RARA retinoic acid receptor alpha
ENSG00000131759 · protein coding · Open Targets profile
Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:21152046, PubMed:28167758, PubMed:37478846). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, PubMed:28167758). 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:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:19850744, PubMed:20215566, PubMed:37478846, PubMed:9267036). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758). {ECO:0000250|UniProtKB:P11416, ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:19398580, ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:21152046, ECO:0000269|PubMed:28167758, 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
- Antibody
- GO CC high conf
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.11680000275373459 (upper bound 0.2455900013446808). 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 183 registry trials, updated in the last three years, of the most advanced drugs against RARA (tretinoin, isotretinoin, adapalene, acitretin, tazarotene, tamibarotene, IRX4310, NRX195183), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Xiaohui ZhangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology · 3 of 3 trials Phase 2+Ph2NCT07586813 · Romiplostim N01 Plus ATRA for Persistent Isolated Chemotherapy-Induced Thrombocytopenia After Complete Remission of Gastrointestinal Solid Tumorsbrief
- Sara M FedericoChildren's Oncology Group · 2 of 2 trials Phase 2+
- Adam J EsbenshadeChildren's Oncology Group · 1 of 1 trials Phase 2+
- Ali AmarCombined Military Hospital Abbottabad · 1 of 1 trials Phase 2+
- Alice L YuChildren's Oncology Group · 1 of 1 trials Phase 2+
- Aliza HamadaniLahore Medical and Dental College · 1 of 1 trials Phase 2+
- Amara safdar SafdarAllied Hospital, Faisalabad Medical University · 1 of 1 trials Phase 2+
- Ami V DesaiChildren's Oncology Group · 1 of 1 trials Phase 2+
- Arnauld VERSCHUURCHU La Timone · 1 of 1 trials Phase 2+
- Arucha TreesirichodSrinakharinwirot University · 1 of 1 trials Phase 2+
- Ayesha Asad ChatthaGhurki Trust Teaching Hospital · 1 of 1 trials Phase 2+
- Benjamin N UngarIcahn School of Medicine at Mount Sinai · 1 of 1 trials Phase 2+
- Brian H. KushnerMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Carmen FaridProfessor of Dermatology · 1 of 1 trials Phase 2+
- Chris DeibertUniversity of Nebraska · 1 of 1 trials Phase 2+
Registry trials of tretinoin, isotretinoin, adapalene, acitretin, tazarotene, tamibarotene, IRX4310, NRX195183 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; 141 of 170 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. 13 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
80 trials of drugs against RARA were stopped early; 4 give no reason
Terminated, withdrawn and suspended interventional trials of tretinoin, isotretinoin, adapalene, acitretin, tazarotene, tamibarotene, IRX4310, NRX195183, 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 25 most recent of 80.
- terminated · 2026-10-08 · St. Marianna University School of Medicine · Tamibarotene“Lack of efficacy”
- withdrawn · 2026-07-07 · Peking Union Medical College Hospital · matched by the registry's drug synonyms“The study has not actually been conducted.”
- withdrawn · 2026-07-07 · Peking Union Medical College Hospital · matched by the registry's drug synonyms“The study has not actually been conducted.”
- terminated · 2025-12-18 · Mario Negri Institute for Pharmacological Research · matched by the registry's drug synonyms“Low enrolment rate”
- terminated · 2025-11-04 · Incyte Corporation · matched by the registry's drug synonyms“Strategic Business Decision”
- terminated · 2025-11-04 · Icahn School of Medicine at Mount Sinai · matched by the registry's drug synonyms“Interim analysis did not show any significant differences between groups”
- terminated · 2025-04-10 · Syros Pharmaceuticals · Tamibarotene“As per Sponsor decision, the study was terminated.”
- terminated · 2025-02-25 · Hackensack Meridian Health · matched by the registry's drug synonyms“Low Accrual”
- terminated · 2025-02-24 · Syros Pharmaceuticals · Tamibarotene“As per sponsor decision, the study was terminated.”
- terminated · 2024-12-09 · Taiho Oncology, Inc. · matched by the registry's drug synonyms“The study was terminated due to the changing treatment landscape, difficulty in enrolling eligible participants, and little likelihood of providing meaningful clinical benefit for the participants.”
