TNF tumor necrosis factor
ENSG00000232810 · protein coding · Open Targets profile
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T- cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity). {ECO:0000250|UniProtKB:P06804, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:22517918, ECO:0000269|PubMed:23396208}.
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 Withdrawn means the drug was pulled from the market or from development.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
- Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- Approved Drug, UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.32113999128341675 (upper bound 0.6032000184059143). 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 161 registry trials, updated in the last three years, of the most advanced drugs against TNF (afelimomab, ozoralizumab, infliximab, certolizumab pegol, golimumab, onercept, lenercept, nerelimomab, placulumab, remtolumab, ABBV-3373, pegsunercept), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- UCB Cares001 844 599 2273 (UCB) · 3 of 5 trials Phase 2+
- Kazuoki KondoMitsubihsi Tanabe Pharma Corporation · 3 of 3 trials Phase 2+
- Toshifumi HibiDepartment of Internal Medicine, Keio University School of Medicine · 3 of 3 trials Phase 2+
- Ying HuangChildren's Hospital of Fudan University · 3 of 3 trials Phase 2+
- Dirk ElewautUZ Ghent · 2 of 2 trials Phase 2+
- Fleur COHEN AUBARTInternal Medicine Department 2 - Hôpital Pitié-Salpêtrière · 2 of 2 trials Phase 2+
- Lissy de RidderErasmus Medical Center - Sophia Children's Hospital · 2 of 2 trials Phase 2+
- Marc FerranteIG/MAAG-DARM-LEVER, UZ Leuven, campus Gasthuisberg, Herestraat 49 3000 Leuven · 2 of 2 trials Phase 2+
- Phillip MinarChildren's Hospital Medical Center, Cincinnati · 2 of 2 trials Phase 2+
- Byong Duk YeAsan Medical Center · 1 of 2 trials Phase 2+
- Hira TariqServices Institute of Medical Sciences, Pakistan · 1 of 2 trials Phase 2+
- Marie-Claude RobertCentre hospitalier de l'Université de Montréal (CHUM) · 1 of 2 trials Phase 2+
- Yinghong WangM.D. Anderson Cancer Center · 1 of 2 trials Phase 2+
- Adriana TremouletUniversity of California, San Diego · 1 of 1 trials Phase 2+
- Ahmed A Abdel-KaderCairo University · 1 of 1 trials Phase 2+
Registry trials of afelimomab, ozoralizumab, infliximab, certolizumab pegol, golimumab, onercept, lenercept, nerelimomab, placulumab, remtolumab, ABBV-3373, pegsunercept 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; 119 of 154 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. 7 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
92 trials of drugs against TNF were stopped early; 7 give no reason
Terminated, withdrawn and suspended interventional trials of afelimomab, ozoralizumab, infliximab, certolizumab pegol, golimumab, onercept, lenercept, nerelimomab, placulumab, remtolumab, ABBV-3373, pegsunercept, 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 92.
- terminated · 2026-10-19 · University of Washington · Golimumab“The trial was ended sooner than expected due to a combination of factors, including slow accrual, lower than anticipated benefit to patients, and loss of funding from the study sponsor.”
- terminated · 2026-09-29 · ECOG-ACRIN Cancer Research Group · Infliximab“Slow accrual”
- terminated · 2026-06-22 · University Hospital, Montpellier · matched by the registry's drug synonyms“difficulty of inclusion”
- terminated · 2026-05-06 · Mats Remberger · matched by the registry's drug synonyms“Too slow recruitment”
- suspended · 2026-05-04 · Robert Flavell, MD, PhD · matched by the registry's drug synonyms“Lapse in study funding.”
- terminated · 2026-03-11 · Children's Hospital Medical Center, Cincinnati · Infliximab precision dosing“This was the Pilot study. The larger, confirmatory study has started”
- withdrawn · 2025-12-26 · Therakos LLC · Infliximab“Study Withdrawn by Sponsor prior to Enrollment.”
- terminated · 2025-11-20 · Assistance Publique Hopitaux De Marseille · matched by the registry's drug synonyms“new treatment on the market in direct competition with the new treatment proposed by the study. Recruitment difficulties.”
