TLR9 toll like receptor 9
ENSG00000239732 · protein coding · Open Targets profile
Key component of innate and adaptive immunity (PubMed:14716310). TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms (PubMed:14716310). TLR9 is a nucleotide- sensing TLR which is activated by unmethylated cytidine-phosphate- guanosine (CpG) dinucleotides (PubMed:14716310). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:11564765, PubMed:17932028, PubMed:40980882). Also acts via ADCY7, leading to cyclic di-AMP (c-di- AMP) synthesis and activation of the NLRP3 inflammasome (By similarity). Plays a role in defense against systemic mouse cytomegalovirus infection (By similarity). Controls lymphocyte response to Helicobacter infection (By similarity). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (PubMed:23857366). {ECO:0000250|UniProtKB:Q9EQU3, ECO:0000269|PubMed:11564765, ECO:0000269|PubMed:14716310, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:23857366}.
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- Antibody
- GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.7731500267982483 (upper bound 1.1345000267028809). 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 194 registry trials, updated in the last three years, of the most advanced drugs against TLR9 (hydroxychloroquine, lefitolimod, agatolimod, 1018 iss, tilsotolimod, cobitolimod, bazlitoran, EMD-1201081), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Angela DeMicheleUniversity of Pennsylvania · 2 of 2 trials Phase 2+
- Jing HePeking University People's Hospital · 2 of 2 trials Phase 2+
- Sabine HazanProgenaBiome · 2 of 2 trials Phase 2+
- Sukeshi Patel AroraCancer Therapy & Research Center University of Texas Health Science Center San Antonio · 2 of 2 trials Phase 2+
- Robert JanssenDynavax Technologies Corporation · 1 of 2 trials Phase 2+
- Ahmed M SayedAljazeera (Al Gazeera) hospital · 1 of 1 trials Phase 2+
- Alfredo Hernandez-RuizClinica Somer · 1 of 1 trials Phase 2+
- Amadou A. SallInstitut Pasteur de Dakar, Senegal · 1 of 1 trials Phase 2+
- Amy ClarkAbramson Cancer Center at Penn Medicine · 1 of 1 trials Phase 2+
- Anbin HuangUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology · 1 of 1 trials Phase 2+
- Anthony JoshuaSt Vincent's Hospital, Sydney · 1 of 1 trials Phase 2+
- Arsène MEKINIANInternal Medecine_Hospital Saint Antoine · 1 of 1 trials Phase 2+
- Ashutosh M. ShuklaNorth Florida/South Georgia Veterans Health System, Gainesville, FL · 1 of 1 trials Phase 2+
- Assoc. Prof. Levent ĞANAYUniversity of Health Sciences Istanbul Ümraniye Training and Research Hospital · 1 of 1 trials Phase 2+
- Austin DuffyMater Misericordiae University Hospital · 1 of 1 trials Phase 2+
Registry trials of hydroxychloroquine, lefitolimod, agatolimod, 1018 iss, tilsotolimod, cobitolimod, bazlitoran, EMD-1201081 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; 175 of 188 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. 6 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
166 trials of drugs against TLR9 were stopped early; 4 give no reason
Terminated, withdrawn and suspended interventional trials of hydroxychloroquine, lefitolimod, agatolimod, 1018 iss, tilsotolimod, cobitolimod, bazlitoran, EMD-1201081, 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 166.
- terminated · 2026-10-06 · ECOG-ACRIN Cancer Research Group · Hydroxychloroquine“Slow accrual”
- withdrawn · 2026-09-08 · Apsen Farmaceutica S.A. · Hydroxychloroquine Sulfate, Hydroxychloroquine Sulfate + Azythromycin“This study was canceled before enrollment due to a decision by the Sponsor”
- terminated · 2026-07-20 · National Institute of Allergy and Infectious Diseases (NIAID) · matched by the registry's drug synonyms“The study is being closed early due to insufficient participant enrollment across study sites.”
- terminated · 2026-06-12 · Northwestern University · Hydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab“The study was closed due to accrual.”
- withdrawn · 2026-05-19 · Nicholas Carlson · Hydroxychloroquine“No funding”
- terminated · 2026-05-14 · University of Utah · Hydroxychloroquine“Lack of Funding”
- terminated · 2026-04-29 · Guy's and St Thomas' NHS Foundation Trust · Hydroxychloroquine“Recruitment was terminated early by the funder due to study sites' inability to recruit sufficient number of participants.”
