SIGMAR1 sigma non-opioid intracellular receptor 1
ENSG00000147955 · protein coding · Open Targets profile
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112 (By similarity). {ECO:0000250|UniProtKB:O55242, ECO:0000269|PubMed:16472803, ECO:0000269|PubMed:9341151}.
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- Antibody
- UniProt loc high conf, UniProt SigP or TMHMM, GO CC med conf
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7084800004959106 (upper bound 1.0506000518798828). 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 66 registry trials, updated in the last three years, of the most advanced drugs against SIGMAR1 (pentazocine, dextromethorphan polistirex, carbetapentane, dextromethorphan), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Christine N. SangTranslational Pain Research, Brigham and Women's Hospital (Disclosure: Patent) · 2 of 2 trials Phase 2+
- Gisèle PICKERINGUniversity Hospital, Clermont-Ferrand · 1 of 2 trials Phase 2+
- Andreas DiaconTASK Applied Science Clinical Research Centre · 1 of 1 trials Phase 2+
- BioXcel MMBioXcel Therapeutics · 1 of 1 trials Phase 2+
- Chin-Bin YehTri-Service General Hospital (TSGH) · 1 of 1 trials Phase 2+
- DARLINTON-PETER CHIBUZOR C UGOJIAlex Ekwueme Federal University Teaching Hospital · 1 of 1 trials Phase 2+
- DEBASISH HOTAAIIMS Bhubaneswar · 1 of 1 trials Phase 2+
- Erin L Furr StimmingThe University of Texas Health Science Center, Houston · 1 of 1 trials Phase 2+
- Frederick G MoellerVirginia Commonwealth University · 1 of 1 trials Phase 2+
- Joshua C BrownMclean Hospital · 1 of 1 trials Phase 2+
- Mary F HebertUniversity of Washington · 1 of 1 trials Phase 2+
- Peter J van RoesselStanford University · 1 of 1 trials Phase 2+
- Rituparna MaitiAIIMS, Bhubaneswar · 1 of 1 trials Phase 2+
- Sahajal DhooriaPostgraduate Institute of Medical Education and Research, Chandigarh, India · 1 of 1 trials Phase 2+
- Takeshi MorimotoHyogo Medical University · 1 of 1 trials Phase 2+
Registry trials of pentazocine, dextromethorphan polistirex, carbetapentane, dextromethorphan 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; 53 of 64 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. 2 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
22 trials of drugs against SIGMAR1 were stopped early
Terminated, withdrawn and suspended interventional trials of pentazocine, dextromethorphan polistirex, carbetapentane, dextromethorphan, 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 22 most recent of 22.
- withdrawn · 2026-08-21 · Institute for Clinical Effectiveness, Japan · matched by the registry's drug synonyms“Before the enrolment of participants, the principal investigator was fired, and the study site did not allow the continuation of the study.”
- terminated · 2026-06-25 · Axsome Therapeutics, Inc. · AXS-05 (dextromethorphan-bupropion)“Study AXS-05-AD-305 was terminated due to completion of overall program objectives.”
- terminated · 2026-05-13 · Otsuka Pharmaceutical Development & Commercialization, Inc. · matched by the registry's drug synonyms“The study was terminated prematurely because of difficulty with recruiting.”
- terminated · 2026-01-28 · Axsome Therapeutics, Inc. · AXS-05 (dextromethorphan-bupropion)“This study was terminated once overall program objectives were met.”
- terminated · 2025-10-15 · Otsuka Pharmaceutical Development & Commercialization, Inc. · matched by the registry's drug synonyms“The AVP-786 program was discontinued, the recruitment was stopped and all participants are no longer being examined or receiving intervention.”
- terminated · 2025-08-21 · Janssen Research & Development, LLC · Dextromethorphan 30 mg“The study was stopped as all post-marketing commitments had been fulfilled or released”
- terminated · 2022-10-10 · University Hospital, Clermont-Ferrand · Dextromethorphan“Recruitment difficulties”
- terminated · 2022-03-02 · Genprex, Inc. · matched by the registry's drug synonyms“Trial terminated by sponsor after decision to evaluate combination of quaratusugene ozeplasmid and osimertinib instead of further evaluating quaratusugene ozeplasmid and erlotinib.”
- terminated · 2021-09-16 · University of Colorado, Denver · matched by the registry's drug synonyms“Study was terminated due to the change in funding.”
- terminated · 2021-05-24 · Emalex Biosciences Inc. · matched by the registry's drug synonyms“A number of subjects withdrew consent leaving the study without adequate power to achieve its primary end points.”
- terminated · 2021-04-28 · Pfizer · Dextromethorphan Hydrobromide“The study was prematurely discontinued due to slow enrollment during the 2019/2020 cold season. No safety or efficacy concerns led to the decision to terminate”
- withdrawn · 2020-10-27 · Takeda · Dextromethorphan“No enrollment”
- terminated · 2019-10-29 · St. Joseph's Hospital and Medical Center, Phoenix · matched by the registry's drug synonyms“Sponsor decided to stop study early”
- terminated · 2019-05-14 · University of Southern California · Dextromethorphan“The surgeon changed pain control protocol for all patients. Continued enrollment impossible under approved protocol.”
- terminated · 2017-07-03 · Avanir Pharmaceuticals · matched by the registry's drug synonyms“The study was terminated prematurely because of difficulty with recruiting.”
- withdrawn · 2016-08-25 · Duke University · matched by the registry's drug synonyms“lack of funding”
- withdrawn · 2015-10-06 · Emergency NGO Onlus · matched by the registry's drug synonyms“The Study could not be started due to an insufficient number of new EVD cases.”
- withdrawn · 2014-12-23 · Children's National Research Institute · Dextromethorphan“lack of funding”
- terminated · 2014-04-23 · Hugo W. Moser Research Institute at Kennedy Krieger, Inc. · Dextromethorphan“Study changed to a placebo controlled trial of dextromethorphan”
- terminated · 2012-09-20 · Pfizer · Dextromethorphan“See termination reason in detailed description.”
- terminated · 2011-05-17 · University of Medicine and Dentistry of New Jersey · dextromethorphan hydrobromide“slow accrual”
- terminated · 2009-12-11 · University of Medicine and Dentistry of New Jersey · Dextromethorphan“slow accrual”
Paediatric incentives and obligations for SIGMAR1's drugs
For pentazocine, dextromethorphan polistirex, carbetapentane, dextromethorphan: 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 · SIGMAR1 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-001148-PIP01-11 (Dextromethorphan (hydrobromide);quinidine sulfate, Treatment of pseudobulbar affect (uncontrollable laughing and/or crying)): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 30 Sept 2011Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-001148-PIP01-11, 2026-11-11
- EU orphan designation: no · No EU orphan designation names pentazocine, dextromethorphan polistirex, carbetapentane, dextromethorphanRule: 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 · Nuedexta: withdrawn since 24 Jun 2013Rule: 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 Nuedexta, 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 pentazocine, dextromethorphan polistirex, carbetapentane, dextromethorphanRule: 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 · 30 interventional studies of pentazocine, dextromethorphan polistirex, carbetapentane, dextromethorphan 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, 2026-11-12
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 9 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.