CUL4A cullin 4A
ENSG00000139842 · protein coding · Open Targets profile
Core component of multiple cullin-RING-based E3 ubiquitin- protein ligase complexes which mediate the ubiquitination of target proteins (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620, PubMed:30166453, PubMed:33854232, PubMed:33854239). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620). The E3 ubiquitin- protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DET1-COP1) directs ubiquitination of JUN (PubMed:14739464). DCX(DDB2) directs ubiquitination of XPC (PubMed:15811626). DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition (PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of p53/TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:14578910, PubMed:15448697, PubMed:15548678). DCX(DTL) directs autoubiquitination of DTL (PubMed:23478445). In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip (PubMed:16537899). Is involved in ubiquitination of HOXA9 (PubMed:14609952). The DDB1-CUL4A- DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). The DCX(ERCC8) complex (also named CSA complex) plays a role in transcription-coupled repair (TCR) (PubMed:12732143, PubMed:32355176, PubMed:38316879). A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948). The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3) (PubMed:33854232, PubMed:33854239). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:30166453). With CUL4B, contributes to ribosome biogenesis (PubMed:26711351). {ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:15811626, ECO:0000269|PubMed:16537899, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:24209620, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30166453, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854239}.
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, High-Quality Ligand, High-Quality Pocket
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.1675499975681305 (upper bound 0.2544800043106079). 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 225 registry trials, updated in the last three years, of the most advanced drugs against CUL4A (pomalidomide, iberdomide), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Bristol-Myers SquibbBristol-Myers Squibb · 9 of 14 trials Phase 2+Ph3NCT05519085 · A Study to Evaluate Mezigdomide, Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)brief
- Noa BiranHackensack Meridian Health · 3 of 3 trials Phase 2+
- Xavier LeleuService des maladies du sang, CHRU de Lille · 3 of 3 trials Phase 2+
- Andrew J YeeMassachusetts General Hospital · 2 of 2 trials Phase 2+
- Jin LuPeking University People's Hospital · 2 of 2 trials Phase 2+
- Juan José Lahuerta PalaciosHospital Universitario 12 de Octubre · 2 of 2 trials Phase 2+
- Martin KaiserRoyal Marsden NHS Foundation Trust · 2 of 2 trials Phase 2+
- Mateo Mejia SaldarriagaWeill Medical College of Cornell University · 2 of 2 trials Phase 2+
- Philippe MOREAUMaladies du Sang, CHRU, Hôtel Dieu, NANTES · 2 of 2 trials Phase 2+
- Prashant KapoorMayo Clinic in Rochester · 2 of 2 trials Phase 2+
- Ajay K. NookaEmory University/Winship Cancer Institute · 1 of 1 trials Phase 2+
- Ajay NookaEmory University · 1 of 1 trials Phase 2+
- Amrita KrishnanCity of Hope Medical Center · 1 of 1 trials Phase 2+
- Andrew YeeMassachusetts General Hospital · 1 of 1 trials Phase 2+
- Andrzej JakubowiakUniversity of Chicago Comprehensive Cancer Center · 1 of 1 trials Phase 2+
Registry trials of pomalidomide, iberdomide 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; 130 of 217 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. 8 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
68 trials of drugs against CUL4A were stopped early; 3 give no reason
Terminated, withdrawn and suspended interventional trials of pomalidomide, iberdomide, 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 68.
- suspended · 2026-10-19 · National Cancer Institute (NCI) · Iberdomide“Scheduled Interim Monitoring”
- suspended · 2026-10-02 · Alliance for Clinical Trials in Oncology · Iberdomide“Enrollment to Dose Level 1 cohort has been met”
- terminated · 2026-09-28 · Mayo Clinic · Pomalidomide“slow accrual”
- suspended · 2026-07-13 · Hackensack Meridian Health · Iberdomide“Temporary Hold Pending Amendment Approval”
- terminated · 2026-07-09 · Celgene · matched by the registry's drug synonyms“Business objectives have changed”
- terminated · 2026-01-29 · Teva Branded Pharmaceutical Products R&D LLC · Pomalidomide“Due to strategic reasons (no safety concerns).”
