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 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 54 total — 1 pathogenic
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈10% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 23
• Drug target: yes — 5 curated mechanism-of-action drugs, 1 via a complex or family; 45 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 3 — Abemaciclib, Ribociclib, Trilaciclib
• Approved drugs acting on a complex or family including it: 1 — Palbociclib (CDK6/cyclin D1)
• 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
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.41 (moderately constrained)
• MANE Select transcript: NM_001145306
• Interaction hub: 3,644 STRING partners (top 1% of genes corpus-wide)

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: 20 — 16 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000424848

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

ENST00000424848, ENST00000265734, ENST00000467166, ENST00000473078, ENST00000491250, ENST00000906279, ENST00000906280, ENST00000906281, ENST00000906282, ENST00000906283, ENST00000930022, ENST00000961497, ENST00000999888, ENST00001106369, ENST00001106370, ENST00001106371, ENST00001106372, ENST00001106373, ENST00001114795, ENST00001139911

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.

Highest expression (Bgee): adrenal tissue, trabecular bone tissue, pylorus, caput epididymis, cardia of stomach.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDK6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	6.5e-05	-0.10	7:92621060:T:A
Testis	eqtl	1.3e-04	-0.18	7:92618762:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.8e-04	+0.23	7:93009469:T:C
Nerve Tibial	eqtl	2.2e-03	-0.15	7:92824368:A:T
Esophagus Gastroesophageal Junction	eqtl	2.4e-03	+0.29	7:93081227:A:G
Pancreas	eqtl	4.6e-02	-0.71	7:93034067:G:A

