CDK6

Summary

CDK6 (cyclin dependent kinase 6, HGNC:1777) is a protein-coding gene on chromosome 7q21.2, encoding Cyclin-dependent kinase 6 (Q00534). Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. In precision oncology, CDK6 Overexpression confers sensitivity to Palbociclib in Breast Cancer (CIViC Level B); 4 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 52.1% of cell lines).

The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly.

Source: NCBI Gene 1021 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive primary microcephaly (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 132
• Clinical variants (ClinVar): 53 total — 1 pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes — 45 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 5 curated variant–drug associations
• Cancer dependency (DepMap): dependent in 52.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001145306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1777
Approved symbol	CDK6
Name	cyclin dependent kinase 6
Location	7q21.2
Locus type	gene with protein product
Status	Approved
Aliases	PLSTIRE
Ensembl gene	ENSG00000105810
Ensembl biotype	protein_coding
OMIM	603368
Entrez	1021

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000265734, ENST00000424848, ENST00000467166, ENST00000473078, ENST00000491250, ENST00000906279, ENST00000906280, ENST00000906281, ENST00000906282, ENST00000906283, ENST00000930022, ENST00000961497

RefSeq mRNA: 2 — MANE Select: NM_001145306 NM_001145306, NM_001259

CCDS: CCDS5628

Canonical transcript exons

ENST00000424848 — 8 exons

Exon	Start	End
ENSE00000705199	92618072	92618207
ENSE00000705202	92623036	92623086
ENSE00000877375	92774696	92774831
ENSE00000877376	92725626	92725793
ENSE00001132651	92833091	92833690
ENSE00001723825	92836478	92836573
ENSE00001764561	92671426	92671535
ENSE00001927584	92604921	92615286

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 97.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.7390 / max 2672.1913, expressed in 1806 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84845	22.0963	1581
84840	8.4209	1587
84839	1.3954	651
84834	1.1251	656
84846	0.9221	536
84848	0.7762	266
84844	0.7014	342
84837	0.5731	186
84849	0.5135	154
84838	0.4199	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.02	gold quality
trabecular bone tissue	UBERON:0002483	94.70	gold quality
pylorus	UBERON:0001166	94.25	gold quality
caput epididymis	UBERON:0004358	93.50	gold quality
cardia of stomach	UBERON:0001162	92.26	gold quality
cartilage tissue	UBERON:0002418	92.05	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.10	gold quality
nipple	UBERON:0002030	90.80	gold quality
parietal pleura	UBERON:0002400	90.43	gold quality
oral cavity	UBERON:0000167	90.36	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.21	gold quality
inferior vagus X ganglion	UBERON:0005363	88.96	gold quality
bone marrow	UBERON:0002371	88.90	gold quality
renal medulla	UBERON:0000362	88.48	gold quality
colonic epithelium	UBERON:0000397	88.20	gold quality
pleura	UBERON:0000977	88.18	gold quality
skin of hip	UBERON:0001554	88.15	gold quality
cauda epididymis	UBERON:0004360	88.01	gold quality
colonic mucosa	UBERON:0000317	87.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.70	gold quality
upper leg skin	UBERON:0004262	87.47	gold quality
visceral pleura	UBERON:0002401	87.43	gold quality
mammalian vulva	UBERON:0000997	87.36	gold quality
jejunal mucosa	UBERON:0000399	86.84	gold quality
superior surface of tongue	UBERON:0007371	86.65	gold quality
mammary duct	UBERON:0001765	86.56	gold quality
tibia	UBERON:0000979	86.17	gold quality
pigmented layer of retina	UBERON:0001782	85.91	gold quality
retina	UBERON:0000966	85.89	gold quality
ventricular zone	UBERON:0003053	85.70	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-GEOD-150728	yes	1315.94
E-CURD-79	yes	573.44
E-CURD-55	yes	452.80
E-GEOD-149689	yes	411.12
E-CURD-77	yes	386.31
E-HCAD-6	yes	352.29
E-MTAB-8495	yes	303.99
E-HCAD-4	yes	80.22
E-CURD-112	yes	39.67
E-CURD-119	yes	33.53
E-GEOD-125970	yes	17.54
E-HCAD-1	yes	15.13
E-MTAB-6701	yes	10.85
E-MTAB-8271	yes	7.94
E-GEOD-93593	yes	7.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, GATA1, GLI3, ID1, KDM2A, MAFK, MITF, MYB, MYC, NANOG, NFKB2, NFKB, NR3C1, PAX6, RBPJ, RELA, RUNX1, SMAD6, SP1, SPI1, STAT5B, TCF3, TP53, TRIP6, ZNF382

miRNA regulators (miRDB)

