CDK4 cyclin dependent kinase 4
ENSG00000135446 · protein coding · Open Targets profile
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. {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:9003781}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- PROTAC
- Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.3541800081729889 (upper bound 0.5631099939346313). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against CDK4 (trilaciclib, ribociclib, palbociclib, abemaciclib, alvocidib, AT-7519, milciclib, UCN-01, roniciclib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Erica MayerDana-Farber Cancer Institute · 3 of 3 trials Phase 2+
- François-Clément BIDARDInstitut Curie (France) · 3 of 3 trials Phase 2+
- Aleix PratHospital Clínic of Barcelona / SOLTI · 2 of 2 trials Phase 2+
- Amy TierstenIcahn School of Medicine at Mount Sinai · 2 of 2 trials Phase 2+
- Angela DeMicheleUniversity of Pennsylvania · 2 of 2 trials Phase 2+
- Antoine ItalianoInstitut Bergonié · 2 of 2 trials Phase 2+
- Antoinette TanWake Forest University Health Sciences · 2 of 2 trials Phase 2+
- Evanthia GalanisAlliance Foundation Trials, LLC. · 2 of 2 trials Phase 2+
- Jessica TaoJohns Hopkins University · 2 of 2 trials Phase 2+
- Jin ZhouWest China Hospital · 2 of 2 trials Phase 2+
- Joanne MortimerCity of Hope Medical Center · 2 of 2 trials Phase 2+
- Lisa A CareyUNC Lineberger Comprehensive Cancer Center · 2 of 2 trials Phase 2+
- Mark DicksonMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Nadia HarbeckLudwigs-Maximilians-University Munich, Breast Cancer Centre · 2 of 2 trials Phase 2+
- Oleg GluzBreast Centre, Evang. Bethesda-Hospital Moenchengladbach Germany · 2 of 2 trials Phase 2+
Registry trials of trilaciclib, ribociclib, palbociclib, abemaciclib, alvocidib, AT-7519, milciclib, UCN-01, roniciclib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 250 of 376 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 24 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
134 trials of drugs against CDK4 were stopped early; 13 give no reason
Terminated, withdrawn and suspended interventional trials of trilaciclib, ribociclib, palbociclib, abemaciclib, alvocidib, AT-7519, milciclib, UCN-01, roniciclib, AZD-5438, RGB-286638, PHA-793887, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 134.
- terminated · 2026-11-02 · Mayo Clinic · Abemaciclib“The primary biomarker (CD8/FOXP3) was rarely observed to be < 1.6 in residual tumors examined in first stage of study.”
- terminated · 2026-10-27 · Pfizer · Ribociclib“Enrollment was permanently closed for strategic business reasons after 20 participants enrolled in Ph 1b. The decision was not related to safety, efficacy, benefit-risk, or participant welfare. The planned Ph 2 and DDI components were not initiated.”
- terminated · 2026-10-21 · Novartis Pharmaceuticals · Ribociclib“Business reasons and not based on any safety concerns.”
- terminated · 2026-10-15 · Praful Ravi, MB BCHir, MRCP · Abemaciclib“The trial was intended to be Phase 1/2 but did not move forward to Phase 2 since the company providing drug and funding (Lilly) withdrew support for the trial based on data relating to abemaciclib in advanced prostate cancer.”
- terminated · 2026-10-14 · UNICANCER · Ribociclib“poor accrual”
- terminated · 2026-09-24 · Tvardi Therapeutics, Incorporated · Palbociclib, ribociclib“The study was terminated prior to Phase 2 due to slow accrual.”
- terminated · 2026-09-04 · University of Utah · Ribociclib“No accrual in one year”
- terminated · 2026-07-22 · M.D. Anderson Cancer Center · Palbociclib“<75% participation”
- terminated · 2026-07-10 · Novartis Pharmaceuticals · Ribociclib“Novartis terminated the trial early because the collected data were sufficient to perform the analysis stated for the primary endpoint.”
- terminated · 2026-06-26 · Eli Lilly and Company · Abemaciclib“The study was terminated early as related study I3Y-MC-JPCM (NCT03706365) did not meet its primary endpoint.”