FANTOM5 promoters

showing 10 of 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

showing 100 of 294 tissues 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
placenta	UBERON:0001987	85.56	gold quality
medial globus pallidus	UBERON:0002477	85.31	gold quality
saphenous vein	UBERON:0007318	85.20	gold quality
stromal cell of endometrium	CL:0002255	84.74	gold quality
globus pallidus	UBERON:0001875	84.60	gold quality
jejunum	UBERON:0002115	84.24	gold quality
ganglionic eminence	UBERON:0004023	83.95	gold quality
eye	UBERON:0000970	83.82	gold quality
superficial temporal artery	UBERON:0001614	83.76	gold quality
corpus callosum	UBERON:0002336	83.46	gold quality
amniotic fluid	UBERON:0000173	83.35	gold quality
palpebral conjunctiva	UBERON:0001812	83.26	gold quality
epithelium of mammary gland	UBERON:0003244	83.01	gold quality
pharyngeal mucosa	UBERON:0000355	82.92	gold quality
urethra	UBERON:0000057	82.90	gold quality
subthalamic nucleus	UBERON:0001906	82.83	gold quality
ventral tegmental area	UBERON:0002691	82.19	gold quality
epithelium of nasopharynx	UBERON:0001951	82.11	gold quality
lower lobe of lung	UBERON:0008949	81.99	gold quality
tonsil	UBERON:0002372	81.42	gold quality
corpus epididymis	UBERON:0004359	81.18	gold quality
bone marrow cell	CL:0002092	80.98	gold quality
islet of Langerhans	UBERON:0000006	80.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.61	gold quality
tongue	UBERON:0001723	80.47	gold quality
germinal epithelium of ovary	UBERON:0001304	80.33	gold quality
penis	UBERON:0000989	80.28	gold quality
heart right ventricle	UBERON:0002080	80.08	gold quality
fundus of stomach	UBERON:0001160	79.92	gold quality
dorsal plus ventral thalamus	UBERON:0001897	79.75	gold quality
duodenum	UBERON:0002114	79.66	gold quality
rectum	UBERON:0001052	79.56	gold quality
right adrenal gland cortex	UBERON:0035827	79.55	gold quality
esophagus squamous epithelium	UBERON:0006920	79.45	gold quality
lateral globus pallidus	UBERON:0002476	79.44	gold quality
endometrium	UBERON:0001295	79.43	gold quality
adrenal gland	UBERON:0002369	79.36	gold quality
superior vestibular nucleus	UBERON:0007227	79.33	gold quality
trigeminal ganglion	UBERON:0001675	78.92	gold quality
right adrenal gland	UBERON:0001233	78.69	gold quality
mammary gland	UBERON:0001911	78.60	gold quality
thoracic mammary gland	UBERON:0005200	78.60	gold quality
adrenal cortex	UBERON:0001235	78.56	gold quality
dorsal root ganglion	UBERON:0000044	78.53	gold quality
stomach	UBERON:0000945	78.53	gold quality
trachea	UBERON:0003126	78.47	gold quality
parietal lobe	UBERON:0001872	78.12	gold quality
postcentral gyrus	UBERON:0002581	78.03	gold quality
seminal vesicle	UBERON:0000998	77.86	gold quality
gingiva	UBERON:0001828	77.54	gold quality
pancreas	UBERON:0001264	77.41	gold quality
left adrenal gland	UBERON:0001234	77.37	gold quality
left adrenal gland cortex	UBERON:0035825	77.13	gold quality
tendon	UBERON:0000043	76.91	gold quality
calcaneal tendon	UBERON:0003701	76.61	gold quality
zone of skin	UBERON:0000014	76.58	gold quality
body of tongue	UBERON:0011876	76.57	gold quality
monocyte	CL:0000576	76.50	gold quality
skin of abdomen	UBERON:0001416	76.48	gold quality
right coronary artery	UBERON:0001625	76.32	gold quality
lymph node	UBERON:0000029	76.28	gold quality
thymus	UBERON:0002370	76.28	silver quality
medulla oblongata	UBERON:0001896	76.21	gold quality
leukocyte	CL:0000738	76.16	gold quality
mononuclear cell	CL:0000842	76.11	gold quality
tendon of biceps brachii	UBERON:0008188	76.06	gold quality
popliteal artery	UBERON:0002250	76.05	gold quality
tibial artery	UBERON:0007610	76.03	gold quality
testis	UBERON:0000473	76.01	gold quality
nasal cavity mucosa	UBERON:0001826	75.85	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	38.3
Bone marrow	tissue	17.1	medium
Placenta	tissue	16.3	high
Cerebellum	tissue	13.2	low
Nucleus accumbens	tissue	12.2
Hippocampal formation	tissue	10.9
Hypothalamus	tissue	9.7
Prefrontal cortex	tissue	9.6
Cerebral cortex	tissue	9.6	low
Motor cortex	tissue	9.6
Insular cortex	tissue	9.6
Substantia nigra	tissue	9.5
Hippocampus	tissue	9.5	not detected
Parathyroid gland	tissue	9.3	medium
Postcentral gyrus	tissue	9.3
Retrosplenial and cingulate cortex	tissue	9.0
Retrosplenial cortex	tissue	8.9
Entorhinal cortex	tissue	8.7
Septum	tissue	8.6
Stomach 1	tissue	8.5	medium
Spinal cord	tissue	8.4
Periaqueductal gray	tissue	8.3
Amygdala	tissue	8.0
Temporal cortex	tissue	8.0
Basal ganglia	tissue	7.9	not detected
Ventral forebrain	tissue	7.9
Superior colliculi	tissue	7.7
Choroid plexus	tissue	7.6
Putamen	tissue	7.4
Locus coeruleus	tissue	7.3
Corpus callosum	tissue	7.1
Rectum	tissue	7.0	medium
Pons	tissue	6.9
Midbrain	tissue	6.8
Small intestine	tissue	6.8	high
Adrenal gland	tissue	6.8	low
Occipital cortex	tissue	6.6
Medulla oblongata	tissue	6.5
Thalamus	tissue	6.5
Somatosensory cortex	tissue	6.2
Skin 1	tissue	6.1	low
Lymph node	tissue	6.1	medium
Pancreas	tissue	5.9	low
Olfactory bulb	tissue	5.9
Tonsil	tissue	5.8	medium
Duodenum	tissue	5.7	high
Colon	tissue	5.5	low
Liver	tissue	5.5	not detected
Breast	tissue	4.6	medium
Spleen	tissue	4.6	low
Cervix	tissue	4.5	low
Appendix	tissue	4.4	medium
Kidney	tissue	4.1	medium
Vagina	tissue	4.0	low
Seminal vesicle	tissue	3.9	low
Lung	tissue	3.8	medium
Urinary bladder	tissue	3.6	low
Esophagus	tissue	3.4	low
Gallbladder	tissue	3.4	medium
Testis	tissue	3.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Centromedial thalamic nucleus (22.4), Temporal white matter (20.2), Area striata (white matter) (18.6), Cerebellar white matter (18.5), Angular gyrus (white matter) (17.4).

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)

Targeting CDK6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 601 miRNAs:

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

gnomAD constraint: pLI 0.997, LOEUF 0.412, missense Z 3.14 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000424848 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈10% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:92,615,143–92,671,437	90 / 136.2	0.66	no
7:92,671,438–92,833,157	82 / 202.1	0.41	no
7:92,833,158–92,833,191	21 / 18.4	1.14	no
7:92,833,192–92,833,280	13 / 43.8	0.30	yes (p 3.2e-06)
7:92,833,281–92,833,323	18 / 18.5	0.97	no
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.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): AML-193 (-2.914), NOMO-1 (-2.726), OCI-LY-19 (-2.683), U-937 (-2.59), DB (-2.569), THP-1 (-2.566), MOLM-13 (-2.51), EPLC-272H (-2.495), M-07e (-2.315), SU-DHL-4 (-2.305), OCI-AML2 (-2.272), OPM-2 (-2.27), LP-1 (-2.232), L-363 (-2.228), EBC-1 (-2.023).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1277162) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 47 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased thymocyte number	2
thymus hypoplasia	2
abnormal T cell differentiation	2
increased mean corpuscular volume	2
decreased double-positive T cell number	2
decreased leukocyte cell number	1
abnormal spleen morphology	1
small spleen	1
spleen hypoplasia	1
abnormal thymus morphology	1
small thymus	1
enlarged thymus	1
increased thymocyte number	1
small superior vagus ganglion	1
decreased body weight	1
reduced female fertility	1
abnormal eye morphology	1
abnormal definitive hematopoiesis	1
abnormal spleen red pulp morphology	1
abnormal hematopoietic system morphology/development	1
abnormal lymphopoiesis	1
abnormal erythrocyte morphology	1
decreased mature ovarian follicle number	1
decreased erythrocyte cell number	1
thymus atrophy	1