- withdrawn · 2025-10-06 · Abu Dhabi Stem Cells Center · matched by the registry's drug synonyms“Decision of the local healthcare authority”
- terminated · 2025-06-17 · Cambridge University Hospitals NHS Foundation Trust · Infliximab“NIHR withdrawal of funding”
- terminated · 2025-04-29 · Janssen Research & Development, LLC · Golimumab 50 mg“Neither dose achieved the study's primary or major secondary endpoints. The safety profile was consistent with previous ustekinumab studies.”
- terminated · 2025-04-29 · Janssen Research & Development, LLC · Golimumab 50 mg“This study was stopped because ustekinumab did not achieve key endpoints in a related study. The safety profile was consistent with past ustekinumab studies.”
- terminated · 2025-02-21 · Boston Medical Center · matched by the registry's drug synonyms“Unable to recruit adequate numbers of participants to answer the research question.”
- terminated · 2025-02-06 · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Infliximab“Slow recruitment”
- terminated · 2025-02-04 · Janssen Scientific Affairs, LLC · Infliximab“Study was terminated due to the inability to enroll a sufficient number of the required subject population”
- terminated · 2023-10-27 · Emory University · Infliximab“The study was suspended in March 2020 due to the COVID-19 pandemic and ultimately was terminated as it is not safe to test a potent anti-inflammatory drug with ongoing surges of COVID-19.”
- terminated · 2023-04-07 · Wenjie Zheng · Golimumab (GOL)“only one patient enrolled”
- terminated · 2022-09-19 · Mario Negri Institute for Pharmacological Research · Infliximab, Golimumab, Certolizumab Pegol“Slow recrutiment”
- withdrawn · 2022-08-09 · Children's Hospital of Fudan University · Infliximab“no funding”
- withdrawn · 2022-07-20 · Hospices Civils de Lyon · Infliximab“recruiting difficulties”
- terminated · 2021-12-28 · Pfizer · matched by the registry's drug synonyms“The Sponsor changed R\&D strategy and priority.”
- withdrawn · 2021-12-02 · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Golimumab“Withdrawn due to COVID-19 related clinical limitations”
- terminated · 2021-10-01 · Schneider Children's Medical Center, Israel · Infliximab“Difficulty to recruit patients and as high dose infliximab for severe UC is now the rule rather than the exception”
- withdrawn · 2021-06-23 · UCB Biopharma SRL · Certolizumab pegol“Sponsor decision”
- withdrawn · 2021-03-12 · Children's Hospital of Fudan University · Infliximab“lack of funding”
Paediatric incentives and obligations for TNF's drugs
For afelimomab, ozoralizumab, infliximab, certolizumab pegol, golimumab, onercept, lenercept, nerelimomab, placulumab, remtolumab, ABBV-3373, pegsunercept: 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 · TNF 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-000265-PIP02-11-M04 (golimumab, Treatment of ulcerative colitis): PM: decision on the application for modification of an agreed PIP, 28 Oct 2022; compliance positive 13 Dec 2024; EMEA-001071-PIP03-14-M01 (certolizumab pegol, Treatment of psoriasis): W: decision granting a waiver in all age groups for all conditions or indications, 7 Dec 2018; EMEA-001071-PIP02-12-M02 (certolizumab pegol, Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis)): W: decision granting a waiver in all age groups for all conditions or indications, 3 Jul 2017; EMEA-000265-PIP01-08-M04 (golimumab, Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, psoriatic arthritis, spondylarthritis and juvenile idiopathic arthritis)): PM: decision on the application for modification of an agreed PIP, 5 Sept 2014; compliance positive 10 Oct 2014; +1 moreRule: 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/3/26/3236 positive 20 May 2026: Treatment of Kawasaki 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 EU/3/26/3236, 2026-11-11
- Authorised in the EU: yes · Remicade: authorised since 13 Aug 1999; Gobivaz: authorised since 17 Nov 2025; Inflectra: withdrawn since 10 Sept 2013; Gotenfia: authorised since 10 Feb 2026; +8 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 afelimomab, ozoralizumab, infliximab, certolizumab pegol, golimumab, onercept, lenercept, nerelimomab, placulumab, remtolumab, abbv-3373, pegsunerceptRule: 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 · 111 interventional studies of afelimomab, ozoralizumab, infliximab, certolizumab pegol, golimumab, onercept, lenercept, nerelimomab, placulumab, remtolumab, abbv-3373, pegsunercept include patients under 18; 19 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 14 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.