PLK4

Summary

PLK4 (polo like kinase 4, HGNC:11397) is a protein-coding gene on chromosome 4q28.1, encoding Serine/threonine-protein kinase PLK4 (O00444). Serine/threonine-protein kinase that plays a central role in centriole duplication. It is a common-essential gene (DepMap: required in 95.4% of cancer cell lines).

This gene encodes a member of the polo family of serine/threonine protein kinases. The protein localizes to centrioles, complex microtubule-based structures found in centrosomes, and regulates centriole duplication during the cell cycle. Three alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.

Source: NCBI Gene 10733 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly and chorioretinopathy 2 (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 713 total — 23 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes — 65 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 95.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_014264

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11397
Approved symbol	PLK4
Name	polo like kinase 4
Location	4q28.1
Locus type	gene with protein product
Status	Approved
Aliases	Sak
Ensembl gene	ENSG00000142731
Ensembl biotype	protein_coding
OMIM	605031
Entrez	10733

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000270861, ENST00000503914, ENST00000507249, ENST00000507454, ENST00000508113, ENST00000510192, ENST00000510605, ENST00000511942, ENST00000513090, ENST00000514379, ENST00000515069, ENST00000852980

RefSeq mRNA: 3 — MANE Select: NM_014264 NM_001190799, NM_001190801, NM_014264

CCDS: CCDS3735, CCDS54803, CCDS54804

Canonical transcript exons

ENST00000270861 — 16 exons

Exon	Start	End
ENSE00000956077	127883262	127883357
ENSE00000956078	127883439	127883553
ENSE00000956079	127885708	127886728
ENSE00000956080	127887396	127887496
ENSE00000956082	127891092	127891196
ENSE00000956084	127892365	127892514
ENSE00000956085	127893285	127893418
ENSE00001280184	127898439	127899224
ENSE00002068636	127880893	127881164
ENSE00003483918	127893734	127893881
ENSE00003518610	127893513	127893604
ENSE00003599372	127891579	127891681
ENSE00003608012	127896801	127896907
ENSE00003630062	127894953	127895093
ENSE00003656252	127881831	127881926
ENSE00003668667	127889866	127890236

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 96.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7695 / max 133.3829, expressed in 1309 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49607	6.6563	1304
49608	0.1131	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.71	gold quality
ganglionic eminence	UBERON:0004023	91.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.42	gold quality
sperm	CL:0000019	89.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.79	gold quality
embryo	UBERON:0000922	87.51	gold quality
male germ cell	CL:0000015	87.05	gold quality
left testis	UBERON:0004533	86.99	gold quality
testis	UBERON:0000473	86.83	gold quality
right testis	UBERON:0004534	86.45	gold quality
bone marrow	UBERON:0002371	84.39	gold quality
bone marrow cell	CL:0002092	82.73	gold quality
rectum	UBERON:0001052	82.34	gold quality
endometrium epithelium	UBERON:0004811	80.11	gold quality
vermiform appendix	UBERON:0001154	78.29	gold quality
mucosa of transverse colon	UBERON:0004991	78.14	gold quality
stromal cell of endometrium	CL:0002255	77.98	gold quality
lower esophagus mucosa	UBERON:0035834	77.35	gold quality
esophagus mucosa	UBERON:0002469	77.17	gold quality
adrenal tissue	UBERON:0018303	76.76	gold quality
cortical plate	UBERON:0005343	75.89	gold quality
trabecular bone tissue	UBERON:0002483	75.79	gold quality
secondary oocyte	CL:0000655	75.59	gold quality
lymph node	UBERON:0000029	75.44	gold quality
skin of abdomen	UBERON:0001416	72.91	gold quality
endometrium	UBERON:0001295	72.65	gold quality
pancreatic ductal cell	CL:0002079	72.08	silver quality
skin of leg	UBERON:0001511	72.01	gold quality
caecum	UBERON:0001153	71.75	gold quality
diaphragm	UBERON:0001103	71.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, E2F1, E2F2, E2F3, E2F4, KCNIP3, NFKB, SP1, TP53

miRNA regulators (miRDB)

53 targeting PLK4, 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-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-3942-3P	99.57	69.03	2854

