CDK1 cyclin dependent kinase 1
ENSG00000170312 · protein coding · Open Targets profile
Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30139873, PubMed:30704899, PubMed:40440427). Phosphorylates PARVA/actopaxin, APC, AMPH, APC, ASB7, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, UHRF1, KAT5, LMNA, LMNB, LBR, MKI67, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RBBP8/CtIP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS, GLI2 and RUNX2 (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19202191, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:22411829, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25012651, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30704899, PubMed:31279575, PubMed:32351706, PubMed:34741373, PubMed:40440427). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (PubMed:18480403, PubMed:20360007). Essential for early stages of embryonic development (PubMed:18480403, PubMed:20360007). During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation (PubMed:18480403, PubMed:20360007, PubMed:2188730, PubMed:2344612, PubMed:30139873). Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis (PubMed:18480403, PubMed:20360007). Phosphorylates KRT5 during prometaphase and metaphase (By similarity). Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity (PubMed:41100585). Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair (PubMed:20360007). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (PubMed:20395957). Catalyzes lamin (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, promoting nuclear envelope breakdown (PubMed:2188730, PubMed:2344612, PubMed:37788673). In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons (PubMed:18356527). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (PubMed:16371510). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (PubMed:20937773). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)- mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (PubMed:32351706). Phosphorylates SKA3 on multiple sites during mitosis which promotes SKA3 binding to the NDC80 complex and anchoring of the SKA complex to kinetochores, to enable stable attachment of mitotic spindle microtubules to kinetochores (PubMed:28479321, PubMed:31804178, PubMed:32491969). {ECO:0000250|UniProtKB:P11440, ECO:0000250|UniProtKB:P39951, ECO:0000269|PubMed:16371510, ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:25012651, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:28479321, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:30723163, ECO:0000269|PubMed:31279575, ECO:0000269|PubMed:31804178, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:32491969, ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:41100585}.
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
- Advanced Clinical, Structure with Ligand, High-Quality Ligand, Druggable Family
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.14464999735355377 (upper bound 0.3041299879550934). 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 7 registry trials, updated in the last three years, of the most advanced drugs against CDK1 (alvocidib, dinaciclib, roniciclib, AT-7519, milciclib, seliciclib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Stephen AnthonySumitomo Pharma America, Inc. · 1 of 2 trials Phase 2+
- Christopher D LaoSWOG Cancer Research Network · 1 of 1 trials Phase 2+
- Gilles RAULTCentre de Pérharidy - Roscoff · 1 of 1 trials Phase 2+
- Ning-Ai LiuCedars-Sinai Medical Center · 1 of 1 trials Phase 2+
- Shlomo MelmedCedars-Sinai Medical Center · 1 of 1 trials Phase 2+
- Geoffrey I ShapiroDana-Farber Cancer Institute · 0 of 1 trials Phase 2+
- Khanh T DoDana-Farber - Harvard Cancer Center LAO · 0 of 1 trials Phase 2+
Registry trials of alvocidib, dinaciclib, roniciclib, AT-7519, milciclib, seliciclib 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; 6 of 7 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. Source: ClinicalTrials.gov, fetched live.
32 trials of drugs against CDK1 were stopped early; 14 give no reason
Terminated, withdrawn and suspended interventional trials of alvocidib, dinaciclib, roniciclib, AT-7519, milciclib, seliciclib, zotiraciclib, RGB-286638, PHA-793887, AG-24322, AZD-5438, RG-547, 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 32.
- terminated · 2026-02-23 · National Cancer Institute (NCI) · Zotiraciclib (TG02)“Unable to supply investigational agent, Zotiraciclib (TG02).”
- terminated · 2025-12-12 · University Hospital, Brest · matched by the registry's drug synonyms“The centers have no longer patients. In September 2018, set up of a competitive international study.”
- terminated · 2023-11-15 · Sumitomo Pharma America, Inc. · Alvocidib“Due to slow enrollment, the extensive time projected to conclude the study hypothesis rendered the study no longer reasonably feasible to complete.”