+22 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Ovis aries	B2MVY4	100.0%	Diamond
Bos taurus	Q32KY4	100.0%	Diamond
Pongo abelii	Q5RD27	99.4%	Diamond
Saccharomyces cerevisiae YJM789	A6ZQG7	99.2%	Diamond
Saccharomyces cerevisiae S288C	P38970	99.2%	Diamond
Sus scrofa	P79432	99.0%	Diamond
Xenopus tropicalis	A4QNA8	89.7%	Diamond
Xenopus laevis	Q91727	79.0%	Diamond
Caenorhabditis elegans	B3WFY8	68.3%	Diamond
Dictyostelium discoideum	Q54XI9	62.8%	Diamond
Arabidopsis thaliana	Q9LZV4	60.5%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SSH4	44.2%	Diamond
Schizosaccharomyces pombe 972h-	O42900	35.0%	Diamond
Human alphaherpesvirus 1 strain 17	P04413	73.8%	Diamond
Human herpesvirus 2 strain HG52	P13287	73.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CDK6-AS1	ncRNA	101927497
SAMD9	protein-coding	54809
FAM133B	protein-coding	257415
RBM48	protein-coding	84060
SAMD9L	protein-coding	219285
HEPACAM2	protein-coding	253012
PEX1	protein-coding	5189
GATAD1	protein-coding	57798

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)

• 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 (48 total): helix 18, 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 by resolution:

PDB	Title	Method	Resolution (Å)
9PE8	CDK6 to CDK4 active site surrogate in complex with PF-07220060	X-RAY DIFFRACTION	1.8
1BLX	P19INK4D/CDK6 COMPLEX	X-RAY DIFFRACTION	1.9
6OQO	CDK6 in complex with Cpd24 …	X-RAY DIFFRACTION	1.98
9D8U	Crystal structure of CDK6 in complex with atirmociclib	X-RAY DIFFRACTION	2
9PE7	CDK6 to CDK4 active site surrogate in complex with compound 6	X-RAY DIFFRACTION	2.05
5L2S	The X-ray co-crystal structure of human CDK6 and Abemaciclib.	X-RAY DIFFRACTION	2.27
4AUA	Liganded X-ray crystal structure of cyclin dependent kinase 6 (CDK6)	X-RAY DIFFRACTION	2.31
5L2T	The X-ray co-crystal structure of human CDK6 and Ribociclib.	X-RAY DIFFRACTION	2.37
3NUP	CDK6 (monomeric) in complex with inhibitor	X-RAY DIFFRACTION	2.6
3NUX	CDK6 (monomeric) in complex with inhibitor	X-RAY DIFFRACTION	2.7
4EZ5	CDK6 (monomeric) in complex with inhibitor	X-RAY DIFFRACTION	2.7
6OQL	CDK6 in complex with Cpd13 …	X-RAY DIFFRACTION	2.71
5L2I	The X-ray co-crystal structure of human CDK6 and Palbociclib.	X-RAY DIFFRACTION	2.75
8I0M	Structure of CDK6 in complex with inhibitor	X-RAY DIFFRACTION	2.78
1BI8	MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D …	X-RAY DIFFRACTION	2.8
2F2C	X-ray structure of human CDK6-Vcyclinwith the inhibitor aminopurvalanol	X-RAY DIFFRACTION	2.8
1G3N	STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX	X-RAY DIFFRACTION	2.9
1XO2	Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor …	X-RAY DIFFRACTION	2.9
4TTH	Crystal structure of a CDK6/Vcyclin complex with inhibitor bound	X-RAY DIFFRACTION	2.9
2EUF	X-ray structure of human CDK6-Vcyclin in complex with the inhibitor PD0332991	X-RAY DIFFRACTION	3
1JOW	Crystal structure of a complex of human CDK6 and a viral cyclin	X-RAY DIFFRACTION	3.1
1BI7	MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE …	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, CMGC Ser/Thr protein kinases, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
145	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
19–27	ATP
43	ATP

Post-translational modifications (8)

Type	Positions
Phosphothreonine	177, 325, 49, 70
N6-acetyllysine	264
N-acetylmethionine	1
Phosphotyrosine	13, 24

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 28; 11 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

28 pathways:

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

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 (31): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), positive regulation of cell-matrix adhesion (GO:0001954), type B pancreatic cell development (GO:0003323), DNA damage response (GO:0006974), signal transduction (GO:0007165), negative regulation of cell population proliferation (GO:0008285), response to virus (GO:0009615), regulation of gene expression (GO:0010468), astrocyte development (GO:0014002), dentate gyrus development (GO:0021542), lateral ventricle development (GO:0021670), hemopoiesis (GO:0030097), 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), regulation of cell motility (GO:2000145), negative regulation of cellular senescence (GO:2000773), protein phosphorylation (GO:0006468), 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 (8): 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 D2-CDK6 complex (GO:0097132)