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• SAK repression by p53 is likely mediated through the recruitment of HDAC repressors, and SAK repression contributes to p53-induced apoptosis (PMID:15967108)
• we identify Plk4 as a key regulator of centriole duplication.These findings provide an attractive explanation for the crucial function of Plk4 in cell proliferation and have implications for the role of Polo kinases in tumorigenesis. (PMID:16244668)
• SAK/PLK4 is required for centriole duplication and flagella development in Drosophila and human cells. (PMID:16326102)
• Overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole. (PMID:17681131)
• Human Plk4 phosphorylates Cdc25C. (PMID:18239451)
• Plk2 mediated centriole duplication is dependent on Plk4 function (PMID:19001868)
• HCT116 cells fail to organize the ninefold symmetry of centrioles due to insufficient Plk4. (PMID:19454482)
• CUL1 may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles. (PMID:19679553)
• Data suggest that polo-like kinase 4 activity is restricted to the centrosome to prevent aberrant centriole assembly and sustained kinase activity is required for centriole duplication. (PMID:20032307)
• Plk4 is required for cytokinesis and maintenance of chromosomal stability (PMID:20348415)
• Data suggest that active Plk4 promotes its own degradation by catalyzing betaTrCP binding through trans-autophosphorylation (phosphorylation by the other kinase in the dimer) within homodimers. (PMID:20516151)
• Results suggest that Cep152 recruits Plk4 and CPAP to the centrosome to ensure a faithful centrosome duplication process. (PMID:21059844)
• Data show that Cep152 can be phosphorylated by Plk4 in vitro, suggesting that Cep152 acts with Plk4 to initiate centriole formation. (PMID:21059850)
• CDK11(p58), which accumulates only in the vicinity of mitotic centrosomes, directly interacts with the centriole-associated protein kinase Plk4 that regulates centriole number in cells. (PMID:21297952)
• These results highlight the critical role of PLK4 transcriptional deregulation in centriole multiplication in HPV-16 E7-expressing cells. (PMID:21609466)
• The activity of SCF-FBXW5 is negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6. (PMID:21725316)
• STIL cooperates with SAS-6 and PLK4 in the control of centriole number and represents a key centriole duplication factor in human cells. (PMID:22349698)
• Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis. (PMID:22456511)
• Study demonstrated that PLK4 was remarkably downregulated in HCC and could be served as a potential prognostic marker for patients with this deadly disease. (PMID:22829937)
• CAND1 promotes PLK4-mediated centriole overduplication and is frequently disrupted in prostate cancer. (PMID:23019411)
• Preventing Plk4 autoregulation causes centrosome amplification, stabilization of p53, and loss of cell proliferation (PMID:23249732)
• cooperation between Cep192 and Cep152 is crucial for centriole recruitment of Plk4 and centriole duplication during the cell cycle. (PMID:23641073)
• If both p53 and the SAPKK MKK4 are simultaneously inactivated, persistent polo-like kinase 4 activity combined with the lack of SAPK-mediated inhibition of centrosome duplication conspire to induce supernumerary centrosomes under stress. (PMID:23653187)
• Studies indicate that autophosphorylation of Nek7 and Plk4 occurred through an intermolecular mechanism, the kinases Aurora-A and Chk2 followed an intramolecular mechanism. (PMID:23821772)
• PLK4 is a new NFkappaB target gene, providing a direct link between NFkappaB activity and centrosome duplication, with implications for the role of these transcription factors in tumorigenesis. (PMID:23974100)
• Plk4 dynamically localizes to distinct subcentrosomal regions by interacting with two hierarchically regulated scaffolds, Cep192 and Cep152. (PMID:24277814)
• it appears that Nek2 and Plk4 might synergize to promote breast tumorigenesis and may also be involved in tamoxifen and trastuzumab resistance (PMID:24389189)
• p53-Dependent and cell specific epigenetic regulation of the polo-like kinases under oxidative stress. (PMID:24498222)
• HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical (PMID:24588599)
• Results demonstrated that Plk4 is under the direct control of the E2F activators in breast cancer cells. (PMID:24797070)
• Studies indicate that overexpression of polo-like kinase 4 (PLK4) is found in several cancer and suggest the PLK4 inhibitors as anticancer therapeutics. (PMID:24867403)
• PLK4 overexpression induces centrosome amplification and chromosome instability and causes the suppression of primary cilia formation. (PMID:24981932)
• Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer. (PMID:24997597)
• Breast cancer cell viability is dependent on PLK4 expression. (PMID:25043604)
• An unexpected activity of Plk4 that promotes cell migration and may underlie an association between increased Plk4 expression, cancer progression and death from metastasis in solid tumor patients. (PMID:25174401)
• Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. (PMID:25320347)
• Negative feedback by centriolar STIL regulates bimodal centriolar distribution of Plk4 and seemingly restricts occurrence of procentriole formation to one site on each parental centriole. (PMID:25342035)
• different levels of impaired PLK4 activity result in growth and cilia phenotypes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features (PMID:25344692)
• Decreased PLK4 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies. (PMID:25347426)
• PLK4 functions downstream of ROCK2 to drive centrosome amplification in arrested cells. (PMID:25590559)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plk4	ENSDARG00000004576
mus_musculus	Plk4	ENSMUSG00000025758
rattus_norvegicus	Plk4	ENSRNOG00000011654
drosophila_melanogaster	SAK	FBGN0026371

Paralogs (4): PLK2 (ENSG00000145632), PLK1 (ENSG00000166851), PLK3 (ENSG00000173846), PLK5 (ENSG00000185988)

Protein

Protein identifiers

Serine/threonine-protein kinase PLK4 — O00444 (reviewed: O00444)

Alternative names: Polo-like kinase 4, Serine/threonine-protein kinase 18, Serine/threonine-protein kinase Sak

All UniProt accessions (4): O00444, H0YAL6, J3KR82, J3KR84

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates ‘Ser-151’ of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification. Phosphorylates CEP131 at ‘Ser-78’ and PCM1 at ‘Ser-372’ which is essential for proper organization and integrity of centriolar satellites.