- terminated · 2024-08-22 · M.D. Anderson Cancer Center · Isotretinoin“No Sponsor funding for continuation of trial”
- withdrawn · 2024-08-07 · University of Alabama at Birmingham · matched by the registry's drug synonyms“COVID-19 pandemic, unable to enroll participants”
- terminated · 2024-05-08 · University Hospital Regensburg · matched by the registry's drug synonyms“Due to financial reasons.”
- withdrawn · 2024-03-07 · M.D. Anderson Cancer Center · Tamibarotene“Zero participants accrued”
- withdrawn · 2024-03-06 · University of Oklahoma · Adapalene Gel“The original PI left the institution prior to final IRB approval and the remaining study team did not have the resources to continue.”
- terminated · 2024-03-04 · OHSU Knight Cancer Institute · Tretinoin“Low accrual”
- terminated · 2024-02-07 · Dana-Farber Cancer Institute · Topical Tazarotene“Difficulty with patient recruitment”
- withdrawn · 2023-06-07 · Massachusetts General Hospital · Isotretinoin“PI (Responsible Party) transferred to new institution prior to enrollment and protocol was closed.”
- withdrawn · 2023-04-13 · University of Louisville · Topical Adapalene Gel 0.1%“Study never received IRB approval.”
- withdrawn · 2023-04-06 · Massachusetts General Hospital · matched by the registry's drug synonyms“Study was planned prior to COVID-19; after pandemic teledermatology use became prevalent making the results of this study no longer necessary/relevant”
- terminated · 2022-11-04 · University of Cologne · matched by the registry's drug synonyms“Antibody supply was discontinued by United Therapeutics Corporation.”
- suspended · 2022-11-03 · Azidus Brasil · arbutin, tretinoin, triamcinoloneNo reason given
- withdrawn · 2022-09-01 · Y-mAbs Therapeutics · Isotretinoin“Study terminated due to business priorities”
- terminated · 2022-08-23 · Galderma R&D · Fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%“Enrollment closed”
- terminated · 2022-08-01 · Clementia Pharmaceuticals Inc. · matched by the registry's drug synonyms“Trial was terminated early to analyze the accumulated data and evaluate the efficacy, safety and future of palovarotene in MO.”
Paediatric incentives and obligations for RARA's drugs
For tretinoin, isotretinoin, adapalene, acitretin, tazarotene, tamibarotene, IRX4310, NRX195183, 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 · RARA 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-003263-PIP01-22 (clindamycin phosphate;benzoyl peroxide;adapalene, Treatment of acne vulgaris): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 14 Jul 2023; EMEA-000510-PIP02-10-M02 (tazarotene, Treatment of lamellar ichthyosis): PM: decision on the application for modification of an agreed PIP, 24 Oct 2012; EMEA-000892-PIP01-10 (clindamycin phosphate;tretinoin, Treatment of acne vulgaris): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 27 Aug 2010; compliance positive 10 Dec 2010Rule: 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/3/22/2701 withdrawn 11 Oct 2022: Treatment of autosomal recessive congenital ichthyosis; EU/3/23/2760 withdrawn 15 Feb 2023: Treatment of recessive X-linked ichthyosis; EU/3/22/2688 positive 10 Aug 2022: Treatment of myelodysplastic syndromes; EU/3/18/2053 positive 31 Jul 2018: Treatment of acute myeloid leukaemia; +2 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: no · EMA lists no centrally authorised medicine of tretinoin, isotretinoin, adapalene, acitretin, tazarotene, tamibarotene, irx4310, nrx195183, mofaroteneRule: 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: yes · Tretinoin [Vesanoid], 22 Nov 1995: Induction of remission in adults and pediatric patients 1 year of age and older with acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RARα gene expression, and who are refractory to or who have relapsed from anthracycline chemotherapy or for whom anthracycline-based chemotherapy is contraindicatedRule: 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 · 285 interventional studies of tretinoin, isotretinoin, adapalene, acitretin, tazarotene, tamibarotene, irx4310, nrx195183, mofarotene include patients under 18; 35 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 11 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.