Reactome top-level categories

15 top-level categories:

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

showing 60 of 69 GO namespaces:

Category	Terms
cellular anatomical structure	3
mitotic cell cycle	2
mitotic cell cycle phase transition	2
negative regulation of cellular process	2
animal gross anatomical part developmental process	2
negative regulation of cell differentiation	2
regulation of myeloid cell differentiation	2
protein binding	2
protein kinase activity	2
cell cycle G1/S phase transition	1
cell cycle G2/M phase transition	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 population proliferation	1
regulation of cell population proliferation	1
response to other organism	1
gene expression	1
regulation of macromolecule biosynthetic process	1
glial cell development	1
astrocyte differentiation	1
hippocampus development	1
telencephalon development	1
ventricular system development	1
cell development	1
neurogenesis	1
dedifferentiation	1
cellular developmental process	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of developmental process	1
myeloid cell differentiation	1
erythrocyte differentiation	1
negative regulation of myeloid leukocyte differentiation	1
monocyte differentiation	1
regulation of monocyte differentiation	1
osteoblast differentiation	1
regulation of osteoblast differentiation	1
protein serine/threonine kinase activity	1
cyclin-dependent protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion 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
serine/threonine protein kinase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 26 of 50 annotations. The rest are phylogenetic / computational / electronic (IEA).

26 experimentally-supported GO terms:

GO term	NS	Evidence
G1/S transition of mitotic cell cycle	BP	direct assay
cell dedifferentiation	BP	mutant phenotype
gliogenesis	BP	mutant phenotype
negative regulation of cell cycle	BP	direct assay
negative regulation of cellular senescence	BP	direct assay
negative regulation of epithelial cell proliferation	BP	mutant phenotype
negative regulation of monocyte differentiation	BP	direct assay
negative regulation of myeloid cell differentiation	BP	direct assay
negative regulation of osteoblast differentiation	BP	direct assay
positive regulation of cell-matrix adhesion	BP	direct assay
positive regulation of fibroblast proliferation	BP	mutant phenotype
regulation of erythrocyte differentiation	BP	mutant phenotype
regulation of gene expression	BP	direct assay
response to virus	BP	expression pattern
type B pancreatic cell development	BP	direct assay
centrosome	CC	direct assay
cyclin-dependent protein kinase holoenzyme complex	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
ruffle	CC	direct assay
ATP binding	MF	direct assay
FBXO family protein binding	MF	physical interaction
cyclin binding	MF	physical interaction
cyclin-dependent protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,644 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK6	CCNL2	Q96S94	925
CDK6	CCND1	P24385	898
CDK6	CDKN2A	P42771	882
CDK6	CCND3	P30281	867
CDK6	CDKN2C	P42773	862
CDK6	CDKN2B	P42772	861
CDK6	CDKN2D	P55273	841
CDK6	CDK4	P11802	837
CDK6	CDKN1A	P38936	819
CDK6	CDC25A	P30304	795
CDK6	E2F1	Q01094	786
CDK6	CCND2	P30279	785
CDK6	CCNA2	P20248	783
CDK6	CCNA1	P78396	757
CDK6	TP53	P04637	754

IntAct

Human interaction partners of CDK6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 109 partners by confidence:

Partner	Interaction type	MIscore	Records
CCND3	physical association	0.970	25
CDKN2C	physical association	0.970	23
CDKN2D	physical association	0.960	21
CDKN2A	direct interaction	0.950	9
CDKN2B	physical association	0.920	13
CCND1	association	0.880	4
CDC37	physical association	0.730	3
HSP90AB1	physical association	0.720	2
CDKN1B	proximity	0.710	1
CDKN1A	direct interaction	0.690	1
RUNX1	proximity	0.630	5
CALHM5	physical association	0.590	2
SRSF7	phosphorylation reaction	0.570	1
CCNH	physical association	0.560	5
APOBEC1	physical association	0.560	3
CCNI	physical association	0.560	3
OTP	physical association	0.560	3
TRIM15	physical association	0.560	3
CCNT1	association	0.530	4
SMAD4	proximity	0.470	3
BRAF	proximity	0.470	2
FBXW7	proximity	0.470	2
FOXM1	phosphorylation reaction	0.440	2
72	direct interaction	0.440	1
ABI1	phosphorylation reaction	0.440	1
ANKRD12	phosphorylation reaction	0.440	1
ATF6B	phosphorylation reaction	0.440	1
BCL11A	phosphorylation reaction	0.440	1
CASC3	phosphorylation reaction	0.440	1
CBY1	phosphorylation reaction	0.440	1

BioGRID (423 interactions; top human partners by supporting records): CCND3 (Two-hybrid; 29 records), CDKN2A (Affinity Capture-MS; 23 records), CDKN2C (Two-hybrid; 21 records), CCND1 (Affinity Capture-Western; 17 records), CDKN2B (Two-hybrid; 15 records), CDKN2D (Two-hybrid; 12 records), CDKN1B (Co-localization; 11 records), RB1 (Biochemical Activity; 10 records), CDKN1A (Affinity Capture-MS; 9 records), CCND2 (Two-hybrid; 8 records), USP17L2 (Affinity Capture-Western; 7 records), CDC37 (Affinity Capture-Western; 5 records), CDK4 (FRET; 5 records), CDKN1C (Affinity Capture-MS; 5 records), CDK2 (Co-localization; 4 records)