Subunit / interactions. Homodimer. Interacts with CEP152 (via N-terminus). Interacts with CEP78; this interaction may be important for proper PLK4 localization to the centriole and PLK4-induced overduplication of centrioles. Interacts with CEP131. Interacts simultaneously with TENT5C and CEP192. Interacts with TENT5C; this interaction leads to the TENT5C recruitment in the centrosome. Interacts with CEP85; this interaction may be important in cell migration and centriole assembly.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Nucleus. Nucleolus. Cleavage furrow.

Post-translational modifications. Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation. Ubiquitinated; leading to its degradation by the proteasome. Deubiquitinated by USP54; leading to PLK4 stabilization. Tyrosine-phosphorylated by TEC.

Disease relevance. Microcephaly and chorioretinopathy, autosomal recessive, 2 (MCCRP2) [MIM:616171] A severe disorder characterized by microcephaly, delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Cryptic POLO box 1 (CPB1) and Cryptic POLO box 2 (CPB2) domains can simultaneously bind to both TENT5C and CEP192.

Induction. Down-regulated in HCT 116 colorectal cancer cells, leading to aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. Down-regulated by p53/TP53.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O00444-1	1	yes
O00444-2	2
O00444-3	3

RefSeq proteins (3): NP_001177728, NP_001177730, NP_055079* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000959	POLO_box_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR033696	POLO_box_Plk4_C	Domain
IPR033698	POLO_box_Plk4_2	Domain
IPR033699	POLO_box_Plk4_1	Domain
IPR046437	Ser_Thr-PK_POLO_box_1_sf	Homologous_superfamily
IPR047108	Plk4-like_POLO_box_2_sf	Homologous_superfamily

Pfam: PF00069, PF18190, PF18409

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 (100 total): strand 27, helix 20, mutagenesis site 9, sequence variant 8, sequence conflict 8, compositionally biased region 5, modified residue 5, turn 5, domain 4, region of interest 3, binding site 2, splice variant 2, chain 1, active site 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
9Y9N	X-RAY DIFFRACTION	1.81
3COK	X-RAY DIFFRACTION	2.25
9O63	X-RAY DIFFRACTION	2.26
4JXF	X-RAY DIFFRACTION	2.4
5LHZ	X-RAY DIFFRACTION	2.51
4YYP	X-RAY DIFFRACTION	2.6
4N9J	X-RAY DIFFRACTION	2.6
6N45	X-RAY DIFFRACTION	2.64
4YUR	X-RAY DIFFRACTION	2.65
8XPG	X-RAY DIFFRACTION	2.7
9Y9B	X-RAY DIFFRACTION	2.7
4N7V	X-RAY DIFFRACTION	2.76
4N7Z	X-RAY DIFFRACTION	2.85
5LHY	X-RAY DIFFRACTION	3.31
6N46	X-RAY DIFFRACTION	3.71
6W3I	X-RAY DIFFRACTION	3.8
6W3J	X-RAY DIFFRACTION	4.38
6W38	X-RAY DIFFRACTION	4.48
2N19	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00444-F1	66.31	0.37

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): 136 (proton acceptor)

Ligand- & substrate-binding residues (2): 18–26; 41

Post-translational modifications (5): 45, 46, 401, 665, 817

Mutagenesis-validated functional residues (9):

Position	Phenotype
13	does not affect interaction with ubp54.
41	abolishes ability to phosphorylate cdc25c and chek2.
151	does not affect interaction with ubp54.
154	catalytically inactive mutant that causes some centrosome amplification above background levels when overexpressed.
162	abolishes interaction with ubp54.
167	does not affect interaction with ubp54.
170	activating mutant.
669	does not affect the interaction with tent5c.
670	decreases substantially the interaction with tent5c. does not affect localization to the centrosome. loss of tent5c recr

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
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-8854518	AURKA Activation by TPX2

MSigDB gene sets: 492 (showing top): E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, SEMBA_FHIT_TARGETS_DN, CCAWYNNGAAR_UNKNOWN, CROONQUIST_NRAS_SIGNALING_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KENNY_CTNNB1_TARGETS_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GENTILE_RESPONSE_CLUSTER_D3

GO Biological Process (7): protein phosphorylation (GO:0006468), centriole replication (GO:0007099), positive regulation of centriole replication (GO:0046601), cilium assembly (GO:0060271), trophoblast giant cell differentiation (GO:0060707), de novo centriole assembly involved in multi-ciliated epithelial cell differentiation (GO:0098535), regulation of cell cycle process (GO:0010564)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), identical protein binding (GO:0042802), 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): XY body (GO:0001741), nucleus (GO:0005634), nucleolus (GO:0005730), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cleavage furrow (GO:0032154), deuterosome (GO:0098536), procentriole (GO:0120098), procentriole replication complex (GO:0120099), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
cytoplasm	3
cellular anatomical structure	3
cell cycle process	2
protein kinase activity	2
microtubule organizing center	2
phosphorylation	1
protein modification process	1
centrosome duplication	1
centriole assembly	1
centriole replication	1
regulation of centriole replication	1
positive regulation of cytoskeleton organization	1
positive regulation of cell cycle process	1
positive regulation of organelle assembly	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cell differentiation involved in embryonic placenta development	1
de novo centriole assembly	1
multi-ciliated epithelial cell differentiation	1
regulation of cell cycle	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
sex chromosome	1
condensed chromatin of inactivated sex chromosome	1

