Protein / target
Cyclin-dependent kinase 6
Protein at a glance
Biological role
Cyclin-dependent protein serine/threonine kinase activity
Primary system
Nervous system
Strongest disease association
Behcet disease
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
5 approved · 7 in clinical development
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from 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 (PubMed:23918663)
Subcellular location
Domains and Gene Ontology detail (42)Hide
Domains & features
Gene Ontology
- Ccentrosome
- Ccyclin D2-CDK6 complex
- Ccyclin-dependent protein kinase holoenzyme complex
- Ccytoplasm
- Ccytosol
- Cnucleoplasm
- Cnucleus
- Cruffle
- FATP binding
- Fcyclin binding
- Fcyclin-dependent protein serine/threonine kinase activity
- FFBXO family protein binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Kinase signalling
- ·Serine/threonine-protein kinase involved in the control of the cell cycle and differenti…
- ·cyclin-dependent protein kinase holoenzyme complex
- ·cyclin-dependent protein serine/threonine kinase activity
- ·protein serine kinase activity
Transcriptional regulation
- ·Serine/threonine-protein kinase involved in the control of the cell cycle and differenti…
- ·regulation of gene expression
View underlying pathways (9)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Cyclin-dependent kinase 6 inhibitor
Appears in clinical studies involving breast cancer, breast neoplasm, neoplasm, breast carcinoma
Cyclin-dependent kinase 6 inhibitor
Appears in clinical studies involving breast cancer, melanoma, hematopoietic and lymphoid cell neoplasm, teratoma
CDK6/cyclin D1 inhibitor
Appears in clinical studies involving breast cancer, breast carcinoma, breast neoplasm, neoplasm
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 674 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 12 total
breast cancer · melanoma · hematopoietic and lymphoid cell neoplasm
small cell lung carcinoma · small cell lung carcinoma · non-small cell lung carcinoma
small cell lung carcinoma
B-cell chronic lymphocytic leukemia · acute myeloid leukemia by FAB classification · non-Hodgkin lymphoma
breast cancer · breast neoplasm · neoplasm
breast cancer · breast neoplasm · neoplasm
small cell lung carcinoma · myelosuppression · triple-negative breast carcinoma
non-small cell lung carcinoma · kidney cancer · renal cell carcinoma
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Trial status changed
Phase I Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib, or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
- Indication expanded
Indication expansion: ABEMACICLIB (NDA208716)
- Trial status changed
PIKture-01: First-in-Human Study of the PI3KαH1047R Mutant-Selective Inhibitor OKI-219 as Monotherapy in Participants With Advanced Solid Tumors and as Part of Combination Therapy in Participants With Advanced Breast Cancer
- Indication expanded
Indication expansion: RIBOCICLIB (NDA209092)
- Indication expanded
Indication expansion: PALBOCICLIB (NDA212436)
- Indication expanded
Indication expansion: PALBOCICLIB (NDA207103)
- Regulatory approval
Approval: Palbociclib Viatris (EMA)
- Indication expanded
Indication expansion: PALBOCICLIB (NDA212436)
- Indication expanded
Indication expansion: PALBOCICLIB (NDA207103)
- Supplemental approval
Supplemental approval: RIBOCICLIB (NDA209092)
- Label change
Label change: RIBOCICLIB (NDA209092)
- Indication expanded
Indication expansion: PALBOCICLIB (NDA212436)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.