601 targeting CDK6, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5193	100.00	67.26	1744
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 52.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• KSHV-cyclin can activate CDK6 independent of phosphorylation by CAK in vitro (PMID:11739795)
• crystal structure of human CDK6–Vcyclin in an active state was determined to 3.1 A resolution to better understand the structural basis of CDK6 activation by viral cyclins (PMID:11828325)
• a patient with the dignosis of B-cell lymphoma with cdk6 expression is dysregulated mapping to chromosome 7. (PMID:11940479)
• Sequential extension of proliferative lifespan in human fibroblasts is induced by over-expression of CDK4 or 6 and loss of p53 function. (PMID:12082615)
• Overexpression of transfected human Cdk6 & mouse cyclin D3 enhances susceptibility of BALB/c3T3 & C3H10T1/2 mouse fibroblast lines to UV radiation & 3-methylcholanthrene transformation. (PMID:12592386)
• cyclin-dependent kinase (CDK)2, -4, and -6 were down-regulated from the myelocytes/metamyelocytes stages and onward (PMID:14694185)
• cdk6 restrains rather than stimulates breast epithelial cell proliferation and that its loss or down-regulation could play a role in breast tumor development (PMID:14985467)
• the amount of CDK6 was reduced by TNF-alpha, while CDK6 and the FLICE-inhibitory protein (FLIP) were increased with SCF (PMID:15504546)
• c-Myb activity is directly regulated by cyclin D1 and CDKs and imply that c-Myb activity is regulated during the cell cycle in hematopoietic cells (PMID:15687240)
• CDK6 may play an important role in the development and/or progression of a subset of human prostate cancers by stimulating the activity of the AR. (PMID:15790678)
• Overexpression of CDK6 correlated significantly with poor prognosis and represented an independent prognostic marker of overall survival in medulloblastoma. (PMID:16314645)
• CDK6 delays senescence by kinase-dependent and p16INK4a-independent mechanisms. (PMID:17420273)
• Amplification of the CDK6 locus was analyzed in primary T-cell lymphoma samples and, while detected infrequently in those classified as ALCL (1%), was detected in 23% of peripheral T-cell lymphomas not otherwise specified. (PMID:17989712)
• cdk phosphorylation of RUNX1 potentially couples stem/progenitor proliferation and lineage progression (PMID:18003885)
• Cdk6 up-regulation in TDP-43-depleted cells is accompanied by an increase in phosphorylation of two of its major targets, the retinoblastoma protein pRb and pRb-related protein pRb2/p130. (PMID:18305152)
• An atypical nevus susceptibility gene has been mapped to chromosome band 7q21.3 containing CDK6. (PMID:18398432)
• miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). (PMID:18406353)
• high-resolution genomic analysis and immunoprofiling identify CDK6 as the main candidate target for the recurrent amplification of 7q21 in GEJ adenocarcinomas (PMID:18438866)
• Amplification of CDK6 is associated with type I endometrial carcinoma tumors (PMID:18497076)
• Tax-induced cell-cycle progression in T cells is mediated, at least in part, through cell-type-specific activation of the cyclin D2 and cdk6 genes through NF-kappaB and may be important for the cell-type-specific oncogenesis. (PMID:18504428)
• CDK6 is regulated by microRNA 124 in medulloblastoma and that miR 124 modulates medulloblastoma cell growth. (PMID:18607543)
• Proliferation parameters of differentiating cells correlate with the activity and structure of cyclin A/E-CDK2 but not of cyclin D-CDK4/6-p27 complexes. (PMID:19040567)
• Cdk-6 overexpression, alone or in combination with cyclin D1, strikingly stimulates human beta-cell replication, both in vitro as well as in vivo, without inducing cell death or loss of function. (PMID:19136653)
• Report clinicopathologic features of CDK6 translocation-associated B-cell lymphoproliferative disorders. (PMID:19145199)
• MicroRNA repression is associated with repression of CDK6 in pancreatic cancer. (PMID:19407485)
• Grounds for new therapeutic strategies in acute lymphoblastic leukemia either by targeting the epigenetic regulation of microRNAs and/or directly targeting the CDK6 pathway. (PMID:19435910)
• Results show that substituting a proline for the corresponding residue of CDK6 enforced its complete, apparently cyclin-independent T177 phosphorylation and dramatically increased its activity. (PMID:19487459)
• miR-449a/b targets and inhibits oncogenic CDK6 and CDC25A, resulting in pRb dephosphorylation and cell cycle arrest at G1 phase, revealing a negative feedback regulation of the pRb-E2F1 pathway (PMID:19833767)
• Data show that SHP-1 knockdown increases p27stability, decreases the CDK6 levels, inducing retinoblastoma protein hypophosphorylation, downregulation of cyclin E and thereby a decrease in the CDK2 activity. (PMID:19838216)
• The majority of tumours showed strong p16, p21, p27, pRb and cyclin D1 staining and little or no p53 expression. Tumours harbouring dysplasia were significantly more likely to be p53-positive and exhibit up-regulated p21 and p27. (PMID:19863319)
• miR-29 inhibits CDK6 protein & mRNA levels by direct binding to 3’-untranslated region. Inverse correlation between miR-29 & CDK6 was observed in mantle-cell lymphoma. (PMID:20086245)
• CDK4/6 inhibition is a potent mediator of cytostasis and that RB loss can be readily compensated for in the context of both hepatoma cell lines and liver tissue. (PMID:20100483)
• These data suggest that the functional availability of Kaposi’s sarcoma-associated herpesvirus K-cyclin is largely dependent on the balance in expression between cellular CDK6 and p16INK4a. (PMID:20331971)
• KSHV v-cyclin and cellular CDK6 kinase phosphorylate NPM on threonine 199 (Thr199) in de novo and naturally Kaposi sarcoma herpesvirus-infected cells (PMID:20333249)
• cyclin-dependent kinase 4 and 6 inhibition arrests the growth of glioblastoma multiforme intracranial xenografts (PMID:20354191)
• lower expression in dysplastic nevi than in melanomas, but higher than in common nevi (PMID:20496072)
• analysis of a subset of glioblastoma multiforme likely to respond to CDK4/6 inhibition (PMID:20534551)
• For cdk6 staining, the prevalence of positive cases and the percentage of positive cells in normal mucosa were significantly lower than oral squamous cell carcinoma. (PMID:20618617)
• The level of cyclin-dependent kinase 6 (CDK6) is dramatically and selectively elevated in parkin-expressing breast cancer cells, the extent of which correlates well with the expression of parkin. (PMID:20630868)
• Targeted inhibition of CDK4 activity may have a role in the treatment of cyclin D-overexpressing breast cancers. (PMID:20736297)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk6	ENSDARG00000070228
mus_musculus	Cdk6	ENSMUSG00000040274
rattus_norvegicus	Cdk6	ENSRNOG00000009258

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 6 — Q00534 (reviewed: Q00534)

Alternative names: Cell division protein kinase 6, Serine/threonine-protein kinase PLSTIRE

All UniProt accessions (1): Q00534

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases.

Subunit / interactions. Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177. Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding. Interacts with Kaposi’s sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V-cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and thus lead to viral reactivation by reducing viral LANA levels.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Ruffle. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells.

Post-translational modifications. Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.

Disease relevance. Microcephaly 12, primary, autosomal recessive (MCPH12) [MIM:616080] A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation. Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast).

Induction. Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry.

Polymorphism. Genetic variations in CDK6 may influence stature as a quantitative trait, contributing to the stature quantitative trait locus 11 (STQTL11) [MIM:612223]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits.

Miscellaneous. Over-expressed in some leukemias and malignancies (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a consequence of nearby translocations. Enhances beta-cells engraftment in pancreatic islets of Langerhans of diabetic patients.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

RefSeq proteins (2): NP_001138778, NP_001250 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR028788	CDK6	Family
IPR050108	CDK	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.22 — cyclin-dependent kinase (BRENDA: 49 organisms, 441 substrates, 555 inhibitors, 8 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADAQHATPPKKKRKVEDPKDF	0.046–0.521	2
ATP	0.0052–0.017	2
FIN1	0.003	1
PKTPKKAKKL	0.0029	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 (46 total): helix 16, strand 11, modified residue 8, sequence variant 3, turn 3, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
9PE8	X-RAY DIFFRACTION	1.8
1BLX	X-RAY DIFFRACTION	1.9
6OQO	X-RAY DIFFRACTION	1.98
9D8U	X-RAY DIFFRACTION	2
9PE7	X-RAY DIFFRACTION	2.05
5L2S	X-RAY DIFFRACTION	2.27
4AUA	X-RAY DIFFRACTION	2.31
5L2T	X-RAY DIFFRACTION	2.37
3NUP	X-RAY DIFFRACTION	2.6
3NUX	X-RAY DIFFRACTION	2.7
4EZ5	X-RAY DIFFRACTION	2.7
6OQL	X-RAY DIFFRACTION	2.71
5L2I	X-RAY DIFFRACTION	2.75
8I0M	X-RAY DIFFRACTION	2.78
1BI8	X-RAY DIFFRACTION	2.8
2F2C	X-RAY DIFFRACTION	2.8
1G3N	X-RAY DIFFRACTION	2.9
1XO2	X-RAY DIFFRACTION	2.9
4TTH	X-RAY DIFFRACTION	2.9
2EUF	X-RAY DIFFRACTION	3
1JOW	X-RAY DIFFRACTION	3.1
1BI7	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00534-F1	85.81	0.63

