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Protein / target

Cyclin-dependent kinase 6

Encoded byCDK6Q00534Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Cyclin-dependent protein serine/threonine kinase

Strongest disease association

Behcet's Syndrome

Via encoding gene CDK6 · Genetic evidence · score 0.68

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

6 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.

View complete UniProt function annotation

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

CytoplasmNucleusCell projection, ruffleCytoplasm, cytoskeleton, microtubule organizing center, centrosome
Domains and Gene Ontology detail (42)

Domains & features

Protein kinase

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

326 aa · 37 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell-cycle regulationUniProt · GOOncogenic signallingReactomeCell proliferation & survivalGOCell migrationGOKinase signallingUniProt · GOTranscriptional regulationUniProt · GO
View supporting evidence

Cell-cycle regulation

  • ·Serine/threonine-protein kinase involved in the control of the cell cycle and differenti…
  • ·G1/S transition of mitotic cell cycle
  • ·G2/M transition of mitotic cell cycle

Oncogenic signalling

  • ·Oncogene Induced Senescence
  • ·Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Cell migration

  • ·regulation of cell motility

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)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

CCND3CDKN1ACDKN2CCDK4CDKN2BCCNE1CCNL2CDKN2DCCND1CCNA2CDK6

10 strongest partners — larger node and heavier line mean higher confidence

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.

Approved medicines with mapped indications

2 medicines · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Breast Neoplasms2 medicines
Broader indication categories (1)
Neoplasms2 medicines

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

5 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

abemaciclib
Narrow target profileApprovedInhibitor

Cyclin-dependent kinase 6 inhibitor

Indicated for Breast Neoplasms, Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

ribociclib
Narrow target profilePhase 3Inhibitor

Cyclin-dependent kinase 6 inhibitor

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

palbociclib
ApprovedInhibitor

CDK6/cyclin D1 inhibitor

Indicated for Breast Neoplasms, Neoplasms

Acts on a complex — shared with CCND1 · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CDK6

Gene-level evidence surfaced through the gene CDK6that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Breast Neoplasms
0.84Well supported

Clinical evidence dominant · Open Targets 0.62

Small Cell Lung Carcinoma
0.79Well supported

Clinical evidence dominant · Open Targets 0.62

Neoplasms
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.57

Carcinoma, Renal Cell
0.72Moderately supported

Genetic evidence dominant · Open Targets 0.41

Behcet's Syndrome
0.69Moderately supported

Genetic evidence dominant · Open Targets 0.42

View evidence synthesis (5)
Breast NeoplasmsWell supported
0.84
agreement 0.730.95
Clinical64%Somatic mutation26%Literature9%RNA expression1%

Open Targets aggregate 0.62 · 4 independent evidence families

Small Cell Lung CarcinomaWell supported
0.79
agreement 0.670.91
Clinical62%Somatic mutation28%Literature10%

Open Targets aggregate 0.62 · 3 independent evidence families

NeoplasmsModerately supported
0.75
agreement 0.630.87
Clinical65%Somatic mutation20%Literature15%

Open Targets aggregate 0.57 · 3 independent evidence families

Carcinoma, Renal CellModerately supported
0.72
agreement 0.630.81
Genetic55%Somatic mutation30%Clinical13%Literature2%

Open Targets aggregate 0.41 · 4 independent evidence families

Behcet's SyndromeModerately supported
0.69
agreement 0.550.83
Genetic96%Literature4%

Open Targets aggregate 0.42 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Breast Neoplasms0.62
Small Cell Lung Carcinoma0.62
Neoplasms0.57
Autosomal recessive primary microcephaly0.52
Neurodegenerative Diseases0.49
Behcet's Syndrome0.42
Prostate adenocarcinoma0.42
Carcinoma, Renal Cell0.41

Drug development

12 compounds recorded · 5 approved · 7 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
RIBOCICLIBPhase 3
AZD-5438Phase 1
RONICICLIBPhase 2
TRILACICLIB DIHYDROCHLORIDEApproval
PHA-793887Phase 1
ALVOCIDIBPhase 3
ABEMACICLIBApproval
RIBOCICLIB SUCCINATEApproval
TRILACICLIBApproval
UCN-01Phase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (literature and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of catalytic activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via palbociclib · NCT05554367

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-07-22

    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

    Status changed to Terminated · ClinicalTrials.gov · via palbociclib

  2. Trial status changed2026-07-21

    A Phase 1, Open-Label, Multicenter Study of INCB123667 as Monotherapy and in Combination With Anticancer Therapies in Participants With Selected Advanced Solid Tumors

    Status changed to Active, not recruiting · ClinicalTrials.gov · via palbociclib

  3. Indication expanded2026-07-13

    Indication expansion: ABEMACICLIB (NDA208716)

    fda · regulatory · fda · via abemaciclib

  4. Trial status changed2026-07-06

    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

    Status changed to Active, not recruiting · ClinicalTrials.gov · via ribociclib

  5. Indication expanded2026-07-01

    Indication expansion: RIBOCICLIB (NDA209092)

    fda · regulatory · fda · via ribociclib

  6. Indication expanded2026-06-24

    Indication expansion: PALBOCICLIB (NDA207103)

    fda · regulatory · fda · via palbociclib

  7. Indication expanded2026-06-24

    Indication expansion: PALBOCICLIB (NDA212436)

    fda · regulatory · fda · via palbociclib

  8. Regulatory approval2026-06-19

    Approval: Palbociclib Viatris (EMA)

    ema · regulatory · ema · via palbociclib

  9. New publication2024-05-08
    Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3.

    Annals of oncology : official journal of the European Society for Medical Oncology · 2024 · 161 citations · Europe PMC · via abemaciclib

  10. New publication2024-01-02
    Efficacy, safety, and predictive model of Palbociclib in the treatment of HR-positive and HER2-negative metastatic breast cancer.

    BMC cancer · 2024 · 28 citations · Europe PMC · via palbociclib

  11. New publication2023-12-01
    Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2.

    Annals of oncology : official journal of the European Society for Medical Oncology · 2023 · 37 citations · Europe PMC · via abemaciclib

  12. New publication2023-09-01
    Efficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial).

    Journal for immunotherapy of cancer · 2023 · 48 citations · Europe PMC · via abemaciclib

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.

Research activity

6 papers · to 2024

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.

Related family literature

5

Papers about “Cyclin-Dependent Kinases” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.

Nguyen CB · Clinical cancer research : an official journal of the American Association for Cancer Research · 2024

via Cyclin-Dependent Kinases

Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.

Hussain M · The New England journal of medicine · 2020

via Cyclin-Dependent Kinases

Malignant glioma: genetics and biology of a grave matter.

Maher EA · Genes & development · 2001

via Cyclin-Dependent Kinases

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.