Protein interactions and networks

STRING

3358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLK4	CEP152	O94986	992
PLK4	SASS6	Q6UVJ0	989
PLK4	CEP135	Q66GS9	982
PLK4	CPAP	Q9HC77	982
PLK4	CCP110	O43303	962
PLK4	CEP192	Q8TEP8	956
PLK4	STIL	Q15468	942
PLK4	PLG	P00747	924
PLK4	TUBG1	P23258	900
PLK4	PCNT	O95613	882
PLK4	CNTLN	Q9NXG0	849
PLK4	BUB1B	O60566	843
PLK4	CEP63	Q96MT8	838
PLK4	CETN2	P41208	832
PLK4	NEDD1	Q8NHV4	802

IntAct

154 interactions, top by confidence:

A	B	Type	Score
PLK4	CEP152	psi-mi:“MI:0915”(physical association)	0.850
CEP152	PLK4	psi-mi:“MI:0915”(physical association)	0.850
PLK4	CEP152	psi-mi:“MI:0914”(association)	0.850
PLK4	PLK4	psi-mi:“MI:0915”(physical association)	0.830
PLK4	CEP152	psi-mi:“MI:0407”(direct interaction)	0.830
PLK4	CEP152	psi-mi:“MI:0915”(physical association)	0.830
PLK4	PLK4	psi-mi:“MI:0914”(association)	0.830
PLK4	PLK4	psi-mi:“MI:0407”(direct interaction)	0.830

BioGRID (182): PLK4 (Two-hybrid), PLK4 (Two-hybrid), PLK4 (Two-hybrid), C1orf109 (Two-hybrid), PLK4 (Two-hybrid), FAM46C (Two-hybrid), MTUS2 (Two-hybrid), PLK4 (Two-hybrid), MIB1 (Affinity Capture-Western), PLK4 (Affinity Capture-Western), PLK4 (Affinity Capture-Western), SDCCAG3 (Proximity Label-MS), CEP152 (Proximity Label-MS), CEP192 (Proximity Label-MS), CEP85 (Proximity Label-MS)

ESM2 similar proteins: A0A078CGE6, A2QHV0, A7KAX9, A7SNN5, A9RVK2, B0XPE7, B5X564, D0Z5N4, F4HYG2, F4I114, F4IRW0, F4J394, F4J6F6, F4JY37, O00444, O13839, O24527, O43065, P0CP71, P13185, P38623, P42858, P50526, Q03407, Q0CL79, Q0WPH8, Q14693, Q19192, Q2KHT3, Q2QAV0, Q4WJI7, Q5B4Z3, Q5R9Z7, Q60DG4, Q6GPD0, Q6H647, Q756Z0, Q75CH3, Q75DK7, Q75QN6