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): 145 (proton acceptor)

Ligand- & substrate-binding residues (2): 19–27; 43

Post-translational modifications (8): 177, 264, 325, 1, 13, 24, 49, 70

Function

Pathways and Gene Ontology

Reactome pathways

28 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-69231	Cyclin D associated events in G1
R-HSA-8934593	Regulation of RUNX1 Expression and Activity
R-HSA-9630794	Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
R-HSA-9632700	Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
R-HSA-9754119	Drug-mediated inhibition of CDK4/CDK6 activity
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-69236	G1 Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9630747	Diseases of Cellular Senescence
R-HSA-9630750	Evasion of Oncogene Induced Senescence Due to p16INK4A Defects
R-HSA-9632693	Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects
R-HSA-9659787	Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects
R-HSA-9675126	Diseases of mitotic cell cycle
R-HSA-9675132	Diseases of cellular response to stress
R-HSA-9687139	Aberrant regulation of mitotic cell cycle due to RB1 defects

MSigDB gene sets: 700 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, AHRARNT_01, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_DENTATE_GYRUS_DEVELOPMENT, CREL_01, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_MYELOID_CELL_HOMEOSTASIS, MODULE_169, GOBP_EPITHELIAL_CELL_DEVELOPMENT, SP3_Q3

GO Biological Process (38): G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of cell-matrix adhesion (GO:0001954), type B pancreatic cell development (GO:0003323), DNA damage response (GO:0006974), signal transduction (GO:0007165), Notch signaling pathway (GO:0007219), negative regulation of cell population proliferation (GO:0008285), response to virus (GO:0009615), regulation of G2/M transition of mitotic cell cycle (GO:0010389), regulation of gene expression (GO:0010468), positive regulation of gene expression (GO:0010628), astrocyte development (GO:0014002), dentate gyrus development (GO:0021542), lateral ventricle development (GO:0021670), T cell differentiation in thymus (GO:0033077), gliogenesis (GO:0042063), cell dedifferentiation (GO:0043697), negative regulation of cell differentiation (GO:0045596), negative regulation of myeloid cell differentiation (GO:0045638), regulation of erythrocyte differentiation (GO:0045646), negative regulation of monocyte differentiation (GO:0045656), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of cell cycle (GO:0045786), positive regulation of fibroblast proliferation (GO:0048146), generation of neurons (GO:0048699), negative regulation of epithelial cell proliferation (GO:0050680), cell division (GO:0051301), regulation of cell cycle (GO:0051726), hematopoietic stem cell differentiation (GO:0060218), regulation of hematopoietic stem cell differentiation (GO:1902036), regulation of cell motility (GO:2000145), negative regulation of cellular senescence (GO:2000773), hematopoietic progenitor cell differentiation (GO:0002244), protein phosphorylation (GO:0006468), hemopoiesis (GO:0030097), cell differentiation (GO:0030154), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (11): cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), cyclin binding (GO:0030332), FBXO family protein binding (GO:0098770), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), ruffle (GO:0001726), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cyclin D1-CDK6 complex (GO:0097131), cyclin D2-CDK6 complex (GO:0097132), cyclin D3-CDK6 complex (GO:0097133), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Cellular Senescence	3
G1 Phase	1
Transcriptional regulation by RUNX1	1
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1
Cyclin D associated events in G1	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Cell Cycle, Mitotic	1
Mitotic G1 phase and G1/S transition	1
Cell Cycle	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cyclin-dependent protein kinase holoenzyme complex	3
negative regulation of cellular process	2
gene expression	2
anatomical structure development	2
protein binding	2
protein kinase activity	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
epithelial cell development	1
type B pancreatic cell differentiation	1
cellular response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
response to other organism	1
G2/M transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
regulation of macromolecule biosynthetic process	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
glial cell development	1
astrocyte differentiation	1
hippocampus development	1
telencephalon development	1
ventricular system development	1
T cell differentiation	1

Protein interactions and networks

STRING

6068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK6	CDKN2A	P42771	999
CDK6	CCNL2	Q96S94	999
CDK6	CCND1	P24385	998
CDK6	CDKN2B	P42772	998
CDK6	CCND2	P30279	997
CDK6	CDKN2C	P42773	997
CDK6	CCND3	P30281	997
CDK6	CDKN2D	P55273	997
CDK6	CDKN1A	P38936	995
CDK6	CCNA2	P20248	994
CDK6	CCNA1	P78396	987
CDK6	CDKN1B	P46527	984
CDK6	CDK4	P11802	983
CDK6	CDK2	P24941	963
CDK6	CCNE1	P24864	885

IntAct

281 interactions, top by confidence:

A	B	Type	Score
CCND1	CDK4	psi-mi:“MI:0914”(association)	0.990
CCND3	CDK4	psi-mi:“MI:0914”(association)	0.980
CDK6	CDKN2C	psi-mi:“MI:0915”(physical association)	0.970
CDK6	CCND3	psi-mi:“MI:0915”(physical association)	0.970
CDKN2C	CDK6	psi-mi:“MI:0915”(physical association)	0.970
CCND3	CDK6	psi-mi:“MI:2364”(proximity)	0.970
CCND3	CDK6	psi-mi:“MI:0915”(physical association)	0.970
CDKN2C	CDK4	psi-mi:“MI:0914”(association)	0.970

BioGRID (418): CDK6 (Two-hybrid), CDKN2B (Two-hybrid), CDKN2C (Two-hybrid), CDKN2D (Two-hybrid), DAB1 (Two-hybrid), PSMA3 (Two-hybrid), RB1 (Biochemical Activity), HIST1H1A (Biochemical Activity), CDK6 (Affinity Capture-MS), CDKN2B (Affinity Capture-MS), CDKN2A (Affinity Capture-MS), CDKN2D (Affinity Capture-MS), RTFDC1 (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), CDKN2C (Affinity Capture-MS)

ESM2 similar proteins: A8WIP6, A8XA58, G5EFV5, O13958, O61847, P06242, P17157, P20911, P23573, P25859, P34556, P50613, P50750, P51952, P51953, P54664, P54665, Q00534, Q00646, Q03147, Q06309, Q0J4I1, Q12126, Q2V419, Q38775, Q3TZA2, Q4KM34, Q4V862, Q5EAB2, Q5R7I7, Q5ZKN1, Q641Z4, Q64261, Q6FKD4, Q6GLD8, Q6ZAG3, Q7ZX42, Q8IZL9, Q8L4P8, Q8LF80

Diamond homologs: A2AAJ9, A3LN91, A4PES0, A4QNA8, A5D791, A7A1P0, B5VNQ3, D0Z5N4, D2HHP1, E1BTE1, E2RSS3, F4HPN2, G5ECH7, O13889, O18209, O57473, O77819, O88850, P07527, P08458, P09759, P0C1S8, P15442, P19525, P20793, P20794, P22216, P23561, P27466, P30291, P33279, P47810, P47817, P54350, P54665, P54666, P54762, P70335, P74297, P83100

SIGNOR signaling

34 interactions.