- terminated · 2026-04-14 · University Hospital, Rouen · Hydroxychloroquine“Difficulty in enrolling new patients”
- terminated · 2026-04-13 · Cancer Trials Ireland · Hydroxychloroquine“Study terminated due to futility”
- withdrawn · 2026-04-06 · Assistance Publique - Hôpitaux de Paris · matched by the registry's drug synonyms“The study was terminated following revisions to the diagnostic criteria defining the target pathology, which significantly impacted the study design”
- terminated · 2026-03-27 · Incannex Healthcare Ltd · Hydroxychloroquine“Recruitment challenges”
- terminated · 2026-02-06 · Queen's Medical Center · Hydroxychloroquine“RECOVERY Trial results - no efficacy”
- terminated · 2025-12-03 · Matthias Griese · Hydroxychloroquine sulfate“Lack of ressources after inspection and appropriate correcting actions to be taken”
- terminated · 2025-09-25 · BioMed Valley Discoveries, Inc · Hydroxychloroquine“Lack of Enrollment for Remaining Open Baskets”
- terminated · 2025-09-23 · Sanofi · Hydroxychloroquine SAR321068“Rate of enrollment too slow to allow completion in a reasonable timeframe”
- withdrawn · 2025-09-15 · London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's · Hydroxychloroquine“Study Withdrawn”
- terminated · 2025-06-12 · National Institute of Allergy and Infectious Diseases (NIAID) · Hydroxychloroquine“Enrollment was closed before reaching the target. In the 1st interim analysis after enrollment closure, the follow up \& treatment of active participants were stopped early due to evidence of futility.”
- withdrawn · 2025-05-16 · Memorial Sloan Kettering Cancer Center · Hydroxychloroquine“Emerging evidence does not support the use of HCQ for treatment or prevention of SARS -CoV2 infection. No pts have been enrolled.”
- terminated · 2025-03-10 · Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS · Hydroxychloroquine“Difficulties in recruiting subjects were observed soon after the study was initiated. This difficulty was attributed to the decreased incidence of infections which occurred in the period following the first lock down.”
- terminated · 2025-02-10 · ScandiBio Therapeutics AB · Hydroxychloroquine + Metabolic cofactor supplementation, Hydroxychloroquine + Sorbitol“Planned enrollment was not fulfilled.”
- withdrawn · 2025-01-07 · Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland · Hydroxychloroquine“Sufficient number of subjects would probably not reach”
- terminated · 2024-12-18 · Columbia University · Hydroxychloroquine“Toxicity and Lack of Efficacy”
- terminated · 2024-10-26 · University of Michigan · Hydroxychloroquine lower dose, Hydroxychloroquine higher dose“Unable to recruit additional participants after multiple extensions to planned enrollment period.”
- terminated · 2024-10-18 · Gustave Roussy, Cancer Campus, Grand Paris · Tilsotolimod“The part A of the trial has been completed according to the protocol. The part B has not been opened because of unfeasibility (experimental products not yet available).”
- terminated · 2024-10-15 · McGill University Health Centre/Research Institute of the McGill University Health Centre · Hydroxychloroquine“Request of Health Canada after publication of https://doi.org/10.7326/M20-4207”
Paediatric incentives and obligations for TLR9's drugs
For hydroxychloroquine, lefitolimod, agatolimod, 1018 iss, tilsotolimod, cobitolimod, bazlitoran, EMD-1201081: 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 · TLR9 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-002318-PIP03-19 (tilsotolimod, Treatment of malignant melanoma): W: decision granting a waiver in all age groups for all conditions or indications, 21 Jun 2019Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-002318-PIP03-19, 2026-11-11
- EU orphan designation: yes · EU/3/21/2415 positive 26 Mar 2021: Treatment of small cell lung cancer; EU/3/16/1820 positive 12 Jan 2017: Treatment of antiphospholipid syndrome; EU/3/17/1963 positive 8 Oct 2009: Treatment of LIPIN1 diseaseRule: 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 hydroxychloroquine, lefitolimod, agatolimod, 1018 iss, tilsotolimod, cobitolimod, bazlitoran, emd-1201081Rule: 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 hydroxychloroquine, lefitolimod, agatolimod, 1018 iss, tilsotolimod, cobitolimod, bazlitoran, emd-1201081Rule: 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 · 57 interventional studies of hydroxychloroquine, lefitolimod, agatolimod, 1018 iss, tilsotolimod, cobitolimod, bazlitoran, emd-1201081 include patients under 18; 12 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.