Protein / target

G1/S-specific cyclin-D1

CCND1P24385Homo sapiensSwiss-Prot
UniProt: P24385Ensembl: ENSG00000110092HGNC: HGNC:1582NCBI Gene: 595
Clinically validated
Therapeutic maturity
1
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Protein serine/threonine kinase activator activity

Strongest disease association

AL amyloidosis

Genetic evidence · score 0.81

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Advanced Clinical

Clinical development

1 approved · 1 in clinical development

30 linked trials

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

Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:33854235, PubMed:8114739, PubMed:8302605). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Hypophosphorylates RB1 in early G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8302605). Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity (PubMed:15241418). Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:9106657). Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (PubMed:16569215, PubMed:18417529)

Subcellular location

NucleusCytoplasmNucleus membrane
Domains and Gene Ontology detail (45)

Domains & features

Cyclin N-terminal

Gene Ontology

  • Cbicellular tight junction
  • Ccyclin-dependent protein kinase holoenzyme complex
  • Ccytoplasm
  • Ccytosol
  • Cmicrotubule organizing center
  • Cnuclear membrane
  • Cnucleoplasm
  • Cnucleus
  • Ctranscription repressor complex
  • Fcyclin-dependent protein serine/threonine kinase activator activity
  • Fcyclin-dependent protein serine/threonine kinase regulator activity
  • Fenzyme binding

295 aa · 34 kDa

Biological roles

Reactome v97

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

Transcriptional regulationUniProt · GO · ReactomeKinase signallingUniProt · GOImmune signallingReactomeCell adhesionGO
View supporting evidence

Transcriptional regulation

  • ·Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits…
  • ·transcription repressor complex
  • ·transcription corepressor activity
  • ·DNA-templated transcription

Kinase signalling

  • ·Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits…
  • ·cyclin-dependent protein kinase holoenzyme complex
  • ·protein kinase activity
  • ·protein kinase binding

Immune signalling

  • ·Interleukin-4 and Interleukin-13 signaling

Cell adhesion

  • ·bicellular tight junction
View underlying pathways (18)
SCF(Skp2)-mediated degradation of p27/p21
Pre-NOTCH Transcription and Translation
RMTs methylate histone arginines
Interleukin-4 and Interleukin-13 signaling
Cyclin D associated events in G1
Ubiquitin-dependent degradation of Cyclin D
PTK6 Regulates Cell Cycle
Transcriptional Regulation by VENTX
Transcriptional regulation by RUNX2
Regulation of RUNX1 Expression and Activity
RUNX3 regulates WNT signaling
RUNX3 regulates p14-ARF
Estrogen-dependent gene expression
Estrogen-dependent nuclear events downstream of ESR-membrane signaling
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)

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.

CDK2CDKN1BCDK4CDK6CDKN1ARB1CDK1CDKN2AESR1CDKN1CCCND1

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.

Drugs targeting this protein

1

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.

palbociclib
ApprovedInhibitor

CDK6/cyclin D1 inhibitor

Appears in clinical studies involving breast cancer, breast carcinoma, breast neoplasm, neoplasm

Acts on a complex — shared with CDK6 · 1 of 3 recorded protein targets — narrow recorded profile

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

Translational evidence

Open Targets 26

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.

AL amyloidosis0.81

Genetic · overall 0.50

type 2 diabetes mellitus0.77

Genetic · overall 0.48

diabetes mellitus0.71

Genetic · overall 0.44

prostate carcinoma0.70

Genetic · overall 0.50

plasma cell myeloma0.61

Genetic literature · overall 0.53

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

breast cancer0.97

Clinical · overall 0.66

breast carcinoma0.77

Clinical · overall 0.59

breast neoplasm0.73

Clinical · overall 0.51

neoplasm0.65

Clinical · overall 0.45

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

neurodegenerative disease0.53

Pathway

Show all associations
breast cancer0.66
breast carcinoma0.59
plasma cell myeloma0.53
neurodegenerative disease0.53
breast neoplasm0.51
prostate carcinoma0.50
AL amyloidosis0.50
type 2 diabetes mellitus0.48
neoplasm0.45
diabetes mellitus0.44

Open Targets ranks 2,890 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 · 2 total

PALBOCICLIBApproval

breast cancer · breast carcinoma · breast neoplasm

BRICICLIBPhase 1

Tractability

SM · Advanced ClinicalSM · High-Quality LigandSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Safety liabilities

regulation of transcription factor activitydrug toxicity

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.