A	Effect	B	Mechanism
MYC	“up-regulates quantity by expression”	CDK6	“transcriptional regulation”
CDK6	unknown	RBL2	phosphorylation
CDK6	down-regulates	RB1	phosphorylation
CDK6	up-regulates	RUNX1	phosphorylation
CDK6	“up-regulates activity”	RUNX1	phosphorylation
CDK6	up-regulates	CDKN1B	phosphorylation
CDK6	down-regulates	CDKN1B	phosphorylation
CDKN2A	down-regulates	CDK6	binding
CDK6	“down-regulates activity”	CDKN1A	phosphorylation
4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide	down-regulates	CDK6	“chemical inhibition”
alvocidib	down-regulates	CDK6	“chemical inhibition”
“alvocidib hydrochloride”	down-regulates	CDK6	“chemical inhibition”
palbociclib	down-regulates	CDK6	“chemical inhibition”
CDK6	“form complex”	CyclinD1/CDK6	binding
SAAL1	“up-regulates quantity by expression”	CDK6	“post transcriptional regulation”
“NUP98 Fusion”	“up-regulates quantity by expression”	CDK6	“transcriptional regulation”
CDC25A	“up-regulates activity”	CDK6	dephosphorylation
CDK6	“up-regulates activity”	FOXO3	phosphorylation
CDK6	“down-regulates activity”	PKM	phosphorylation
CDK6	“up-regulates activity”	TFEB	phosphorylation
CDK6	“up-regulates activity”	TFE3	phosphorylation
CDK6	“up-regulates quantity”	JUN	phosphorylation
CDKN1A	down-regulates	CDK6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	8	65.1×	1e-11
G1 Phase	12	60.6×	4e-17
Cyclin D associated events in G1	15	44.8×	3e-19
Mitotic G1 phase and G1/S transition	17	40.1×	8e-21
G0 and Early G1	7	39.4×	1e-08
Cyclin E associated events during G1/S transition	10	36.6×	8e-12
Aberrant regulation of mitotic cell cycle due to RB1 defects	7	36.6×	2e-08
G1/S Transition	12	35.9×	4e-14

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of G1/S transition of mitotic cell cycle	7	25.4×	3e-06
G1/S transition of mitotic cell cycle	12	24.3×	7e-11
regulation of G1/S transition of mitotic cell cycle	7	21.7×	6e-06
DNA damage response, signal transduction by p53 class mediator	5	18.1×	6e-04
cellular senescence	6	17.9×	1e-04
positive regulation of fibroblast proliferation	5	14.9×	1e-03
negative regulation of epithelial cell proliferation	5	14.7×	1e-03
cellular response to xenobiotic stimulus	6	14.6×	3e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

CDK6, along with its partner CDK4, are key players in cell cycle progression. The complex has been implicated in a number of cancer types, and is the focus of therapeutic research and development. One targeted therapy for CDK inhibition is palbociclib, which may slow the growth of advanced stage breast cancers. It has also been shown, in mouse, that CDK inhibition may sensitize mutant PIK3CA tumors to PI3K inhibitors.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	12
Likely benign	11
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
157508	NM_001145306.2(CDK6):c.589G>A (p.Ala197Thr)	Pathogenic

SpliceAI

2308 predictions. Top by Δscore:

Variant	Effect	Δscore
7:92615282:CACTT:C	acceptor_gain	1.0000
7:92615284:CTT:C	acceptor_gain	1.0000
7:92615287:C:CC	acceptor_gain	1.0000
7:92618065:AACTT:A	donor_loss	1.0000
7:92618069:TACCA:T	donor_loss	1.0000
7:92618070:A:AC	donor_gain	1.0000
7:92618070:A:AG	donor_loss	1.0000
7:92618071:C:CT	donor_gain	1.0000
7:92618203:TCACG:T	acceptor_gain	1.0000
7:92618204:CACG:C	acceptor_gain	1.0000
7:92618204:CACGC:C	acceptor_gain	1.0000
7:92618205:ACG:A	acceptor_gain	1.0000
7:92618206:CG:C	acceptor_gain	1.0000
7:92618206:CGC:C	acceptor_gain	1.0000
7:92618206:CGCTA:C	acceptor_loss	1.0000
7:92618208:C:CC	acceptor_gain	1.0000
7:92618208:C:CG	acceptor_loss	1.0000
7:92623034:A:AC	donor_gain	1.0000
7:92623034:ACT:A	donor_gain	1.0000
7:92623035:C:CC	donor_gain	1.0000
7:92623035:CT:C	donor_gain	1.0000
7:92623035:CTC:C	donor_gain	1.0000
7:92671424:A:AC	donor_gain	1.0000
7:92671425:C:CC	donor_gain	1.0000
7:92671425:CTTT:C	donor_gain	1.0000
7:92722037:T:C	acceptor_gain	1.0000
7:92725619:CACT:C	donor_loss	1.0000
7:92725620:A:AC	donor_gain	1.0000
7:92725621:C:CC	donor_gain	1.0000
7:92725622:TCA:T	donor_loss	1.0000

AlphaMissense

2126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:92615257:T:A	R288S	1.000
7:92615257:T:G	R288S	1.000
7:92618179:A:G	W243R	1.000
7:92618179:A:T	W243R	1.000
7:92671450:A:T	I208K	1.000
7:92671452:G:C	C207W	1.000
7:92671456:C:T	G206D	1.000
7:92671466:A:G	W203R	1.000
7:92671466:A:T	W203R	1.000
7:92671510:G:T	P188H	1.000
7:92671516:C:G	R186T	1.000
7:92671520:A:G	Y185H	1.000
7:92671523:A:G	W184R	1.000
7:92671523:A:T	W184R	1.000
7:92725633:G:A	T177I	1.000
7:92725666:A:G	L166P	1.000
7:92725670:C:G	G165R	1.000
7:92725674:G:C	D163E	1.000
7:92725674:G:T	D163E	1.000
7:92725675:T:A	D163V	1.000
7:92725675:T:C	D163G	1.000
7:92725675:T:G	D163A	1.000
7:92725676:C:G	D163H	1.000
7:92725678:G:T	A162D	1.000
7:92725683:T:A	K160N	1.000
7:92725683:T:G	K160N	1.000
7:92725708:A:G	L152P	1.000
7:92725708:A:T	L152Q	1.000
7:92725713:G:C	N150K	1.000
7:92725713:G:T	N150K	1.000

dbSNP variants (sampled 300 via entrez): RS10 (7:92754574 A>C,G,T), RS1000035786 (7:92828536 T>C), RS1000063899 (7:92831890 A>C), RS1000070733 (7:92815062 A>G), RS1000087792 (7:92734809 T>C), RS1000094079 (7:92630800 G>A), RS1000109158 (7:92832812 G>A), RS1000110138 (7:92724353 C>T), RS1000124176 (7:92606239 T>C), RS1000135267 (7:92769592 T>C), RS1000139668 (7:92779814 A>G), RS1000163241 (7:92648573 A>G), RS1000165417 (7:92789358 A>G), RS1000184546 (7:92606217 A>G), RS1000191211 (7:92739665 G>T)