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

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
PLK4	up-regulates	PLK4	phosphorylation
PLK4	up-regulates	CENPJ	phosphorylation
PLK4	“up-regulates activity”	PCM1	phosphorylation
PLK4	“up-regulates quantity”	CDC25C	phosphorylation
PLK4	“up-regulates activity”	CEP131	phosphorylation
PLK4	“up-regulates activity”	TUBGCP6	phosphorylation
PLK4	“up-regulates activity”	NEDD1	phosphorylation
PLK4	“down-regulates activity”	FBXW5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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 BAD and translocation to mitochondria	7	177.6×	3e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	156.8×	4e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	156.8×	4e-13
Activation of BH3-only proteins	7	115.9×	4e-12
RHO GTPases activate PKNs	7	74.0×	1e-10
Intrinsic Pathway for Apoptosis	7	68.3×	2e-10
FOXO-mediated transcription	5	56.0×	2e-07
Centrosome maturation	5	42.3×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	41.6×	3e-05
intracellular protein localization	7	16.6×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	9
Uncertain significance	357
Likely benign	249
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1021501	NM_014264.5(PLK4):c.1679del (p.Cys560fs)	Pathogenic
1075626	NM_014264.5(PLK4):c.60del (p.Gly21fs)	Pathogenic
1452199	NM_014264.5(PLK4):c.1201del (p.Ser401fs)	Pathogenic
1455498	NM_014264.5(PLK4):c.319_331del (p.Pro107fs)	Pathogenic
1457246	NM_014264.5(PLK4):c.168_169del (p.Arg56fs)	Pathogenic
1458419	NM_014264.5(PLK4):c.62del (p.Gly21fs)	Pathogenic
162400	NM_014264.5(PLK4):c.2811-5C>G	Pathogenic
1952871	NM_014264.5(PLK4):c.799C>T (p.Arg267Ter)	Pathogenic
1976021	NM_014264.5(PLK4):c.1567_1568insTTGT (p.Lys523fs)	Pathogenic
2028466	NM_014264.5(PLK4):c.419_420del (p.Leu139_Ser140insTer)	Pathogenic
2095296	NM_014264.5(PLK4):c.644_645del (p.Thr215fs)	Pathogenic
2098334	NM_014264.5(PLK4):c.2701C>T (p.Gln901Ter)	Pathogenic
2106876	NM_014264.5(PLK4):c.1796T>G (p.Leu599Ter)	Pathogenic
2147689	NM_014264.5(PLK4):c.1350_1353del (p.Asn450fs)	Pathogenic
2788633	NM_014264.5(PLK4):c.1261_1264del (p.Ser421fs)	Pathogenic
2839569	NM_014264.5(PLK4):c.585_604dup (p.Tyr202fs)	Pathogenic
2857037	NM_014264.5(PLK4):c.1116C>G (p.Tyr372Ter)	Pathogenic
2858483	NM_014264.5(PLK4):c.553C>T (p.Arg185Ter)	Pathogenic
3609134	NM_014264.5(PLK4):c.1111C>T (p.Arg371Ter)	Pathogenic
3644620	NM_014264.5(PLK4):c.1115dup (p.Tyr372Ter)	Pathogenic
3653686	NM_014264.5(PLK4):c.1531C>T (p.Gln511Ter)	Pathogenic
4710728	NM_014264.5(PLK4):c.1956del (p.Asn652fs)	Pathogenic
960158	NM_014264.5(PLK4):c.37A>T (p.Lys13Ter)	Pathogenic
1011819	NM_014264.5(PLK4):c.1830+1G>A	Likely pathogenic
1031259	NM_014264.5(PLK4):c.2562+1G>C	Likely pathogenic
1495735	NM_014264.5(PLK4):c.1358+1G>C	Likely pathogenic
2017507	NM_014264.5(PLK4):c.2563-1G>A	Likely pathogenic
2017890	NM_014264.5(PLK4):c.2707_2710del (p.Thr903fs)	Likely pathogenic
3064399	NM_014264.5(PLK4):c.1177_1181del (p.Thr393fs)	Likely pathogenic
3692104	NM_014264.5(PLK4):c.2323-1G>A	Likely pathogenic

SpliceAI

2094 predictions. Top by Δscore:

Variant	Effect	Δscore
4:127881926:GGTA:G	donor_loss	1.0000
4:127881927:G:A	donor_loss	1.0000
4:127881928:T:G	donor_loss	1.0000
4:127883437:A:AG	acceptor_gain	1.0000
4:127883438:G:GG	acceptor_gain	1.0000
4:127883438:GCTTT:G	acceptor_gain	1.0000
4:127883552:AG:A	donor_loss	1.0000
4:127883553:GGTA:G	donor_loss	1.0000
4:127883554:GTAG:G	donor_loss	1.0000
4:127885695:A:AG	acceptor_gain	1.0000
4:127885696:A:G	acceptor_gain	1.0000
4:127886724:GCACT:G	donor_gain	1.0000
4:127886729:G:GG	donor_gain	1.0000
4:127887394:A:AG	acceptor_gain	1.0000
4:127887395:G:GG	acceptor_gain	1.0000
4:127887495:TG:T	donor_gain	1.0000
4:127887495:TGGT:T	donor_loss	1.0000
4:127887496:GG:G	donor_gain	1.0000
4:127887497:G:GG	donor_gain	1.0000
4:127887498:T:A	donor_loss	1.0000
4:127889864:A:AG	acceptor_gain	1.0000
4:127889865:G:GG	acceptor_gain	1.0000
4:127889865:GCTC:G	acceptor_gain	1.0000
4:127891088:TTAG:T	acceptor_loss	1.0000
4:127891089:TAGG:T	acceptor_loss	1.0000
4:127891090:A:AG	acceptor_gain	1.0000
4:127891090:AG:A	acceptor_gain	1.0000
4:127891090:AGGT:A	acceptor_gain	1.0000
4:127891090:AGGTG:A	acceptor_gain	1.0000
4:127891091:G:A	acceptor_gain	1.0000

AlphaMissense

6425 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:127881835:T:C	F12S	1.000
4:127881861:G:A	G21R	1.000
4:127881861:G:C	G21R	1.000
4:127881862:G:A	G21E	1.000
4:127881867:T:C	F23L	1.000
4:127881869:T:A	F23L	1.000
4:127881869:T:G	F23L	1.000
4:127881871:C:A	A24D	1.000
4:127881919:T:A	I40N	1.000
4:127881921:A:G	K41E	1.000
4:127881923:A:C	K41N	1.000
4:127881923:A:T	K41N	1.000
4:127883305:T:A	V57D	1.000
4:127883476:T:C	L87P	1.000
4:127885774:G:C	R135P	1.000
4:127885777:A:C	D136A	1.000
4:127885777:A:G	D136G	1.000
4:127885777:A:T	D136V	1.000
4:127885830:G:C	D154H	1.000
4:127885831:A:C	D154A	1.000
4:127885831:A:G	D154G	1.000
4:127885831:A:T	D154V	1.000
4:127885832:T:A	D154E	1.000
4:127885832:T:G	D154E	1.000
4:127885840:T:C	L157P	1.000
4:127885888:G:A	G173E	1.000
4:127885953:T:A	W195R	1.000
4:127885953:T:C	W195R	1.000
4:127886092:T:C	L241P	1.000
4:127881834:T:C	F12L	0.999