SIGNOR signaling

showing 26 of 34 signaling 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
CDKN2C	down-regulates	CDK6	binding
CDK6	down-regulates	PRDX1	phosphorylation
CDK6	“form complex”	CyclinD3/CDK6	binding

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

Complex	Subunits	Members
★ CyclinD3-CDK4-CDK6-p21 complex	4	CCND3, CDK4, CDK6, CDKN1A
★ CyclinD1-CDK4-CDK6 complex	3	CDK4, CDK6, CCND1
★ CyclinD3-CDK4-CDK6 complex	3	CDK4, CDK6, CCND3
★ CCND1-CDK6 complex	2	CDK6, CCND1
★ CCND2-CDK6 complex	2	CCND2, CDK6
★ CCND3-CDK6 complex	2	CDK6, CCND3
★ AR-CDK6 complex	2	AR, CDK6

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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)	7	52.9×	2e-09
G1 Phase	11	51.6×	1e-14
Regulation of RUNX1 Expression and Activity	5	40.0×	4e-06
FOXO-mediated transcription of cell cycle genes	5	40.0×	4e-06
Cyclin D associated events in G1	14	38.8×	9e-17
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	7	36.6×	3e-08
Mitotic G1 phase and G1/S transition	16	35.1×	3e-18
Cyclin E associated events during G1/S transition	10	34.0×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of G1/S transition of mitotic cell cycle	8	27.3×	2e-07
regulation of G1/S transition of mitotic cell cycle	8	23.3×	4e-07
DNA damage response, signal transduction by p53 class mediator	6	20.5×	4e-05
cellular senescence	7	19.7×	8e-06
positive regulation of miRNA transcription	7	19.4×	8e-06
positive regulation of G1/S transition of mitotic cell cycle	5	19.1×	4e-04
cellular response to xenobiotic stimulus	8	18.3×	2e-06
G1/S transition of mitotic cell cycle	9	17.2×	5e-07

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.

Genetic variants

Variant evidence for CDK6: 54 ClinVar records (1 pathogenic / likely pathogenic); 2 CIViC cancer variants; 132 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
157508	NM_001145306.2(CDK6):c.589G>A (p.Ala197Thr)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CDK6’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 1,208):

Position(s)	Effect	Δscore	Sites
7:92618070–92618071	donor_loss	1.0000	5
7:92618208–92618209	acceptor_loss	1.0000	6
7:92722037	acceptor_gain	1.0000
7:92725624–92725625	donor_loss	1.0000	5
7:92725794–92725795	acceptor_loss	1.0000	6
7:92774694–92774695	donor_loss	1.0000	5
7:92774832–92774833	acceptor_loss	1.0000	5
7:92833089–92833090	donor_loss	1.0000	5
7:92836476–92836477	donor_loss	1.0000	5
7:92614796	donor_gain	0.9900

AlphaMissense

1,193 missense substitutions predicted likely pathogenic (of 2,126 scored), across 247 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M174	9	0.909	0.980
D145	8	1.000	1.000
D163	8	1.000	1.000
N150	8	0.999	1.000
D201	8	0.999	0.999
D104	8	0.997	0.999
H143	8	0.996	0.999
F164	8	0.995	0.999
H137	8	0.994	0.998
F98	8	0.993	0.998
F219	8	0.987	0.999
H73	8	0.979	0.999
S204	8	0.956	0.999
F135	8	0.954	1.000
D81	8	0.941	0.996
D32	8	0.932	0.981
F300	8	0.923	0.995
F209	8	0.921	0.988
D102	8	0.912	0.979
F254	8	0.912	0.990

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	5.59e-06
Pancreatic Adenocarcinoma (TCGA)	unfavorable	7.99e-06
Lung Adenocarcinoma (TCGA)	unfavorable	0.000129

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Severe microcephaly	amber

Mondo (2): microcephaly 12, primary, autosomal recessive (MONDO:0014484), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (1): Autosomal recessive primary microcephaly (Orphanet:2512)

HPO phenotypes

23 phenotypes (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

showing 30 of 132 associations:

Study	Trait	p-value
GCST90002398_104	Neutrophil count	3e-182
GCST90002407_153	White blood cell count	1e-160
GCST90002379_3	Basophil count	1e-141
GCST90002393_548	Monocyte count	6e-136
GCST90000025_1009	Appendicular lean mass	4e-106
GCST90002389_253	Lymphocyte percentage of white cells	2e-89
GCST002647_159	Height	4e-88
GCST004626_125	Myeloid white cell count	3e-73
GCST005973_25	White blood cell count	2e-70
GCST004610_156	White blood cell count	2e-65
GCST004614_125	Granulocyte count	2e-65
GCST90002407_151	White blood cell count	5e-65
GCST004613_132	Sum neutrophil eosinophil counts	4e-64
GCST004620_68	Sum basophil neutrophil counts	5e-60
GCST004625_77	Monocyte count	4e-59
GCST004629_98	Neutrophil count	1e-58
GCST90002380_59	Basophil percentage of white cells	1e-54
GCST90002381_252	Eosinophil count	5e-49
GCST90002379_2	Basophil count	8e-48
GCST000817_90	Height	8e-47
GCST005974_18	Neutrophil count	4e-46
GCST90002399_46	Neutrophil percentage of white cells	3e-44
GCST90002398_103	Neutrophil count	2e-41
GCST90002394_298	Monocyte percentage of white cells	6e-41
GCST010702_8	Subcortical volume (MOSTest)	3e-38
GCST012227_1055	Hip circumference adjusted for BMI	4e-37
GCST90002381_250	Eosinophil count	9e-37
GCST007269_213	Pulse pressure	2e-32
GCST90002389_252	Lymphocyte percentage of white cells	1e-31
GCST90002399_45	Neutrophil percentage of white cells	2e-31

EFO canonical traits (from GWAS)

30 canonical traits:

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

1 disease descriptors:

Descriptor	Name	Tree numbers
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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CDK6 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

5 curated-mechanism drugs:

Drug	Modality	Max phase
ABEMACICLIB	Small molecule	4
RIBOCICLIB	Small molecule	4
TRILACICLIB	Small molecule	4
ALVOCIDIB	Small molecule	3
UCN-01	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes CDK6 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
PALBOCICLIB	CDK6/cyclin D1	2	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 267,444 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

45 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3301610	ABEMACICLIB	4	7,497
CHEMBL3545110	RIBOCICLIB	4	8,501
CHEMBL3894860	TRILACICLIB	4	2,213
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL1078178	MOMELOTINIB	4	3,649
CHEMBL521686	OLAPARIB	4	13,785
CHEMBL189963	PALBOCICLIB	4	13,796
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL4802161	DALPICICLIB	3	469
CHEMBL2103840	DINACICLIB	3	2,395
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL3904602	LEROCICLIB	3	1,068
CHEMBL603469	LESTAURTINIB	3
CHEMBL50	QUERCETIN	3	75,572
CHEMBL445813	AT-7519	2	2,733
CHEMBL495727	AT-9283	2	1,442
CHEMBL5187755	ATIRMOCICLIB	2	53
CHEMBL4277900	CROZBACICLIB	2	20
CHEMBL4297488	CT-7001	2	408
CHEMBL5095094	CULMERCICLIB	2
CHEMBL4446357	EBVACICLIB	2
CHEMBL5095060	ECIRUCICLIB	2
CHEMBL31574	FISETIN	2
CHEMBL1276127	INDIRUBIN	2
CHEMBL5095102	INIXACICLIB	2
CHEMBL5199065	ISTISOCICLIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL3115681	NARAZACICLIB	2
CHEMBL384304	RG-547	2
CHEMBL3545283	RIVICICLIB	2
CHEMBL14762	SELICICLIB	2
CHEMBL5201870	TEGTOCICLIB	2
CHEMBL4067549	ULECACICLIB	2
CHEMBL3905910	VORUCICLIB	2
CHEMBL4462530	ZEMIRCICLIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL488436	AZD-5438	1
CHEMBL296468	BMS-387032	1
CHEMBL482967	CYC-116	1
CHEMBL5834528	INX-315	1
CHEMBL150	KAEMPFEROL	1
CHEMBL4289017	PF-03814735	1
CHEMBL5095191	PF-06842874	1
CHEMBL3545083	RGB-286638	1

Clinical evidence (CIViC)

Drug × variant × indication, from 5 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

5 predictive associations by evidence level:

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	Ribociclib + Dexamethasone	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

CIViC curated variants (2)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

EXPRESSION, Overexpression.

PharmGKB: 1 entry (CPIC guideline: no)

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)