Disease associations

OMIM: gene MIM:603368 | disease phenotypes: MIM:109650, MIM:616080

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive primary microcephaly	Supportive	Autosomal recessive
microcephaly 12, primary, autosomal recessive	Limited	Unknown

Mondo (3): Behcet disease (MONDO:0007191), microcephaly 12, primary, autosomal recessive (MONDO:0014484), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (2): Behçet disease (Orphanet:117), Autosomal recessive primary microcephaly (Orphanet:2512)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000582	Upslanted palpebral fissure
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0002119	Ventriculomegaly
HP:0002282	Gray matter heterotopia
HP:0003103	Abnormal cortical bone morphology
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0007333	Hypoplasia of the frontal lobes
HP:0009879	Simplified gyral pattern
HP:0010864	Severe intellectual disability
HP:0011451	Primary microcephaly

GWAS associations

132 associations (top):

Study	Trait	p-value
GCST000174_19	Height	8.000000e-23
GCST000175_12	Height	1.000000e-08
GCST000176_2	Height	4.000000e-07
GCST000232_2	Rheumatoid arthritis	4.000000e-06
GCST000372_4	Height	1.000000e-08
GCST000589_2	White blood cell count	2.000000e-08
GCST000817_117	Height	8.000000e-47
GCST001133_1	White blood cell count	4.000000e-07
GCST001134_15	White blood cell types	7.000000e-10
GCST001956_3	Height	1.000000e-28
GCST002318_136	Rheumatoid arthritis	1.000000e-08
GCST002318_7	Rheumatoid arthritis	5.000000e-09
GCST002556_11	White blood cell count	9.000000e-11
GCST002557_4	Neutrophil count	9.000000e-06
GCST002647_70	Height	4.000000e-88
GCST004067_179	Hip circumference adjusted for BMI	2.000000e-09
GCST004067_196	Hip circumference adjusted for BMI	2.000000e-13
GCST004067_84	Hip circumference adjusted for BMI	8.000000e-20
GCST004500_127	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-10
GCST004501_12	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-09
GCST004504_17	Waist circumference adjusted for BMI in non-smokers	5.000000e-09
GCST004602_55	Mean corpuscular volume	5.000000e-09
GCST004606_160	Eosinophil count	4.000000e-09
GCST004606_161	Eosinophil count	2.000000e-18
GCST004608_99	Granulocyte percentage of myeloid white cells	2.000000e-28
GCST004609_40	Monocyte percentage of white cells	6.000000e-28
GCST004610_160	White blood cell count	1.000000e-14
GCST004610_161	White blood cell count	2.000000e-65
GCST004613_112	Sum neutrophil eosinophil counts	2.000000e-19
GCST004613_113	Sum neutrophil eosinophil counts	4.000000e-64

EFO canonical traits (30, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0005763	pulse pressure measurement
EFO:0004574	total cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004341	body fat distribution
EFO:0004338	body weight
EFO:0004344	birth weight
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0007992	basophil percentage of leukocytes
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004587	lymphocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001528	Behcet Syndrome	C07.465.075; C11.941.879.780.880.200; C14.907.940.100; C16.320.382.250; C17.800.827.368.250; C17.800.862.150
C579935	Autosomal Recessive Primary Microcephaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (14): CHEMBL2111448 (PROTEIN COMPLEX), CHEMBL2111455 (PROTEIN COMPLEX), CHEMBL2508 (SINGLE PROTEIN), CHEMBL3301386 (PROTEIN COMPLEX), CHEMBL3559691 (PROTEIN FAMILY), CHEMBL3885553 (PROTEIN FAMILY), CHEMBL4523700 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523716 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523718 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523739 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

45 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 260,476 (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
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL3894860	TRILACICLIB	4	2,086
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL3904602	LEROCICLIB	3	1,012
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL4802161	DALPICICLIB	3	423
CHEMBL50	QUERCETIN	3	74,559
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL3545283	RIVICICLIB	2	968
CHEMBL4067549	ULECACICLIB	2	41
CHEMBL4277900	CROZBACICLIB	2	18
CHEMBL4446357	EBVACICLIB	2	599
CHEMBL445813	AT-7519	2	2,614
CHEMBL5187755	ATIRMOCICLIB	2
CHEMBL14762	SELICICLIB	2
CHEMBL3115681	NARAZACICLIB	2
CHEMBL5095060	ECIRUCICLIB	2
CHEMBL5095094	CULMERCICLIB	2
CHEMBL5199065	ISTISOCICLIB	2
CHEMBL5201870	TEGTOCICLIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL31574	FISETIN	2
CHEMBL384304	RG-547	2

Clinical evidence (CIViC)

Drug × variant × indication: 5 predictive associations from 5 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
CDK6 Overexpression	Palbociclib	Breast Cancer	Sensitivity/Response	CIViC B	EID11200
CDK6 Overexpression	Fulvestrant	Estrogen-receptor Positive Breast Cancer	Resistance	CIViC B	EID1526
CDK6 EXPRESSION	Dexamethasone + Ribociclib	Childhood B-cell Acute Lymphoblastic Leukemia	Sensitivity/Response	CIViC D	EID7801
CDK6 Overexpression	Fulvestrant + Palbociclib	Estrogen-receptor Positive Breast Cancer	Sensitivity/Response	CIViC D	EID1527
CDK6 Overexpression	Palbociclib	Glioblastoma Proneural Subtype	Sensitivity/Response	CIViC D	EID7800

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CDK4 subfamily

Most potent curated ligand interactions (26 total), top 25:

Ligand	Action	Affinity	Parameter
PF-06873600	Inhibition	10.1	pKi
culmerciclib	Inhibition	9.28	pIC50
crozbaciclib	Inhibition	9.0	pIC50
inixaciclib	Inhibition	9.0	pIC50
trilaciclib	Inhibition	8.4	pIC50
lerociclib	Inhibition	8.33	pIC50
dalpiciclib	Inhibition	8.22	pIC50
cimpuciclib	Inhibition	8.02	pIC50
narazaciclib	Inhibition	8.01	pIC50
vustanaciclib	Inhibition	8.0	pIC50
abemaciclib	Inhibition	8.0	pIC50
BSJ-03-204	Inhibition	7.98	pIC50
atirmociclib	Inhibition	7.86	pKi
ulecaciclib	Inhibition	7.85	pKi
PRT3645	Inhibition	7.7	pIC50
tibremciclib	Inhibition	7.66	pIC50
BSJ-04-132	Inhibition	7.52	pIC50
tanuxiciclib	Inhibition	7.47	pIC50
palbociclib	Inhibition	7.44	pIC50
BSJ-03-123	Inhibition	7.42	pIC50
RGB-286638	Inhibition	7.26	pIC50
bireociclib	Inhibition	7.25	pIC50
AT-7519	Inhibition	6.77	pIC50
voruciclib	Inhibition	6.68	pIC50
CP-10	Inhibition	6.58	pIC50

Binding affinities (BindingDB)

