CDK2 cyclin dependent kinase 2
ENSG00000123374 · protein coding · Open Targets profile
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:24728993, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). 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). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation (PubMed:24670654). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:24728993, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:28666995, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:41100585, ECO:0000303|PubMed:19238148, ECO:0000303|PubMed:19561645}.
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, High-Quality Pocket, Druggable Family
- PROTAC
- Literature, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.22854000329971313 (upper bound 0.4123600125312805). 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 CDK2 (dinaciclib, alvocidib, seliciclib, UCN-01, milciclib, AT-7519, roniciclib), 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 dinaciclib, alvocidib, seliciclib, UCN-01, milciclib, AT-7519, 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; 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.
34 trials of drugs against CDK2 were stopped early; 15 give no reason
Terminated, withdrawn and suspended interventional trials of dinaciclib, alvocidib, seliciclib, UCN-01, milciclib, AT-7519, roniciclib, zotiraciclib, AZD-5438, BMS-387032, PHA-793887, AG-24322, 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 34.
- 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 · 2017-05-15 · National Cancer Institute (NCI) · UCN-01 (7-hydroxystaurosporine)“IND was withdrawn by CTEP due to low accrual and cost of maintaining the IND.”
- 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 · 2015-03-02 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“Early termination for discouraging results”
- terminated · 2015-02-04 · Merck Sharp & Dohme LLC · matched by the registry's drug synonymsNo reason given
Paediatric incentives and obligations for CDK2's drugs
For dinaciclib, alvocidib, seliciclib, UCN-01, milciclib, AT-7519, roniciclib, zotiraciclib, AZD-5438, BMS-387032, PHA-793887, AG-24322: 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 · CDK2 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: no · No EMA paediatric investigation plan decision names dinaciclib, alvocidib, seliciclib, ucn-01, milciclib, at-7519, roniciclib, zotiraciclib, azd-5438, bms-387032, pha-793887, ag-24322Rule: 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 dinaciclib, alvocidib, seliciclib, ucn-01, milciclib, at-7519, roniciclib, zotiraciclib, azd-5438, bms-387032, pha-793887, ag-24322Rule: 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 dinaciclib, alvocidib, seliciclib, ucn-01, milciclib, at-7519, roniciclib, zotiraciclib, azd-5438, bms-387032, pha-793887, ag-24322Rule: 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 · 9 interventional studies of dinaciclib, alvocidib, seliciclib, ucn-01, milciclib, at-7519, roniciclib, zotiraciclib, azd-5438, bms-387032, pha-793887, ag-24322 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, 2026-11-11
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 14 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.