A Phase 2 Pilot Feasibility Study of Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive Invasive Breast CarcinomaPHASE2

COMPLETED · via palbociclib · NCT02040857

MATCH Treatment Subprotocol Z1C: Phase II Study of Palbociclib (PD-0332991) in Patients With Tumors With CDK4 or CDK6 AmplificationPHASE2

ACTIVE_NOT_RECRUITING · via palbociclib · NCT06390839

A Randomized Trial of Neratinib, A Pan-ERBB Inhibitor, Alone or in Combination With Palbociclib, a CDK4/6 Inhibitor, in Patients With HER2+ Gynecologic Cancers and Other Solid Tumors: A ComboMATCH Treatment TrialPHASE2

RECRUITING · via palbociclib · NCT06126276

A Phase II Trial to Assess the Activity and Safety of Palbociclib in Patients With Well and Moderately Differentiated Metastatic Pancreatic Neuroendocrine Tumors (pNET)PHASE2

COMPLETED · via palbociclib · NCT02806648

A Phase 1/2, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Preliminary Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of ZB716 as Monotherapy and in Combination With Palbociclib in Patients With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast CancerPHASE1/PHASE2

UNKNOWN · via palbociclib · NCT04669587

Neoadjuvant Biomarker ResearcH Study of Palbociclib Combined With Endocrine Therapy in Estrogen Receptor Positive/HER2 Negative Breast CAncerPHASE2

COMPLETED · via palbociclib · NCT03065621

Show remaining trials (24)
Multicentre, International Neoadjuvant Randomized Double-blind Trial Comparing Fulvestrant® to a Combination of Fulvestrant® and Palbociclib (CDK 4/6 Inhibitor) in Patients With Operable Luminal Breast Cancer Responding to Fulvestrant®PHASE3

COMPLETED · via palbociclib · NCT03447132

Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian CancerPHASE2

COMPLETED · via palbociclib · NCT03936270

A Single-Arm, Prospective, Open Clinical Study of Palbociclib for Backline Treatment of Advanced Hepatocellular CarcinomaNA

RECRUITING · via palbociclib · NCT06478927

An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast CancerPHASE1/PHASE2

TERMINATED · via palbociclib · NCT01823835

Phase I Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor Binimetinib (MEK162) for Patients With Advanced KRAS Mutant Non-Small Cell Lung CancerPHASE1

COMPLETED · via palbociclib · NCT03170206

A Phase I Study of Palbociclib in Combination With Chemotherapy in Pediatric Patients With Relapsed or Refractory Acute Lymphoblastic LeukemiaPHASE1

TERMINATED · via palbociclib · NCT03515200

Palbociclib After CDK and Endocrine Therapy (PACE): A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab for Endocrine Pre-treated ER+/HER2- Metastatic Breast CancerPHASE2

ACTIVE_NOT_RECRUITING · via palbociclib · NCT03147287

A Randomized, Multicenter, Open-label, Phase II Trial to Evaluate the Efficacy and Safety of Palbociclib in Combination With Fulvestrant or Letrozole in Patients With HER2 Negative, ER+ Metastatic Breast CancerPHASE2

COMPLETED · via palbociclib · NCT02491983

Palbociclib Plus Fulvestrant in Women With Hormone Receptor Positive and Human Epidermal Growth Factor Receptor Type 2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination With Hormonal Therapy: a Multicenter, Phase II TrialPHASE2

UNKNOWN · via palbociclib · NCT04318223

A Phase I Study of Avelumab, Palbociclib, and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell CarcinomaPHASE1

ACTIVE_NOT_RECRUITING · via palbociclib · NCT03498378

A Phase II Study of Palbociclib Plus Fulvestrant for Pretreated Patients With ER+/HER2- Metastatic Breast CancerPHASE2

COMPLETED · via palbociclib · NCT02536742

The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and ImmunotherapyPHASE2

UNKNOWN · via palbociclib · NCT04591431

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)PHASE3

RECRUITING · via palbociclib · NCT06380751

A Randomized Study Evaluating the Safety and Effects of the Combination of Palbociclib With Epirubicin and Cyclophosphamide Followed by Paclitaxel as Neoadjuvant Therapy in Triple Negative Breast CancerNA

UNKNOWN · via palbociclib · NCT03756090

A Phase 1 Study of Palbociclib (IND#141416), A CDK 4/6 Inhibitor, in Combination With Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)PHASE1

COMPLETED · via palbociclib · NCT03792256

Phase II Trial of Palbociclib With Fulvestrant in Individuals With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Who Have Progressed on Treatment With Palbociclib and an Aromatase InhibitorPHASE2

ACTIVE_NOT_RECRUITING · via palbociclib · NCT02738866

A Phase I, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0077 as a Single Agent in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Solid Tumors and in Combination With Endocrine and Targeted Therapies in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Breast CancerPHASE1