535 measured of 548 human assays (650 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-({6-(2-hydroxyethyl)-8-[(1R,2S)-2-methylcyclopentyl]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl}amino)-N-methylpiperidine-1-sulfonamide	KI	0.06 nM	US-10233188: CDK2/4/6 inhibitors
6-methyl-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.06 nM	US-10233188: CDK2/4/6 inhibitors
6-(2-hydroxyethyl)-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 187	KI	0.08 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
N-methyl-4-[[8-[(1R,2S)-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1-methylpyrazol-4-yl)sulfonylpiperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-ethylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
BDBM467191	KI	0.1 nM	US-10233188: CDK2/4/6 inhibitors
6-(2-hydroxyethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.11 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(2-methoxyethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2S)-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
US10233188, Example 201	KI	0.12 nM	US-10233188: CDK2/4/6 inhibitors
8-cyclopentyl-N-(2-piperazin-1-ylpyrimidin-5-yl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.13 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
US10233188, Example 221	KI	0.13 nM	US-10233188: CDK2/4/6 inhibitors
N-(2,2-difluoropropyl)-4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.14 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(1,1-dioxothiolan-3-yl)sulfonylpiperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.14 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.15 nM	US-10233188: CDK2/4/6 inhibitors
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)-piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(2-methoxyethylsulfonyl)piperidin-4-yl]amino]-6-methylpyrido[2,3-d]pyrimidin-7-one	KI	0.17 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.17 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cyclopentyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.19 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-cyclopropylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
N-(2,2-difluoropropyl)-4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]piperidine-1-sulfonamide	KI	0.21 nM	US-10233188: CDK2/4/6 inhibitors
2-[(1-ethylsulfonylpiperidin-4-yl)amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.21 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cyclopentyl-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.22 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-(oxan-4-yl)piperidine-1-sulfonamide	KI	0.24 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-[[(2R)-oxolan-2-yl]methyl]piperidine-1-sulfonamide	KI	0.24 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(1,1-dioxothiolan-3-yl)sulfonylpiperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1,3-thiazol-2-ylsulfonyl)piperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[1-(1,3,4-thiadiazol-2-ylsulfonyl)piperidin-4-yl]amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.25 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,3R)-3-hydroxycyclohexyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]-amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.26 nM	US-10233188: CDK2/4/6 inhibitors
6-chloro-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
2-[8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetamide	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
6-(hydroxymethyl)-8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
2-[[1-(fluoromethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-[[(2S)-oxolan-2-yl]methyl]piperidine-1-sulfonamide	KI	0.27 nM	US-10233188: CDK2/4/6 inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.28 nM	US-10233188: CDK2/4/6 inhibitors
4-[(8-cycloheptyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]piperidine-1-sulfonamide	KI	0.29 nM	US-10233188: CDK2/4/6 inhibitors
8-phenyl-N-(4-piperazin-1-ylphenyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.32 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
4-[[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-(2-methoxy-2-methylpropyl)piperidine-1-sulfonamide	KI	0.33 nM	US-10233188: CDK2/4/6 inhibitors

ChEMBL bioactivities

2731 potent at pChembl≥5 of 2796 total, top 42 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	Ki	0.06	nM	CHEMBL5817327
10.19	Ki	0.064	nM	CHEMBL5281860
10.10	Ki	0.08	nM	EBVACICLIB
10.10	Ki	0.08	nM	CHEMBL5994083
10.00	IC50	0.1	nM	CHEMBL5762122
9.96	Ki	0.11	nM	EBVACICLIB
9.96	Ki	0.11	nM	CHEMBL5833205
9.92	Ki	0.12	nM	CHEMBL5774115
9.89	Ki	0.13	nM	CHEMBL4750658
9.89	Ki	0.13	nM	CHEMBL5746772
9.89	Ki	0.13	nM	CHEMBL5281770
9.89	Ki	0.13	nM	CHEMBL6047972
9.89	Ki	0.13	nM	CHEMBL5281860
9.85	Ki	0.14	nM	CHEMBL5764489
9.85	Ki	0.14	nM	CHEMBL5866256
9.82	Ki	0.15	nM	CHEMBL5789495
9.80	Ki	0.16	nM	EBVACICLIB
9.77	Ki	0.17	nM	CHEMBL5857212
9.74	Ki	0.18	nM	CHEMBL4745424
9.74	Ki	0.18	nM	CHEMBL5942490
9.72	Ki	0.19	nM	CHEMBL5269912
9.72	Ki	0.19	nM	CHEMBL5833205
9.70	Ki	0.2	nM	PALBOCICLIB
9.70	Ki	0.2	nM	CHEMBL5280928
9.70	IC50	0.2	nM	CHEMBL5970111
9.70	IC50	0.2	nM	CHEMBL5751717
9.68	Ki	0.21	nM	CHEMBL5926192
9.64	Ki	0.23	nM	CHEMBL5790162
9.64	Ki	0.23	nM	CHEMBL5964436
9.62	Ki	0.24	nM	CHEMBL5278622
9.62	Ki	0.24	nM	CHEMBL5847372
9.60	Ki	0.25	nM	CHEMBL5271753
9.59	Ki	0.26	nM	PALBOCICLIB
9.59	Ki	0.26	nM	CHEMBL5278622
9.59	Ki	0.26	nM	CHEMBL5793277
9.57	Ki	0.27	nM	CHEMBL5752026
9.55	Ki	0.28	nM	CHEMBL6042439
9.54	Ki	0.29	nM	CHEMBL5963572
9.53	Kd	0.296	nM	CHEMBL5653589
9.52	Ki	0.3	nM	CHEMBL5287843
9.52	IC50	0.3	nM	CHEMBL5882717
9.51	Ki	0.31	nM	CHEMBL4796501

