmethyl)-1,3,4-oxadiazol-2-yl]anilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0003	uM
(7R)-8-cyclopentyl-7-ethyl-2-[[6-methoxy-1-(2-piperidin-1-ylacetyl)-2,3-dihydroindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0003	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	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0003	uM
(7R)-8-cyclopentyl-2-[4-[5-[(4-cyclopentylpiperazin-1-yl)methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0003	uM
4-[[(6R)-7-cyano-6-ethyl-5-propan-2-yl-6H-imidazo[1,5-f]pteridin-3-yl]amino]-N-(1-ethylpiperidin-4-yl)-2-fluoro-5-methoxybenzamide	1430209: Inhibition of human FLAG-tagged PLK1 expressed in baculovirus infected sf21 cells using Biotin-AGAGTVPESIHSFIGDGLV as substrate by TR-FRET assay	ic50	0.0004	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	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-2-[4-[5-[[(3S,5R)-3,5-dimethylpiperazin-1-yl]methyl]-1,2,4-oxadiazol-3-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-2-[4-[5-(1,4-diazepan-1-ylmethyl)-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-2-[4-[5-[(cyclopropylmethylamino)methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0004	uM
(7R)-2-[[1-[2-(4-acetylpiperazin-1-yl)acetyl]-6-methoxy-2,3-dihydroindol-5-yl]amino]-8-cyclohexyl-7-ethyl-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-7-ethyl-2-[4-[5-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-7-ethyl-2-[(6-methoxy-1-oxo-2-propan-2-yl-3H-isoindol-5-yl)amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-7-ethyl-2-[2-methoxy-4-[5-(morpholin-4-ylmethyl)-1,3,4-oxadiazol-2-yl]anilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-7-ethyl-2-[[1-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]acetyl]-6-methoxy-2,3-dihydroindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0004	uM
(7R)-8-cyclopentyl-2-[4-[5-[(cyclopentylamino)methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0004	uM
4-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	1242388: Binding affinity to PLK1 (unknown origin) expressed in HEK293 cells after 1 hr by proprietary competition assay	ki	0.0004	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-methoxy-N-(1-methylpiperidin-4-yl)benzamide	1242388: Binding affinity to PLK1 (unknown origin) expressed in HEK293 cells after 1 hr by proprietary competition assay	ki	0.0005	uM
methyl 2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-5-nitropyrimidin-4-yl]amino]benzoate	1742537: Inhibition of human PLK1 using casein as substrate in presence of [gamma-33P]ATP by radiometric assay	ic50	0.0005	uM
methyl 3-[[2-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-nitropyrimidin-4-yl]amino]thiophene-2-carboxylate	1742537: Inhibition of human PLK1 using casein as substrate in presence of [gamma-33P]ATP by radiometric assay	ic50	0.0005	uM
methyl 3-[[2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]-5-nitropyrimidin-4-yl]amino]thiophene-2-carboxylate	1742537: Inhibition of human PLK1 using casein as substrate in presence of [gamma-33P]ATP by radiometric assay	ic50	0.0005	uM
methyl 2-[[2-[2-methoxy-4-(4-pyrrolidin-1-ylpiperidin-1-yl)anilino]-5-nitropyrimidin-4-yl]amino]benzoate	1742537: Inhibition of human PLK1 using casein as substrate in presence of [gamma-33P]ATP by radiometric assay	ic50	0.0005	uM
methyl 3-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]thiophene-2-carboxylate	1742537: Inhibition of human PLK1 using casein as substrate in presence of [gamma-33P]ATP by radiometric assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-7-ethyl-2-[[6-methoxy-1-[2-(4-methylsulfonylpiperazin-1-yl)acetyl]-2,3-dihydroindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-7-ethyl-2-[[6-methoxy-1-(2-pyrrolidin-1-ylacetyl)-2,3-dihydroindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-2-[[1-[2-(1,1-dioxo-1,4-thiazinan-4-yl)acetyl]-6-methoxy-2,3-dihydroindol-5-yl]amino]-7-ethyl-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-2-[(2-cyclopentyl-6-methoxy-1-oxo-3H-isoindol-5-yl)amino]-7-ethyl-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-2-[4-[5-[[4-(cyclopropylmethyl)piperazin-1-yl]methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-7-ethyl-2-[[6-methoxy-1-(2-morpholin-4-ylacetyl)-2,3-dihydroindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-7-ethyl-2-[[6-methoxy-2-(1-methylpiperidin-4-yl)-1-oxo-3H-isoindol-5-yl]amino]-5-methyl-7H-pteridin-6-one	1984750: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-7-ethyl-2-[4-[5-[[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-1,2,4-oxadiazol-3-yl]-2-methoxyanilino]-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-2-[4-[5-[[2-(dimethylamino)ethyl-methylamino]methyl]-1,2,4-oxadiazol-3-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-2-[4-[5-[(cyclopropylamino)methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0005	uM
(7R)-8-cyclopentyl-2-[4-[5-[[(3R,5S)-3,5-dimethylpiperazin-1-yl]methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0005	uM
methyl 2-[[2-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyanilino]-5-nitropyrimidin-4-yl]amino]benzoate	1742537: Inhibition of human PLK1 using casein as substrate in presence of [gamma-33P]ATP by radiometric assay	ic50	0.0006	uM
(7R)-8-cyclopentyl-2-[4-[5-[[2-(dimethylamino)ethyl-methylamino]methyl]-1,3,4-oxadiazol-2-yl]-2-methoxyanilino]-7-ethyl-5-methyl-7H-pteridin-6-one	2007941: Inhibition of PLK1 (unknown origin) preincubated for 10 mins followed by substrate addition measured after 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	8
bisphenol A	increases expression, affects expression, decreases expression, affects localization	5
sodium arsenite	decreases expression, increases expression	5
Cisplatin	decreases reaction, increases activity, decreases response to substance, decreases expression, increases expression (+2 more)	4
Cyclosporine	decreases expression	4
ON 01910	decreases activity, decreases phosphorylation, affects response to substance, increases reaction	3
Doxorubicin	affects cotreatment, affects expression, affects phosphorylation, affects reaction, decreases expression	3
Tretinoin	decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
lasiocarpine	decreases expression, increases metabolic processing, affects cotreatment, affects expression	2
methylselenic acid	decreases expression, affects expression	2
cobaltous chloride	decreases expression	2
palbociclib	affects reaction, affects binding, decreases reaction, decreases expression	2
BI 2536	increases phosphorylation, decreases activity, decreases reaction	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Fulvestrant	decreases reaction, increases expression, affects binding, increases reaction	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Cadmium	decreases expression, increases abundance	2
Copper	decreases expression, affects binding	2
Coumestrol	affects cotreatment, increases expression, affects reaction	2
Fluorouracil	decreases expression, increases expression, affects reaction, decreases reaction	2
Oxygen	decreases expression	2
Quercetin	increases expression, decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression	2
Particulate Matter	increases abundance, decreases expression	2
RO3280	decreases reaction, increases phosphorylation	1
NVP-BHG712	affects cotreatment, decreases expression, increases reaction	1

ChEMBL screening assays

979 unique, capped per target: 967 binding, 8 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001555	Binding	Inhibition of okadaic acid activated PLK1 at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1963829	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PLK1	PubChem BioAssay data set
CHEMBL4018866	ADMET	Inhibition of PLK1 in HEK293T cells assessed as decrease in TCTP phosphorylation after 6 hrs by Western blot method	Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice