RBX1 ring-box 1
ENSG00000100387 · protein coding · Open Targets profile
E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair (PubMed:10230407, PubMed:10579999, PubMed:11961546, PubMed:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:22748924, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:32355176, PubMed:33417871, PubMed:37844242, PubMed:38326650, PubMed:39504960, PubMed:39667934, PubMed:38316879). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (PubMed:27565346). The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex mediates ubiquitination of Pol II subunit POLR2A at 'Lys-1268', a critical TC- NER checkpoint (PubMed:32355176, PubMed:34526721). Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:35982156). Core component of a Cul9-RING ubiquitin ligase complex composed of CUL9 and RBX1, which mediates mono- ubiquitination of p53/TP53 (PubMed:38605244). Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A (PubMed:19920177). {ECO:0000269|PubMed:10230407, ECO:0000269|PubMed:10579999, ECO:0000269|PubMed:11027288, ECO:0000269|PubMed:11961546, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16751180, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19679664, ECO:0000269|PubMed:19920177, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:29769719, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:33417871, ECO:0000269|PubMed:34526721, ECO:0000269|PubMed:35982156, ECO:0000269|PubMed:37844242, ECO:0000269|PubMed:38316879, ECO:0000269|PubMed:38326650, ECO:0000269|PubMed:38605244, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934}.
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 Pocket
- PROTAC
- Database Ubiquitination, Half-life Data
gnomAD loss of function constraint: o/e – (upper bound –). 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 RBX1 (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 RBX1 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 RBX1'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 · RBX1 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), 2026-11-11
- 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, 2026-11-11
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 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.