PubChem BioAssay actives

709 with measured affinity, of 2434 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-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685180: Inhibition of non-phosphorylated CDK6/Cyclin D1 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
6-(2,2-difluoroethyl)-8-[(1S,2S)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685180: Inhibition of non-phosphorylated CDK6/Cyclin D1 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0001	uM
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	1685180: Inhibition of non-phosphorylated CDK6/Cyclin D1 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
8-cyclopentyl-6-(hydroxymethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
6-acetyl-8-cyclopentyl-5-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
Palbociclib	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148051: Binding affinity to human CDK6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0003	uM
2-[8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0003	uM
8-cyclopentyl-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0003	uM
6-chloro-8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685180: Inhibition of non-phosphorylated CDK6/Cyclin D1 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-(5-piperidin-4-yl-2-pyridinyl)pyrimidin-2-amine	1402379: Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay	ic50	0.0004	uM
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0004	uM
N-[5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-pyridinyl]-5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-amine	2107974: Inhibition of CDK6/Cyclin D1 (unknown origin)	ic50	0.0004	uM
Abemaciclib	2198996: Inhibition of human CDK6/cyclin D1 preincubated with compound for 20 mins followed by [33P]ATP addition and measured after 2 hrs by filter binding method	ic50	0.0004	uM
5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	2107974: Inhibition of CDK6/Cyclin D1 (unknown origin)	ic50	0.0005	uM
5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)-N-(5-piperidin-4-yl-2-pyridinyl)pyrimidin-2-amine	2107974: Inhibition of CDK6/Cyclin D1 (unknown origin)	ic50	0.0005	uM
2-[4-[6-[[5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)pyrimidin-2-yl]amino]-3-pyridinyl]piperidin-1-yl]ethanol	1402379: Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay	ic50	0.0005	uM
[4-[6-[[5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]amino]-3-pyridinyl]piperazin-2-yl]methanol	2107974: Inhibition of CDK6/Cyclin D1 (unknown origin)	ic50	0.0007	uM
8-[(1R,2S,3R)-3-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685180: Inhibition of non-phosphorylated CDK6/Cyclin D1 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0008	uM
N-[5-[(4-ethylpiperazin-1-yl)methyl]-2-pyridinyl]-5-fluoro-4-(5-fluoro-1,1-dimethyl-2,3-dihydropyrrolo[1,2-a]benzimidazol-7-yl)pyrimidin-2-amine	1374355: Inhibition of recombinant human full length CDK6 expressed in baculovirus infected Sf9 insect cells using histone H1 substrate after 90 mins by ADP-Glo assay	ic50	0.0009	uM
8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0009	uM
2-[[1-(cyclopropylmethylsulfonyl)piperidin-4-yl]amino]-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]pyrido[2,3-d]pyrimidin-7-one	1685180: Inhibition of non-phosphorylated CDK6/Cyclin D1 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0009	uM
8-cyclopentyl-6-(2-hydroxyethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0009	uM
N-[5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-pyridinyl]-5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-amine	2107974: Inhibition of CDK6/Cyclin D1 (unknown origin)	ic50	0.0009	uM
8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]-6-(propan-2-yloxymethyl)pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0009	uM
5-fluoro-4-(7’-fluoro-2’-methylspiro[cyclopentane-1,3’-indole]-5’-yl)-N-[5-(1-methylpiperidin-4-yl)-2-pyridinyl]pyrimidin-2-amine	1402379: Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay	ic50	0.0010	uM
4-(3-ethyl-7-fluoro-2,3-dimethylindol-5-yl)-5-fluoro-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]pyrimidin-2-amine	1402379: Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay	ic50	0.0010	uM
4-[[6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	1685180: Inhibition of non-phosphorylated CDK6/Cyclin D1 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0010	uM
6-[2-(dimethylamino)ethyl]-N-[5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine	1509615: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay	ic50	0.0011	uM
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0011	uM
8-cycloheptyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0012	uM
8-butan-2-yl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0012	uM
8-cyclohexyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0013	uM
8-cyclopentyl-6-(cyclopropyloxymethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0014	uM
N-[4-[3-(1-cyclopropylethyl)-7-fluoro-2-methylbenzimidazol-5-yl]-5-fluoropyrimidin-2-yl]-6-[2-(dimethylamino)ethyl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine	1509615: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay	ic50	0.0015	uM
6-[2-(dimethylamino)ethyl]-N-[5-fluoro-4-(7-fluoro-2-methyl-3-pentan-3-ylbenzimidazol-5-yl)pyrimidin-2-yl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine	1509615: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay	ic50	0.0015	uM
5-[(4-ethylpiperazin-1-yl)methyl]-N-[4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)-2-pyridinyl]pyrazin-2-amine	1366690: Inhibition of CDK6 (unknown origin) using U-light as substrate preincubated for 1 hr followed by EDTA addition measured after 1 hr by LANCE Ultra kinase assay	ic50	0.0016	uM
6-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)-N-[5-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]pyrazin-2-yl]pyrimidin-4-amine	1366690: Inhibition of CDK6 (unknown origin) using U-light as substrate preincubated for 1 hr followed by EDTA addition measured after 1 hr by LANCE Ultra kinase assay	ic50	0.0016	uM
5-[(4-ethylpiperazin-1-yl)methyl]-N-[5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)-2-pyridinyl]pyrazin-2-amine	1366690: Inhibition of CDK6 (unknown origin) using U-light as substrate preincubated for 1 hr followed by EDTA addition measured after 1 hr by LANCE Ultra kinase assay	ic50	0.0016	uM
6-(1-ethylpiperidin-4-yl)-N-[5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine	1382364: Inhibition of human CDK6/Cyclin-D3	ic50	0.0016	uM
6-[2-(dimethylamino)ethyl]-N-[5-fluoro-4-[7-fluoro-2-methyl-3-(1-methylcyclopropyl)benzimidazol-5-yl]pyrimidin-2-yl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine	1509615: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay	ic50	0.0016	uM
N-[5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]-6-[2-[methyl(2-trimethylsilylethyl)amino]ethyl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine	1509615: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay	ic50	0.0016	uM
5-fluoro-N-[5-[6-(2-fluoroethyl)-2,6-diazaspiro[3.3]heptan-2-yl]-2-pyridinyl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588589: Inhibition of human full length GST-tagged CDK6 (1 to 326(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0016	uM
1-[2-[2-[[5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]amino]-7,8-dihydro-5H-1,6-naphthyridin-6-yl]ethyl]-1-methylguanidine	1509615: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay	ic50	0.0017	uM
8-cyclopentyl-6-(2-methoxyethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933533: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0017	uM
5-fluoro-N-[5-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-2-pyridinyl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588589: Inhibition of human full length GST-tagged CDK6 (1 to 326(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0017	uM
N-[5-[(4-ethylpiperazin-1-yl)methyl]-2-pyridinyl]-5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-amine	2107974: Inhibition of CDK6/Cyclin D1 (unknown origin)	ic50	0.0018	uM
N-[5-[(4-cyclopentylpiperazin-1-yl)methyl]pyrazin-2-yl]-6-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-4-amine	1366690: Inhibition of CDK6 (unknown origin) using U-light as substrate preincubated for 1 hr followed by EDTA addition measured after 1 hr by LANCE Ultra kinase assay	ic50	0.0018	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects cotreatment, decreases expression, affects binding, decreases reaction, increases reaction	6
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
sodium arsenite	increases reaction, affects cotreatment, increases expression, affects localization, affects binding (+3 more)	5
palbociclib	affects binding, decreases reaction, increases phosphorylation, increases expression	5
trichostatin A	affects cotreatment, increases expression, decreases expression	4
Resveratrol	decreases expression, affects cotreatment, increases expression	4
Arsenic Trioxide	decreases phosphorylation, decreases expression, affects cotreatment, affects expression, affects binding (+2 more)	4
Arsenic	affects methylation, increases expression, affects cotreatment, decreases expression, increases abundance	4
Cisplatin	affects cotreatment, decreases expression, increases reaction	4
Estradiol	decreases expression, increases expression, increases reaction	4
Plant Extracts	affects cotreatment, increases expression, decreases expression	4
abemaciclib	affects binding, decreases reaction, decreases activity	3
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression, decreases reaction	3
indole-3-carbinol	affects binding, decreases reaction, decreases activity, decreases expression, increases expression	3
Panobinostat	affects cotreatment, decreases expression, increases expression	3
Endosulfan	decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
picrasidine I	decreases expression, increases expression	2
arsenite	affects binding, decreases reaction, increases methylation	2
methylparaben	decreases expression	2
3,3’-diindolylmethane	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
perfluorooctane sulfonic acid	increases expression, decreases expression	2
chloropicrin	decreases expression	2
U 0126	affects expression, affects reaction, decreases expression, decreases reaction	2
Dasatinib	affects cotreatment, decreases expression	2
Fulvestrant	affects cotreatment, increases methylation, affects response to substance, affects expression, affects phosphorylation (+1 more)	2
Vorinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2

