Protein / target
Cyclin-dependent kinase 4
Protein at a glance
Biological role
Cyclin-dependent protein serine/threonine kinase activity
Strongest disease association
melanoma, cutaneous malignant, susceptibility to, 3
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
5 approved · 12 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
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex
Subcellular location
Domains and Gene Ontology detail (29)Hide
Domains & features
Gene Ontology
- Cbicellular tight junction
- Cchromatin
- Ccyclin D1-CDK4 complex
- Ccyclin D2-CDK4 complex
- Ccyclin-dependent protein kinase holoenzyme complex
- Ccytoplasm
- Ccytosol
- Cnuclear membrane
- Cnucleolus
- Cnucleoplasm
- Cnucleus
- Ctranscription regulator complex
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit…
- ·transcription regulator complex
- ·regulation of gene expression
- ·regulation of transcription initiation by RNA polymerase II
Kinase signalling
- ·Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit…
- ·cyclin-dependent protein kinase holoenzyme complex
- ·cyclin-dependent protein serine/threonine kinase activity
- ·protein serine kinase activity
Cell adhesion
- ·bicellular tight junction
View underlying pathways (19)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 4/cyclin D1 inhibitor
Appears in clinical studies involving breast cancer, breast carcinoma, breast neoplasm, neoplasm
Cyclin-dependent kinase 4 inhibitor
Appears in clinical studies involving breast cancer, breast neoplasm, neoplasm, breast carcinoma
Cyclin-dependent kinase 4 inhibitor
Appears in clinical studies involving breast cancer, melanoma, hematopoietic and lymphoid cell neoplasm, teratoma
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 1,396 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 · 17 total
mantle cell lymphoma · B-cell chronic lymphocytic leukemia · plasma cell myeloma
thymic carcinoma · thymoma · hepatocellular carcinoma
lymphoid neoplasm
small cell lung carcinoma
breast cancer · breast carcinoma · breast neoplasm
breast cancer · breast neoplasm · neoplasm
breast cancer · melanoma · hematopoietic and lymphoid cell neoplasm
B-cell chronic lymphocytic leukemia · acute myeloid leukemia by FAB classification · non-Hodgkin lymphoma
Tractability
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.
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.