ACTIVE_NOT_RECRUITING · via palbociclib · NCT03006172

Randomized, Non-comparative Neoadjuvant Phase II Study in Patients With ER+/HER2- Breast Cancer >= 2 cm With Safety Run-in, Assessing Nivolumab + Palbociclib + AnastrozolePHASE2

COMPLETED · via palbociclib · NCT04075604

Biomarker and Tumor Cell Culture-Driven Pilot Trial for Treatment of Recurrent GlioblastomaEARLY_PHASE1

RECRUITING · via palbociclib · NCT05432518

A Phase Ib/II Study of the Mirdametinib in Combination With Palbociclib in Patients With Advanced Dedifferentiated LiposarcomaPHASE1/PHASE2

RECRUITING · via palbociclib · NCT06843967

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 MutationPHASE1

TERMINATED · via palbociclib · NCT03065387

PALbociclib in Advanced Breast Cancer: Therapy INtegrating locorEgional Treatment and Palbociclib in de Novo, Treatment Naive, Stage IV ER+, HER2- Breast Cancer PatientsNA

ACTIVE_NOT_RECRUITING · via palbociclib · NCT03870919

Phase I Dose-Escalation Study of Combination of Gedatolisib (a Dual Inhibitor of PI3-K and mTOR) With Palbociclib and Faslodex in the Neoadjuvant Setting in Previously Untreated Patients With ER+/HER2- Breast CancerPHASE1

UNKNOWN · via palbociclib · NCT02626507

A Phase 2, Randomized, Open-Label Dose Optimization and Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY4064809 Combined With a CDK4/6 Inhibitor and Endocrine Therapy in Adults With HR+, HER2-Advanced Breast Cancer With a PIK3CA Mutation Who Received No Prior Treatment for Advanced Breast Cancer (PIKALO-2)PHASE3

RECRUITING · via palbociclib · NCT07174336

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

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.

breast carcinomaWell supported
0.89
agreement 0.81–0.97
Clinical35%Genetic28%Somatic mutation18%Pathway10%Literature9%RNA expression0%

Open Targets aggregate 0.59 · 6 independent evidence families

breast cancerWell supported
0.86
agreement 0.76–0.97
Clinical56%Genetic32%Literature11%

Open Targets aggregate 0.66 · 3 independent evidence families

plasma cell myelomaWell supported
0.82
agreement 0.73–0.91
Genetic41%Somatic mutation29%Pathway14%Clinical10%Literature6%Genetic literaturedup

Open Targets aggregate 0.53 · 5 independent evidence families · 1 not counted as duplicate

AL amyloidosisWell supported
0.82
agreement 0.68–0.95
Genetic95%Literature6%

Open Targets aggregate 0.50 · 2 independent evidence families

prostate carcinomaWell supported
0.81
agreement 0.70–0.93
Genetic62%Somatic mutation27%Literature11%

Open Targets aggregate 0.50 · 3 independent evidence families

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

38

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  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. Indication expanded2026-06-24

    Indication expansion: PALBOCICLIB (NDA212436)

    fda · regulatory · fda · via palbociclib

  3. Indication expanded2026-06-24

    Indication expansion: PALBOCICLIB (NDA207103)

    fda · regulatory · fda · via palbociclib

  4. Regulatory approval2026-06-19

    Approval: Palbociclib Viatris (EMA)

    ema · regulatory · ema · via palbociclib

  5. Indication expanded2025-09-16

    Indication expansion: PALBOCICLIB (NDA212436)

    fda · regulatory · fda · via palbociclib

  6. Indication expanded2025-09-16

    Indication expansion: PALBOCICLIB (NDA207103)

    fda · regulatory · fda · via palbociclib

  7. Indication expanded2025-04-23

    Indication expansion: PALBOCICLIB (NDA212436)

    fda · regulatory · fda · via palbociclib

  8. Indication expanded2025-04-23

    Indication expansion: PALBOCICLIB (NDA207103)

    fda · regulatory · fda · via palbociclib

  9. Label change2025-03-06

    Label change: PALBOCICLIB (NDA212436)

    fda · regulatory · fda · via palbociclib

  10. Label change2025-03-06

    Label change: PALBOCICLIB (NDA207103)

    fda · regulatory · fda · via palbociclib

  11. Label change2024-12-20

    Label change: PALBOCICLIB (NDA212436)

    fda · regulatory · fda · via palbociclib

  12. Label change2024-12-20

    Label change: PALBOCICLIB (NDA207103)

    fda · regulatory · fda · via palbociclib

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.