2827 measured of 3759 human assays (3875 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-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.08 nM
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
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
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
(-)-6-(2,2-difluoroethyl)-8-[(1R*,2R*)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.09 nM	US-10800783: 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
(3R,4R)-4-[[5-chloro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(3S,4S)-4-[[5-chloro-4-(5-fluoro-1,1-dimethyl-2,3-dihydropyrrolo[1,2-a]benzimidazol-7-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[4-(4-ethyl-9-fluoro-3,4-dihydro-1H-[1,4]oxazino[4,3-a]benzimidazol-7-yl)-5-fluoropyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[4-[2-(1-aminoethyl)-7-fluoro-3-propan-2-ylbenzimidazol-5-yl]-5-chloropyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[4-(3-tert-butyl-2-methylbenzimidazol-5-yl)-5-fluoropyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(Scheme A-13): (3R,4R)-4-({5-chloro-4-[1-(1,1-difluoropropan-2-yl)-4-fluoro-2-(hydroxymethyl)-1H-benzimidazol-6-yl]pyrimidin-2-yl}amino)-1-(methanesulfonyl)piperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(Scheme A-14): Preparation of (3R,4R)-4-[(5-chloro-4-{4-fluoro-2-[(1R)-1-hydroxyethyl]-1-(propan-2-yl)-1H-benzimidazol-6-yl}pyrimidin-2-yl)amino]-1-(methanesulfonyl)piperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)-2-[[(3R,4R)-3-hydroxy-1-methylsulfonylpiperidin-4-yl]amino]pyrimidine-5-carbonitrile	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-chloro-4-[7-fluoro-2-[(1S)-1-hydroxyethyl]-3-propan-2-ylbenzimidazol-5-yl]-2-pyridinyl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-11220494: Cyclin dependent kinase inhibitors
[(3R,4R)-4-[[4-(3-tert-butyl-7-fluorobenzimidazol-5-yl)-5-chloropyrimidin-2-yl]amino]-3-hydroxypiperidin-1-yl]-(3-fluoroazetidin-3-yl)methanone	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-chloro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)-2-pyridinyl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
US11220494, Example A09	KI	0.1 nM	US-11220494: Cyclin dependent kinase 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
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
(+)-6-(2,2-difluoroethyl)-8-[(1R*,2R*)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.13 nM
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
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
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	KI	0.18 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
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
(3R,4R)-4-[[5-chloro-4-(7-chloro-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-fluoro-4-(9-fluoro-4,4-dimethyl-1,3-dihydro-[1,4]oxazino[4,3-a]benzimidazol-7-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-chloro-4-(7-fluoro-1,1-dimethyl-3,4-dihydro-[1,4]oxazino[4,3-b]indazol-9-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-chloro-4-[7-fluoro-2-(oxetan-3-yl)-3-propan-2-ylbenzimidazol-5-yl]pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(3S,4R)-4-[[5-chloro-4-[3-(1,1-difluoropropan-2-yl)-7-fluoro-2-(1-hydroxyethyl)benzimidazol-5-yl]pyrimidin-2-yl]amino]oxan-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(3S,4R)-4-[[4-[3-tert-butyl-7-fluoro-2-[(1S)-1-hydroxyethyl]benzimidazol-5-yl]-5-chloropyrimidin-2-yl]amino]oxan-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-chloro-4-[7-fluoro-3-(1-methoxypropan-2-yl)-2-methylbenzimidazol-5-yl]pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(3R,4R)-4-[[5-fluoro-4-(2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(Scheme A-9): Preparation of (3R,4R)-4-({4-[1-(azetidin-3-yl)-4-fluoro-2-methyl-1H-benzimidazol-6-yl]-5-fluoropyrimidin-2-yl}amino)-1-(methanesulfonyl)piperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase inhibitors
(Scheme A-12): Preparation of (3R,4R)-4-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazol-6-yl]pyrimidin-2-yl}amino)-1-(methanesulfonyl)piperidin-3-ol	KI	0.2 nM	US-10766884: Cyclin dependent kinase 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

825 with measured affinity, of 2656 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects localization (+3 more)	5
palbociclib	decreases reaction, increases phosphorylation, increases expression, affects binding	5
(+)-JQ1 compound	decreases expression, affects binding, decreases reaction, increases reaction, affects cotreatment	5
trichostatin A	affects cotreatment, increases expression, decreases expression	4
Resveratrol	affects cotreatment, increases expression, decreases expression	4
Arsenic Trioxide	affects binding, increases reaction, decreases activity, decreases phosphorylation, decreases expression (+2 more)	4
Arsenic	decreases expression, increases abundance, affects methylation, increases expression, affects cotreatment	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	increases expression, affects binding, decreases reaction, decreases activity, decreases 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	decreases expression, increases 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

10 cell lines: 8 cancer cell line, 2 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_F5A6	EDITGENE CDK6 Knockout HEK293 Cell Line	Transformed cell line	Female
CVCL_SI42	HAP1 CDK6 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 90 trials:

