RXRA retinoid X receptor alpha
ENSG00000186350 · protein coding · Open Targets profile
Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:11162439, PubMed:11915042, PubMed:37478846). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:16107141, PubMed:17761950, PubMed:18800767, PubMed:19167885, PubMed:28167758, PubMed:37478846). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:37478846, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632). {ECO:0000269|PubMed:10195690, ECO:0000269|PubMed:10874028, ECO:0000269|PubMed:11162439, ECO:0000269|PubMed:11915042, ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:1310260, ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:16107141, ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:18800767, ECO:0000269|PubMed:19167885, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:25417649, ECO:0000269|PubMed:26463675, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:29021580, ECO:0000269|PubMed:30216632, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9267036}.
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 Ligand, High-Quality Pocket, Druggable Family
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.11236000061035156 (upper bound 0.23623999953269958). 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 9 registry trials, updated in the last three years, of the most advanced drugs against RXRA (bexarotene, acitretin, IRX-4204, SDX-101), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Charlotte D JacobsStanford University · 1 of 1 trials Phase 2+
- Rui YinDepartment of Dermatology, Southwest Hospital, Third Military Medical University (Army Medical University) · 1 of 1 trials Phase 2+
- Brandon ImberMemorial Sloan Kettering Cancer Center · 0 of 1 trials Phase 2+
- Elaine LimNational Cancer Centre, Singapore · 0 of 1 trials Phase 2+
- Kevin CooperCase Comprehensive Cancer Center · 0 of 1 trials Phase 2+
- Martin E SandersIo Therapeutics, Inc. · 0 of 1 trials Phase 2+
Registry trials of bexarotene, acitretin, IRX-4204, SDX-101 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; 9 of 9 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.
21 trials of drugs against RXRA were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of bexarotene, acitretin, IRX-4204, SDX-101, mofarotene, 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 21 most recent of 21.
- suspended · 2026-03-03 · Io Therapeutics · matched by the registry's drug synonyms“Sponsor request for study hold”
- withdrawn · 2025-06-12 · Case Comprehensive Cancer Center · Bexarotene 1% Top Gel“Study closed prior to enrollment of first participant”
- terminated · 2025-05-14 · Io Therapeutics · matched by the registry's drug synonyms“Study drug supply expired. No replacement manufactured. Sponsor did not want to continue study.”
- terminated · 2021-03-10 · Icahn School of Medicine at Mount Sinai · Acitretin“Lack of subjects”
- terminated · 2020-12-17 · Abramson Cancer Center at Penn Medicine · Bexarotene“Study terminated. Eisai's Targretin acquired by another pharmaceutical company.”
- withdrawn · 2020-03-04 · Ottawa Hospital Research Institute · Acitretin“The study was withdrawn.”
- terminated · 2019-06-26 · University of Utah · Acitretin 25Mg Oral Capsule“lack of efficacy and lack of funding”
- terminated · 2019-03-06 · Dartmouth-Hitchcock Medical Center · Bexarotene (targretin)“other trials show no survival benefit of bexarotene with platinum-based chemo”
- terminated · 2018-12-26 · University of Arizona · Acitretin“Pharmaceutical company pulled support for the trial.”
- terminated · 2018-10-18 · University of Washington · matched by the registry's drug synonyms“Terminated due to slow accrual”
- withdrawn · 2018-07-19 · Günther Hofbauer · Chemopreventive application (Acitretin)“lack of subjects”
- terminated · 2018-07-09 · European Organisation for Research and Treatment of Cancer - EORTC · bexarotene“poor accrual”
- terminated · 2017-02-14 · Georgetown University · CS-7017 and Bexarotene“Drug no longer available”
- withdrawn · 2015-04-21 · Stiefel, a GSK Company · Acitretin (also called U0279)“Business decision. No patients were enrolled”
- terminated · 2015-04-21 · Merck Sharp & Dohme LLC · Comparator: bexarotene“The study was stopped due to low enrollment.”
- terminated · 2014-05-12 · Cephalon · SDX-101 (R-Etodolac)No reason given
- terminated · 2013-04-16 · Fox Chase Cancer Center · Bexarotene 1% gel“The response rate (5/8) had reached a statistical significant endpoint.”
- withdrawn · 2013-01-16 · University of Pittsburgh · Acitretin“Unable to enroll subjects by sponsor deadline”
- terminated · 2012-07-26 · Emergent Product Development Seattle LLC · matched by the registry's drug synonyms“New sponsor, other treatments available”
- terminated · 2012-06-11 · Cephalon · matched by the registry's drug synonymsNo reason given
- withdrawn · 2010-06-29 · Beersheva Mental Health Center · Bexarotene“The study withdrawn due to lack financial support”
Paediatric incentives and obligations for RXRA's drugs
For bexarotene, acitretin, IRX-4204, SDX-101, mofarotene: 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 · RXRA 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 bexarotene, acitretin, irx-4204, sdx-101, mofaroteneRule: 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: no · No EU orphan designation names bexarotene, acitretin, irx-4204, sdx-101, mofaroteneRule: 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 · Targretin: authorised since 29 Mar 2001Rule: 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 EPAR Targretin, 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 bexarotene, acitretin, irx-4204, sdx-101, mofaroteneRule: 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 bexarotene, acitretin, irx-4204, sdx-101, mofarotene include patients under 18; 0 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 8 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.