dbSNP variants (sampled 300 via entrez): RS1000149678 (4:127888032 T>C), RS1000228830 (4:127888351 A>C), RS1000258093 (4:127883118 A>C,G), RS1000580128 (4:127892754 G>GT), RS1000961356 (4:127898767 C>A), RS1000967421 (4:127893024 C>A), RS1001012688 (4:127889851 C>G), RS1001274320 (4:127887344 T>C), RS1001522056 (4:127896549 T>G), RS1001585829 (4:127894033 C>G,T), RS1002222232 (4:127881044 G>A), RS1002244600 (4:127896948 A>C,G), RS1002273432 (4:127885541 T>A), RS1002275706 (4:127897363 C>T), RS1002327150 (4:127885813 T>A,C)

Disease associations

OMIM: gene MIM:605031 | disease phenotypes: MIM:616171, MIM:610951

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly and chorioretinopathy 2	Definitive	Autosomal recessive
microcephaly and chorioretinopathy 1	Supportive	Autosomal recessive
Seckel syndrome	Supportive	Autosomal recessive

Mondo (7): inherited retinal dystrophy (MONDO:0019118), microcephaly and chorioretinopathy 2 (MONDO:0014516), neuronal ceroid lipofuscinosis 7 (MONDO:0012588), optic atrophy (MONDO:0003608), microcephaly (MONDO:0001149), microcephaly and chorioretinopathy 1 (MONDO:0009624), Seckel syndrome (MONDO:0019342)

Orphanet (4): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Seckel syndrome (Orphanet:808), OBSOLETE: Late infantile neuronal ceroid lipofuscinosis (Orphanet:168491), CLN7 disease (Orphanet:228366)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000307	Pointed chin
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000494	Downslanted palpebral fissures
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000543	Optic disc pallor
HP:0000568	Microphthalmia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000682	Abnormal dental enamel morphology
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
C563989	Ceroid Lipofuscinosis, Neuronal, 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3788 (SINGLE PROTEIN), CHEMBL5465203 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

65 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 542,589 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2103830	FOSTAMATINIB	4	3,841
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL941	IMATINIB	4	111,611
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3426621	RIPASUDIL	3
CHEMBL428690	ALVOCIDIB	3
CHEMBL483158	ALISERTIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230609	FORETINIB	2
CHEMBL1231124	AZD-1480	2
CHEMBL124660	TANDUTINIB	2

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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
centrinone B	Inhibition	9.23	pKi
CZS-241	Inhibition	8.59	pIC50
ocifisertib	Inhibition	8.55	pIC50
RP-1664	Inhibition	8.52	pIC50
RG-1530	Inhibition	7.96	pKd
axitinib	Inhibition	7.34	pIC50
XMD8-92	Inhibition	6.22	pKd

Binding affinities (BindingDB)

47 measured of 283 human assays (285 total across all organisms); most potent 47 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
BMCL191018 Compound 2	IC50	2 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
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
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
(2’S,3R)-5-bromo-2’-(1H-indazol-6-yl)spiro[1H-pyrrolo[2,3-b]pyridine-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(3R)-5-methoxy-2’-[3-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(3R)-2’-[3-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(2’S,3R)-5-fluoro-2’-(3-iodo-2H-indazol-6-yl)spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(2’R,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(3R)-5-amino-2’-[3-[4-(4-methylpiperazin-1-yl)phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(1R,2S)-1’-methyl-2-[3-(4-piperazin-1-ylphenyl)-1H-indazol-6-yl]spiro[cyclopropane-1,3’-indole]-2’-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(2’S,3R)-2’-[3-[6-(4-hydroxypiperidin-1-yl)-3-pyridinyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(2’S,3R)-2’-[3-[4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[3-(morpholin-4-ylmethyl)phenyl]ethenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(2’S,3R)-2’-[3-[(E)-2-[3-[(dimethylamino)methyl]phenyl]ethenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(3R)-5,6-dimethoxy-2’-[3-[4-(4-methylpiperazin-1-yl)phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(3R)-5-methoxy-2’-[3-[2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethynyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(3R)-2’-[3-[3-(morpholin-4-ylmethyl)phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(3R)-2’-[3-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(3R)-2’-[3-[4-(4-methylpiperazin-1-yl)phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-(trifluoromethyl)spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(1R)-2-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]-1’-(3-methylbutyl)spiro[cyclopropane-1,3’-indole]-2’-one	IC50	550 nM	US-9907800: Kinase inhibitors and method of treating cancer
(2’S,3R)-2’-[3-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(2’S,3R)-2’-[3-[3-(morpholin-4-ylmethyl)phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	550 nM	US-10358436: Kinase inhibitors and method of treating cancer
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 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
(2’R,3S)-2’-(2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl)spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	2000 nM	US-10358436: Kinase inhibitors and method of treating cancer
(2’R,3S)-2’-(3-iodo-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl)-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	2000 nM	US-10358436: Kinase inhibitors and method of treating cancer
(3R)-2’-(2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl)spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	2000 nM	US-10358436: Kinase inhibitors and method of treating cancer
(3R)-5,6-dimethoxy-2’-[3-[3-(morpholin-4-ylmethyl)phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	2000 nM	US-10358436: Kinase inhibitors and method of treating cancer
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
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