- terminated · 2023-11-09 · Sumitomo Pharma America, Inc. · Alvocidib (flavopiridol) and cytarabine (Ara-C), Alvocidib (flavopiridol)“Business decision to terminate the development of alvocidib program on 17 November 2020. Patients permitted on treatment until April 22, 2021. The last end-of-treatment follow-up completed on May 14, 2021.”
- terminated · 2023-11-09 · Sumitomo Pharma America, Inc. · Alvocidib Plus Decitabine (during dose escalation only) or Azacitidine“The sponsor decided not to continue the study based on the overall company strategy in AML.”
- terminated · 2022-12-30 · AbbVie · Dinaciclib“Strategic considerations”
- terminated · 2021-12-22 · Cyclacel Pharmaceuticals, Inc. · seliciclibNo reason given
- terminated · 2021-11-04 · Shlomo Melmed, MD · matched by the registry's drug synonyms“NIH grant ended.”
- terminated · 2021-04-08 · Bayer · Roniciclib (BAY1000394)No reason given
- terminated · 2021-03-01 · Merck Sharp & Dohme LLC · dinaciclib“Business Reasons”
- withdrawn · 2020-11-12 · M.D. Anderson Cancer Center · Alvocidib Hydrochloride“The original sponsor was acquired by a new company and has elected to end funding for all Investigator Sponsored Trials (ISTs)”
- terminated · 2019-12-12 · National Cancer Institute (NCI) · Flavopiridol (alvocidib)No reason given
- terminated · 2019-02-06 · Tiziana Life Sciences LTD · Milciclib Maleate“For the last patient still on treated nominal therapeutic use of the Milciclib was approved at INT Milano.”
- terminated · 2019-02-06 · Tiziana Life Sciences LTD · Milciclib Maleate“For the 2 last patients still on treated nominal therapeutic use of the Milciclib was approved at INT Milano.”
- terminated · 2018-06-25 · Bayer · Roniciclib (BAY1000394)No reason given
- terminated · 2017-04-04 · National Cancer Institute (NCI) · dinaciclib“Slow accrual”
- terminated · 2016-10-24 · National Cancer Institute (NCI) · alvocidib“CTEP Initiated Action.”
- withdrawn · 2016-08-10 · Yonsei University · BAY 1000394 (Roniciclib) in combination with docetaxelNo reason given
- terminated · 2016-08-08 · National Cancer Institute (NCI) · alvocidib“Administratively Complete”
- withdrawn · 2016-07-01 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms“Development of BAY1000394 has been terminated by Bayer.”
- terminated · 2015-11-11 · National Cancer Institute (NCI) · Alvocidib HydrochlorideNo reason given
- terminated · 2015-08-07 · Merck Sharp & Dohme LLC · matched by the registry's drug synonymsNo reason given
- terminated · 2015-02-04 · Merck Sharp & Dohme LLC · matched by the registry's drug synonymsNo reason given
- terminated · 2014-02-24 · National Cancer Institute (NCI) · alvocidibNo reason given
- terminated · 2013-12-16 · National Cancer Institute (NCI) · alvocidibNo reason given
Paediatric incentives and obligations for CDK1's drugs
For alvocidib, dinaciclib, roniciclib, AT-7519, milciclib, seliciclib, zotiraciclib, RGB-286638, PHA-793887, AG-24322, AZD-5438, RG-547: 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: no · CDK1 is not on the listRule: 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: no · No EMA paediatric investigation plan decision names alvocidib, dinaciclib, roniciclib, at-7519, milciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, ag-24322, azd-5438, rg-547Rule: 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/3/11/901 withdrawn 27 Sept 2011: 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: no · EMA lists no centrally authorised medicine of alvocidib, dinaciclib, roniciclib, at-7519, milciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, ag-24322, azd-5438, rg-547Rule: 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 alvocidib, dinaciclib, roniciclib, at-7519, milciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, ag-24322, azd-5438, rg-547Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 6 interventional studies of alvocidib, dinaciclib, roniciclib, at-7519, milciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, ag-24322, azd-5438, rg-547 include patients under 18; 1 is 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, 2026-11-12
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 12 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.