- terminated · 2026-06-25 · SOLTI Breast Cancer Research Group · Ribociclib + Letrozole OR Fulvestrant, Palbociclib + Letrozole OR Fulvestrant“The study was prematurely halted because enrollment was significantly delayed compared with the original projections due to the evolving therapeutic landscape.”
- terminated · 2026-05-22 · University of Arizona · Abemaciclib“Standard of care therapy for Stage III-IVA HNSCC updated in June to include neoadjuvant + adjuvant immunotherapy.”
- terminated · 2026-04-28 · OHSU Knight Cancer Institute · Abemaciclib“Loss of support.”
- terminated · 2026-04-22 · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Ribociclib“Sponsor-PI decision. An analysis of the primary endpoint concluded that the addition of ribociclib to standard of care enzalutamide did not demonstrate benefit, an all active subjects were removed from the study.”
- withdrawn · 2026-04-15 · Centre Antoine Lacassagne · Ribociclib Oral Tablet“Sponsor decision due to recruitment default”
- terminated · 2026-03-31 · Criterium, Inc. · Abemaciclib“Study was terminated due to delayed recruitment.”
- terminated · 2026-03-10 · Yael P Mosse · Ribociclib“The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible.”
- terminated · 2026-02-20 · Dana-Farber Cancer Institute · Abemaciclib“Slow accrual”
- suspended · 2026-02-13 · Dana-Farber Cancer Institute · Palbociclib“Funding and drug supply to continue the study are pending.”
- withdrawn · 2026-02-12 · Danish Breast Cancer Cooperative Group · Ribociclib with ET, Abemaciclib with ET“Lack of funding”
- terminated · 2025-11-28 · Blueprint Medicines Corporation · Ribociclib“This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.”
- terminated · 2025-11-24 · Sanofi · Palbociclib, Abemaciclib“Sponsor decision to prematurely stop the study, not linked to any safety concern.”
- terminated · 2025-11-12 · NiKang Therapeutics, Inc. · palbociclib“This study was terminated as a result of Sponsor portfolio reprioritization.”
- terminated · 2025-10-10 · Novartis Pharmaceuticals · Ribociclib“Study halted early due to high toxicity risk (from BHLRM model) in combo treatment and inability to identify recommended Phase 2 dose in initial phase (Phase 1-Part A), making continuation to subsequent phases (Phase 1-Part B and Phase 2) unfeasible.”
- terminated · 2025-09-30 · Novartis Pharmaceuticals · Ribociclib“Business reasons”
Paediatric incentives and obligations for CDK4's drugs
For trilaciclib, ribociclib, palbociclib, abemaciclib, alvocidib, AT-7519, milciclib, UCN-01, roniciclib, AZD-5438, RGB-286638, PHA-793887: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: yes · CDK4 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000241250 (trilaciclib (dihydrochloride), Prevention of chemotherapy-induced myelosuppression in small-cell lung cancer): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 16 May 2025; EMA/PE/0000228776 (abemaciclib, Treatment of glioma): PM: decision on the application for modification of an agreed PIP, 28 Jan 2025; EMEA-002765-PIP02-21-M01 (ribociclib, Treatment of neuroblastoma): PM: decision on the application for modification of an agreed PIP, 17 Jul 2024; EMEA-002342-PIP01-18-M04 (abemaciclib, Treatment of Ewing sarcoma): PM: decision on the application for modification of an agreed PIP, 7 Feb 2024; +6 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/15/1437 positive 12 Feb 2015: Treatment of acute myeloid leukaemia; EU/3/07/485 positive 23 Oct 2007: Treatment of chronic lymphocytic leukaemia; EU/3/12/1059 withdrawn 8 Nov 2012: Treatment of malignant thymomaRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Palbociclib Viatris: authorised since 19 Jun 2026; Zinmyleo: application withdrawn; Verzenios: authorised since 26 Sept 2018; Kisqali: authorised since 22 Aug 2017; +1 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of trilaciclib, ribociclib, palbociclib, abemaciclib, alvocidib, at-7519, milciclib, ucn-01, roniciclib, azd-5438, rgb-286638, pha-793887Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 54 interventional studies of trilaciclib, ribociclib, palbociclib, abemaciclib, alvocidib, at-7519, milciclib, ucn-01, roniciclib, azd-5438, rgb-286638, pha-793887 include patients under 18; 22 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 17 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.