ChEMBL screening assays

715 unique, capped per target: 691 binding, 24 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1051586	Binding	Inhibition of human CDK6/cyclin D3 assessed as remaining activity at 10 uM	Design, synthesis, and structure-activity relationships of aminopyridine N-oxides, a novel scaffold for the potent and selective inhibition of p38 mitogen activated protein kinase. — J Med Chem
CHEMBL5445020	Functional	Affinity Phenotypic Cellular interaction: (Western Blot assay (Rb phosphorylation at Ser795 in MDA-MB-435 cells)) EUB0001326b CDK6	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1316	J.RT3-T3.5	Cancer cell line	Male
CVCL_B1N4	Abcam HeLa CDK6 KO	Cancer cell line	Female
CVCL_B8DF	Abcam HCT 116 CDK6 KO	Cancer cell line	Male
CVCL_B8TX	Abcam MCF-7 CDK6 KO	Cancer cell line	Female
CVCL_B9FM	Abcam A-549 CDK6 KO	Cancer cell line	Male
CVCL_D8IS	Ubigene HCT 116 CDK6 KO	Cancer cell line	Male
CVCL_D9BP	Ubigene HEK293 CDK6 KO	Transformed cell line	Female
CVCL_D9ZV	Ubigene HeLa CDK6 KO	Cancer cell line	Female
CVCL_SI42	HAP1 CDK6 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05879419	PHASE4	ACTIVE_NOT_RECRUITING	Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases
NCT00995709	PHASE3	COMPLETED	Phase III Study in Refractory Behcet’s Disease
NCT01532570	PHASE3	COMPLETED	Clinical Study of TA-650 in Patients With Behcet’s Disease (BD) With Special Lesions
NCT02307513	PHASE3	COMPLETED	A Phase 3 Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Active Behçet’s Disease
NCT02505568	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of Infliximab in Participant With Moderate-to-Severe Refractory Intestinal Behcet’s Disease
NCT03209219	PHASE3	COMPLETED	Interferon α2a Versus Cyclosporine for Refractory Behçet’s Disease Uveitis
NCT04528082	PHASE3	RECRUITING	Apremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet’s Disease
NCT05767047	PHASE3	RECRUITING	A Study of Apremilast in Children With Oral Ulcers Associated With Behçet’s Disease or Juvenile Psoriatic Arthritis
NCT06145893	PHASE3	RECRUITING	A Study of Efficacy and Safety of Hemay005 Tablets in Patients With Behçet’s Disease
NCT06780462	PHASE3	RECRUITING	Randomized Controlled Multicenter Study Comparing Steroid Therapy Plus Anticoagulants to Steroid Therapy Alone in Deep Venous Thrombosis of Behçet’s Syndrome
NCT06925698	PHASE3	NOT_YET_RECRUITING	Immunosuppressive Therapy Alone Versus Plus Oral Anticoagulation in the Treatment of VT Associated With Behcet’s Disease
NCT00001865	PHASE2	COMPLETED	HAT in Eye Complications of Behcet’s Disease
NCT00483184	PHASE2	COMPLETED	Low Dose Interferon Alpha Treatment for Oral Ulcers of Behcet’s Disease
NCT00664599	PHASE2	COMPLETED	Rituximab for the Treatment of Severe Ocular Manifestations of Behcet’s Disease
NCT00700297	PHASE2	COMPLETED	Colchicine Randomized Double-Blind Controlled Crossover Study in Behcet’s Disease
NCT00866359	PHASE2	COMPLETED	A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
NCT01693653	PHASE2	TERMINATED	Tocilizumab for the Treatment of Behcet’s Syndrome
NCT02648581	PHASE2	COMPLETED	Efficacy and Safety of Ustekinumab, a Human Monoclonal Anti-IL-12/IL-23 Antibody, in Patients With Behçet Disease
NCT02756650	PHASE2	COMPLETED	1 Year of Treatment With Canakinumab in Behçet’s Disease Patients With Neurologic or Vascular Involvement
NCT03554161	PHASE2	TERMINATED	Tocilizumab for the Treatment of Refractory Behcet’s Uveitis
NCT04186559	PHASE2	UNKNOWN	Topical Pentoxifylline Gel on Behcet’s Disease Genital Ulcers
NCT04218565	PHASE2	TERMINATED	Golimumab for the Treatment of Refractory Behcet’s Uveitis
NCT04609397	PHASE2	TERMINATED	A Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease
NCT06386744	PHASE2	COMPLETED	Dusquetide for the Treatment of Behcet’s Disease
NCT06794008	PHASE2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT07080346	PHASE2	COMPLETED	Upadacitinib for Refractory Behcet’s Syndrome
NCT00550498	PHASE1	TERMINATED	Stem Cell Transplantation in Ocular Lesions of Behcet’s Disease
NCT06371417	PHASE1	RECRUITING	Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
NCT06723106	PHASE1	ENROLLING_BY_INVITATION	Phase 1b Long-term Extension Trial of RAY121 in Immunological Diseases (RAINBOW-LTE Trial)
NCT02620618	PHASE1/PHASE2	COMPLETED	Intravitreal Infliximab in Refractory Uveitis in Behcet’s Disease: A Safety and Efficacy Clinical Study
NCT00699985	Not specified	COMPLETED	Psychological Symptoms in Patients With Behcet’s Disease by SCL90-R
NCT00931957	Not specified	UNKNOWN	Etanercept: Single Blind Control Study in Ocular Manifestations of Behcet’s Disease
NCT01584778	Not specified	COMPLETED	Behçet’s Disease and Eosinophil Cationic Protein
NCT01720628	Not specified	COMPLETED	The Relationship Between Serum Levels of Angiogenin, bFGF, VEGF and Ocular Involvement in Patients With Behçet’s Disease
NCT01780363	Not specified	COMPLETED	MEVALONATE KINASE GENE MUTATIONS AND THEIR CLINICAL CORRELATIONS IN BEHÇET’S DISEASE
NCT02020200	Not specified	UNKNOWN	The Effect of Methylphenidate on Cognitive Abilities of Adults With Bipolar Disorder
NCT03264391	Not specified	COMPLETED	Evaluation of Macular Vascular Changes in Behcet’s Disease Using Optical Coherence Tomography Angiography
NCT03274648	Not specified	COMPLETED	Dietary Interventions and Butyrate Production in Behçet’s Patients
NCT03514056	Not specified	COMPLETED	Frequency of Fibromyalgia in Behcet Disease
NCT03747354	Not specified	UNKNOWN	Assessment of Disease Activity in Behcet by Complete Blood Count