NCT	Phase	Status	Title
NCT05879419	Phase 4	ACTIVE_NOT_RECRUITING	Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases
NCT00995709	Phase 3	COMPLETED	Phase III Study in Refractory Behcet’s Disease
NCT01532570	Phase 3	COMPLETED	Clinical Study of TA-650 in Patients With Behcet’s Disease (BD) With Special Lesions
NCT02307513	Phase 3	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	Phase 3	COMPLETED	A Study to Evaluate Efficacy and Safety of Infliximab in Participant With Moderate-to-Severe Refractory Intestinal Behcet’s Disease
NCT03209219	Phase 3	COMPLETED	Interferon α2a Versus Cyclosporine for Refractory Behçet’s Disease Uveitis
NCT04528082	Phase 3	RECRUITING	Apremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet’s Disease
NCT05767047	Phase 3	RECRUITING	A Study of Apremilast in Children With Oral Ulcers Associated With Behçet’s Disease or Juvenile Psoriatic Arthritis
NCT06145893	Phase 3	RECRUITING	A Study of Efficacy and Safety of Hemay005 Tablets in Patients With Behçet’s Disease
NCT06780462	Phase 3	RECRUITING	Randomized Controlled Multicenter Study Comparing Steroid Therapy Plus Anticoagulants to Steroid Therapy Alone in Deep Venous Thrombosis of Behçet’s Syndrome
NCT06925698	Phase 3	NOT_YET_RECRUITING	Immunosuppressive Therapy Alone Versus Plus Oral Anticoagulation in the Treatment of VT Associated With Behcet’s Disease
NCT00001865	Phase 2	COMPLETED	HAT in Eye Complications of Behcet’s Disease
NCT00483184	Phase 2	COMPLETED	Low Dose Interferon Alpha Treatment for Oral Ulcers of Behcet’s Disease
NCT00664599	Phase 2	COMPLETED	Rituximab for the Treatment of Severe Ocular Manifestations of Behcet’s Disease
NCT00700297	Phase 2	COMPLETED	Colchicine Randomized Double-Blind Controlled Crossover Study in Behcet’s Disease
NCT00866359	Phase 2	COMPLETED	A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
NCT01693653	Phase 2	TERMINATED	Tocilizumab for the Treatment of Behcet’s Syndrome
NCT02648581	Phase 2	COMPLETED	Efficacy and Safety of Ustekinumab, a Human Monoclonal Anti-IL-12/IL-23 Antibody, in Patients With Behçet Disease
NCT02756650	Phase 2	COMPLETED	1 Year of Treatment With Canakinumab in Behçet’s Disease Patients With Neurologic or Vascular Involvement
NCT03554161	Phase 2	TERMINATED	Tocilizumab for the Treatment of Refractory Behcet’s Uveitis
NCT04186559	Phase 2	UNKNOWN	Topical Pentoxifylline Gel on Behcet’s Disease Genital Ulcers
NCT04218565	Phase 2	TERMINATED	Golimumab for the Treatment of Refractory Behcet’s Uveitis
NCT04609397	Phase 2	TERMINATED	A Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease
NCT06386744	Phase 2	COMPLETED	Dusquetide for the Treatment of Behcet’s Disease
NCT06794008	Phase 2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT07080346	Phase 2	COMPLETED	Upadacitinib for Refractory Behcet’s Syndrome
NCT07634848	Phase 2	WITHDRAWN	Ivarmacitinib for Refractory Behcet’s Syndrome
NCT07833163	Phase 2	NOT_YET_RECRUITING	Corticotropin for Behçet’s Disease: A Multicenter Randomized Controlled TrialAcronym.
NCT00550498	Phase 1	TERMINATED	Stem Cell Transplantation in Ocular Lesions of Behcet’s Disease
NCT06371417	Phase 1	RECRUITING	Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
NCT06723106	Phase 1	ENROLLING_BY_INVITATION	Phase 1b Long-term Extension Trial of RAY121 in Immunological Diseases (RAINBOW-LTE Trial)
NCT02620618	Phase 1/2	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
NCT03771768	Not specified	UNKNOWN	Diode Laser Versus Topical Corticosteroids in Management of Oral Ulcers in Behcet’s Disease
NCT03803462	Not specified	UNKNOWN	Behçet’s Disease Overall Damage Index
NCT03837236	Not specified	UNKNOWN	Inactivity Behavior and Exercise Bariers in Patients With Behçet Disease
NCT03962335	Not specified	COMPLETED	Gut Microbiota and Behcet’s Syndrome: a Dietary Intervention Trial (MAMBA Study)
NCT04101604	Not specified	UNKNOWN	Biomarkers of Common Eye Diseases
NCT04105439	Not specified	UNKNOWN	Plasma Soluble Urokinase Plasminogen Activator Receptor and Behçet’s Disease .
NCT04126850	Not specified	UNKNOWN	Pilot Project: The Amplicon and Metatranscriptomic Study of Intra and Extra Intestinal Microbiome in Non-infectious Uveitis Disease
NCT04334031	Not specified	RECRUITING	Deployment o the Multidisciplinary Prospective Cohort Imminent
NCT04376411	Not specified	COMPLETED	Role of Regulatory B Cells in Behçet’s Disease
NCT04386824	Not specified	COMPLETED	Erectile Dysfunction in Patients With Non Ocular Behçet’s Disease
NCT04402086	Not specified	RECRUITING	Rheumatology Patient Registry and Biorepository
NCT04402255	Not specified	COMPLETED	Pilates Based Exercises in Patients With Behçet and Familial Mediterranean Fever.
NCT04403438	Not specified	COMPLETED	Familial Mediterranean Fever and Behçet: Analysis Before and After Covid19 Pandemic
NCT04530461	Not specified	UNKNOWN	Serologic Profile of SARS CoV2 in COVID-19 Patients With Systemic Diseases
NCT04585360	Not specified	COMPLETED	Psychiatric Manifestations Associated With Behcet’s Disease
NCT04738864	Not specified	UNKNOWN	Neuro-ultrasound Assessment in Behcet’s Disease
NCT04959435	Not specified	COMPLETED	Understanding the Role of Oral Microbiota in Behçet’s Disease (BEHCETBIOT)
NCT04961463	Not specified	COMPLETED	Evaluation of the Psychoeducation Program Given to Behcet’s Patients in the Context of the Roy Adaptation Model

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CDK6 across ~30M SureChEMBL compounds — explore on Sugi Predict.