- withdrawn · 2026-01-14 · Teva Branded Pharmaceutical Products R&D LLC · Pomalidomide“Business Decision (no enrollment)”
- terminated · 2026-01-05 · Universitätsklinikum Hamburg-Eppendorf · pomalidomide/bortezomib/dexamethasone (PVD), daratumumab/pomalidomide/dexamethasone (DPD)“The reason for the end of recruitment is that the recruitment target could not be achieved despite all efforts and the G-BA (financing party) does not consider a continuation of the AlloRelapseMM study to be expedient.”
- terminated · 2025-10-21 · University of California, San Diego · Pomalidomide“The trial met its primary endpoint.”
- terminated · 2025-10-08 · Amgen · Pomalidomide“business decision, not safety reasons.”
- terminated · 2025-09-04 · M.D. Anderson Cancer Center · Pomalidomide“<75% participant accrual”
- terminated · 2025-05-02 · Gilead Sciences · Pomalidomide“This study was terminated early due to the Sponsor's decision to discontinue development of the investigational drug and close the program.”
- terminated · 2025-04-29 · Celgene · matched by the registry's drug synonyms“Business objectives have changed.”
- terminated · 2025-03-04 · Celgene · ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone“Change in business priorities.”
- terminated · 2025-02-25 · Hackensack Meridian Health · Pomalidomide“Low Accrual”
- terminated · 2025-02-20 · Fondazione IRCCS Policlinico San Matteo di Pavia · daratumumab and pomalidomide“low patient enrollment rate”
- terminated · 2025-02-19 · Intergroupe Francophone du Myelome · Ixazomib/Pomalidomide/Dexamethasone“Recruitment issue, 26 patients enrolled instead of 70 initially planned”
- terminated · 2025-02-14 · Multiple Myeloma Research Consortium · Elotuzumab, pomalidomide, dexamethasone“Pharmaceutical support has been discontinued.”
- terminated · 2025-01-08 · Zhejiang DTRM Biopharma · matched by the registry's drug synonyms“Despite the efforts of our dedicated team and initial progress, we were unable to secure the necessary financial resources to continue the study. We appreciate the support and participation of all involved.”
- terminated · 2024-12-24 · Seagen Inc. · pomalidomide“Study closed due to portfolio prioritization”
- terminated · 2024-10-26 · iTeos Therapeutics · Iberdomide“Company operational decision. Decision to stop study is not due to safety or efficacy concerns”
- withdrawn · 2024-07-16 · Dana-Farber Cancer Institute · Pomalidomide“Study support withdrawn”
- terminated · 2024-07-09 · Celgene · Pomalidomide“Lack of efficacy”
- withdrawn · 2024-05-31 · Celgene · Pomalidomide“Business objectives have changed”
- terminated · 2024-04-17 · Stemline Therapeutics, Inc. · matched by the registry's drug synonymsNo reason given
Paediatric incentives and obligations for CUL4A's drugs
For pomalidomide, iberdomide: 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 · CUL4A 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: yes · EMEA-002636-PIP01-19 (Iberdomide, Treatment of mature B-cell neoplasms): W: decision granting a waiver in all age groups for all conditions or indications, 3 Jan 2020; EMEA-001457-PIP01-13 (Pomalidomide, Treatment of post-essential thrombocythaemia myelofibrosis;Treatment of post-polycythaemia vera myelofibrosis): W: decision granting a waiver in all age groups for all conditions or indications, 2 Sept 2013Rule: 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/3/09/672 expired 8 Oct 2009: Treatment of multiple myeloma; EU/3/10/759 withdrawn 27 Jul 2010: Treatment of post-essential thrombocythaemia myelofibrosis; EU/3/10/758 withdrawn 27 Jul 2010: Treatment of post-polycythaemia vera myelofibrosis; EU/3/10/757 withdrawn 27 Jul 2010: Treatment of primary myelofibrosis; +1 moreRule: 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 · Pomalidomide Teva: authorised since 14 Nov 2024; Pomalidomide Krka: authorised since 24 Jul 2024; Pomalidomide Accord: authorised since 26 Jul 2024; Pomalidomide Zentiva: authorised since 24 Jul 2024; +2 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 pomalidomide, iberdomideRule: 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 · 4 interventional studies of pomalidomide, iberdomide include patients under 18; 2 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, 2026-11-12
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 4 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.