CDK9 cyclin dependent kinase 9
ENSG00000136807 · protein coding · Open Targets profile
Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245). Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:16427012, PubMed:20930849, PubMed:28426094, PubMed:30134174). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE (PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:16427012, PubMed:20081228, PubMed:20980437, PubMed:21127351, PubMed:9857195). Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling) (PubMed:17956865, PubMed:18362169). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166, PubMed:28539972). Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed:15564463, PubMed:19575011, PubMed:19844166). Also catalyzes phosphorylation of histone H1.4 (H1-4) at 'Ser-187' (H1.4S187Ph), a modification associated with transcription activation (PubMed:28539972). The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351). Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed:20493174). In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:10912001, PubMed:11112772, PubMed:9857195). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245). {ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:19575011, ECO:0000269|PubMed:19844166, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20930849, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:28539972, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:9857195}.
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, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.8726099729537964 (upper bound 1.1617000102996826). 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 CDK9 (alvocidib, dinaciclib, AT-7519, roniciclib, 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, AT-7519, roniciclib, 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.
29 trials of drugs against CDK9 were stopped early; 14 give no reason
Terminated, withdrawn and suspended interventional trials of alvocidib, dinaciclib, AT-7519, roniciclib, seliciclib, zotiraciclib, RGB-286638, PHA-793887, BMS-387032, AZD-5438, 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 29.
- 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 · 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
- terminated · 2013-07-02 · National Cancer Institute (NCI) · alvocidibNo reason given
- terminated · 2013-06-04 · National Cancer Institute (NCI) · alvocidibNo reason given
Paediatric incentives and obligations for CDK9's drugs
For alvocidib, dinaciclib, AT-7519, roniciclib, seliciclib, zotiraciclib, RGB-286638, PHA-793887, BMS-387032, AZD-5438: 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 · CDK9 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 alvocidib, dinaciclib, at-7519, roniciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, bms-387032, azd-5438Rule: 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 leukaemiaRule: 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, at-7519, roniciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, bms-387032, azd-5438Rule: 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, at-7519, roniciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, bms-387032, azd-5438Rule: 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 · 6 interventional studies of alvocidib, dinaciclib, at-7519, roniciclib, seliciclib, zotiraciclib, rgb-286638, pha-793887, bms-387032, azd-5438 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 10 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.