911 potent at pChembl≥5 of 926 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	CHEMBL3408945
10.00	IC50	0.1	nM	CHEMBL5209160
9.80	Ki	0.16	nM	CHEMBL5185225
9.70	IC50	0.2	nM	CHEMBL5185001
9.59	Ki	0.26	nM	OCIFISERTIB
9.52	IC50	0.3	nM	CHEMBL5171469
9.52	IC50	0.3	nM	CHEMBL5428085
9.52	IC50	0.3	nM	CHEMBL5404983
9.49	IC50	0.32	nM	CHEMBL2407898
9.43	IC50	0.37	nM	CHEMBL3353348
9.41	IC50	0.39	nM	CHEMBL3408955
9.40	IC50	0.4	nM	CHEMBL5439790
9.35	IC50	0.45	nM	CHEMBL2407894
9.35	IC50	0.45	nM	CHEMBL4553351
9.32	IC50	0.48	nM	CHEMBL2407748
9.23	IC50	0.59	nM	CHEMBL3353347
9.22	IC50	0.6	nM	CHEMBL3408944
9.22	Ki	0.6	nM	CHEMBL5556344
9.21	IC50	0.61	nM	CHEMBL2407900
9.19	IC50	0.64	nM	CHEMBL3408954
9.16	IC50	0.69	nM	CHEMBL4516793
9.15	IC50	0.71	nM	CHEMBL3353351
9.15	IC50	0.7	nM	CHEMBL5171233
9.15	IC50	0.7	nM	CHEMBL5188129
9.15	IC50	0.7	nM	CHEMBL5183346
9.14	Ki	0.73	nM	CHEMBL3408946
9.12	IC50	0.75	nM	CHEMBL3353341
9.12	Kd	0.75	nM	STAUROSPORINE
9.11	Kd	0.77	nM	STAUROSPORINE
9.10	IC50	0.79	nM	CHEMBL3353352
9.10	IC50	0.8	nM	CHEMBL5200865
9.09	IC50	0.82	nM	CHEMBL2407744
9.05	IC50	0.9	nM	CHEMBL2407895
9.05	IC50	0.9	nM	CHEMBL3408941
9.05	IC50	0.9	nM	CHEMBL3353361
9.05	IC50	0.9	nM	CHEMBL3353362
9.05	IC50	0.9	nM	CHEMBL3353355
9.05	IC50	0.9	nM	CHEMBL5402864
9.03	IC50	0.94	nM	CHEMBL4448596
9.03	Kd	0.93	nM	TAE-684
9.00	IC50	1	nM	CHEMBL4516793
9.00	IC50	1	nM	CHEMBL5185324
9.00	IC50	1	nM	CHEMBL5420150
8.96	IC50	1.1	nM	CHEMBL3353348
8.96	IC50	1.1	nM	CHEMBL3353347
8.96	IC50	1.1	nM	CHEMBL3408956
8.96	IC50	1.1	nM	CHEMBL5194020
8.92	IC50	1.2	nM	CHEMBL3353350
8.92	IC50	1.2	nM	CHEMBL4440053
8.92	IC50	1.2	nM	CHEMBL4470693

PubChem BioAssay actives

534 with measured affinity, of 2091 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
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0001	uM
(1R,2S)-5’-methoxy-1’-methyl-2-[3-[(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[cyclopropane-1,3’-indole]-2’-one	1198709: Competitive binding to PLK4 (unknown origin) by double reciprocal plot analysis in presence of ATP	ki	0.0001	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0002	uM
2-[2-fluoro-4-[(2-fluoro-3-nitrophenyl)methylsulfonyl]phenyl]sulfanyl-5-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-ylpyrimidin-4-amine	2073833: Binding affinity to PLK4 (unknown origin) assessed as inhibition constant	ki	0.0002	uM
3-[(E)-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]indazol-6-ylidene]methyl]-5-methoxy-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0003	uM
6-N-[(4-chlorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0003	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[4-[(5-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[5,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0003	uM
5-[[[1-(1-acetylpiperidin-4-yl)-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]-2-chloro-N-(2,5-difluorophenyl)benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0003	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[[(2S,6R)-2,6-dimethylmorpholin-4-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1198709: Competitive binding to PLK4 (unknown origin) by double reciprocal plot analysis in presence of ATP	ki	0.0003	uM
5-methoxy-3-[(E)-[3-[(E)-2-pyridin-4-ylethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0004	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[1-(1,1-dioxothian-4-yl)-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0004	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[4-[[(2S,6R)-2,4,6-trimethylpiperazin-1-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0004	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0004	uM
(2’S,3R)-5-methoxy-2’-[3-(4-piperazin-1-ylphenyl)-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0004	uM
5-methoxy-3-[(E)-[3-[(E)-2-pyridin-3-ylethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0005	uM
2-[2-fluoro-4-[(2-fluoro-3-nitrophenyl)methylsulfonyl]phenyl]sulfanyl-5-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-6-piperidin-1-ylpyrimidin-4-amine	2073833: Binding affinity to PLK4 (unknown origin) assessed as inhibition constant	ki	0.0006	uM
5-methoxy-3-[(E)-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0006	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0006	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0006	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[4-(piperidin-1-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0006	uM
6-N-[(2-chlorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0007	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-ethyl-1H-pyrazol-3-yl)-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0007	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1-piperidin-4-ylpyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0007	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[[(2S,6R)-2,6-dimethylmorpholin-4-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198709: Competitive binding to PLK4 (unknown origin) by double reciprocal plot analysis in presence of ATP	ki	0.0007	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methylspiro[1H-indole-3,1’-cyclopropane]-2-one	1178617: Inhibition of human N-terminal GST-tagged PLK4 (1 to 391 residues) expressed in Escherichia coli incubated for 30 mins by ELISA method	ic50	0.0007	uM
(2’S,3R)-5-methoxy-2’-[3-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0007	uM
4-[(E)-2-[(6E)-6-[(2-hydroxy-1H-indol-3-yl)methylidene]indazol-3-yl]ethenyl]benzoic acid	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0008	uM
6-N-[(4-fluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0008	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	256607: Average Binding Constant for STK18; NA=Not Active at 10 uM	kd	0.0008	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0008	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-fluorospiro[1H-indole-3,1’-cyclopropane]-2-one	1178617: Inhibition of human N-terminal GST-tagged PLK4 (1 to 391 residues) expressed in Escherichia coli incubated for 30 mins by ELISA method	ic50	0.0008	uM
3-[(E)-[3-[(E)-2-pyridin-4-ylethenyl]indazol-6-ylidene]methyl]-1H-indole-2,5-diol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0009	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625076: Binding constant for PLK4 kinase domain	kd	0.0009	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[4-[(5-methyl-1H-pyrazol-3-yl)amino]-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0009	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
(2’S,3R)-2’-[3-[(E)-2-(4-piperazin-1-ylphenyl)ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
(2’S,3R)-2’-[3-[(E)-2-[4-(piperidin-1-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
(2’S,3R)-5-methoxy-2’-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0009	uM
(2’S,3R)-2’-[3-[(E)-2-[4-(pyrrolidin-1-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
6-N-[(2-fluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0010	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[4-[(5-methyl-1H-pyrazol-3-yl)amino]-1-(1-methylsulfonylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0010	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0011	uM
(2’S,3R)-2’-[3-[(E)-2-[4-(1-methylpiperidin-4-yl)oxyphenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0011	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[1-methyl-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0012	uM
(2’S,3R)-2’-[3-[4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]phenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0012	uM
(2’S,3R)-2’-[3-[4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0012	uM
(2’S,3R)-5-chloro-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1178617: Inhibition of human N-terminal GST-tagged PLK4 (1 to 391 residues) expressed in Escherichia coli incubated for 30 mins by ELISA method	ic50	0.0012	uM
(1R,2S)-1’-methyl-2-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]-1H-indazol-6-yl]spiro[cyclopropane-1,3’-indole]-2’-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0013	uM
5-methyl-3-[(E)-[3-[(E)-2-pyridin-4-ylethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0014	uM
3-[(E)-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0014	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, affects expression, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
Cyclosporine	decreases expression	3
bisphenol A	increases expression, decreases expression	2
Resveratrol	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Estradiol	increases expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	affects binding, increases reaction, increases localization, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
afuresertib	decreases expression	1
echimidine	increases metabolic processing, decreases expression	1
dicrotophos	decreases expression	1
diminazene aceturate	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
trichostatin A	affects expression	1
riddelliine	increases metabolic processing, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
caffeic acid	increases reaction, increases expression	1
beta-methylcholine	affects expression	1
phenethyl isothiocyanate	decreases expression	1
tamibarotene	decreases expression	1
4-methoxycinnamate methyl ester	increases expression, increases reaction	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

303 unique, capped per target: 293 binding, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004495	Binding	Binding affinity to human recombinant PLK4 expressed in Escherichia coli assessed as thermal shift by differential scanning fluorimetry	Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone. — Bioorg Med Chem
CHEMBL1963705	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PLK4	PubChem BioAssay data set

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04737460	PHASE1	ACTIVE_NOT_RECRUITING	Study for the Treatment for CLN7 Disease
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT03139903	Not specified	COMPLETED	The Primordial Dwarfisms: Diagnosis, Identification of the Molecular Basis of Seckel Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment