TP53 tumor protein p53
ENSG00000141510 · protein coding · Open Targets profile
Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:35618207, PubMed:36634798, PubMed:38653238, PubMed:9840937). Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:38653238, PubMed:9840937). Negatively regulates cell division by controlling expression of a set of genes required for this process (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (PubMed:12524540, PubMed:17189187). Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492). {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:24652652, ECO:0000269|PubMed:35618207, ECO:0000269|PubMed:36634798, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:9840937}.
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
- Advanced Clinical, Structure with Ligand, High-Quality Ligand, Med-Quality Pocket, Druggable Family
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.2582100033760071 (upper bound 0.41835999488830566). 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 30 registry trials, updated in the last three years, of the most advanced drugs against TP53 (teprasiran, idasanutlin, navtemadlin, eprenetapopt, contusugene ladenovec, siremadlin, cenersen, alrizomadlin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Joachim GullboTheradex Oncology · 2 of 2 trials Phase 2+
- Asmita MishraH. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612 · 1 of 1 trials Phase 2+
- Charlie GourleyEdinburgh Cancer Research Centre, The University of Edinburgh · 1 of 1 trials Phase 2+
- David S SchrumpNational Cancer Institute (NCI) · 1 of 1 trials Phase 2+
- David SallmanMoffitt Cancer Center, Tampa, US · 1 of 1 trials Phase 2+
- Jean-Yves BLAYCentre Leon Berard · 1 of 1 trials Phase 2+
- Pierre Fenauxservice Hématologie Séniors Hôpital Saint Louis · 1 of 1 trials Phase 2+
- Shaji KumarMayo Clinic · 1 of 1 trials Phase 2+
- Kevin R KellyCity of Hope Comprehensive Cancer Center LAO · 0 of 2 trials Phase 2+
- Amar GajjarSt. Jude Children's Research Hospital · 0 of 1 trials Phase 2+
- Eudocia LeeNational Cancer Institute (NCI) · 0 of 1 trials Phase 2+
- Hans C LeeUniversity of Texas MD Anderson Cancer Center LAO · 0 of 1 trials Phase 2+
- Meng X WelliverNRG Oncology · 0 of 1 trials Phase 2+
Registry trials of teprasiran, idasanutlin, navtemadlin, eprenetapopt, contusugene ladenovec, siremadlin, cenersen, alrizomadlin 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; 17 of 28 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.
37 trials of drugs against TP53 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of teprasiran, idasanutlin, navtemadlin, eprenetapopt, contusugene ladenovec, siremadlin, cenersen, alrizomadlin, 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 37.
- withdrawn · 2026-03-17 · National Cancer Institute (NCI) · alrizomadlin“The study is being withdrawn due to the CRADA with the company not being finalized”
- terminated · 2026-02-10 · National Cancer Institute (NCI) · Navtemadlin“Inadequate accrual rate”
- terminated · 2025-11-13 · National Cancer Institute (NCI) · Navtemadlin“Drug supply issues”
- terminated · 2025-10-10 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Business decision”
- terminated · 2025-08-07 · Novartis Pharmaceuticals · Siremadlin“Sponsor Decision”
- terminated · 2025-05-16 · Novartis Pharmaceuticals · Siremadlin“Study has been stopped following the strategic decision from the Sponsor. Not based on any safety findings or safety concerns with siremadlin.”
- terminated · 2025-03-17 · Aprea Therapeutics · APR-246 (eprenetapopt) + Acalabrutinib in CLL, APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in CLL, APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RT, APR-246 (eprenetapopt) 4.5 g/d + Venetoclax + Rituximab in RT“Sponsor decision”
- terminated · 2024-12-20 · Hoffmann-La Roche · Idasanutlin“Study was terminated by the sponsor based on insufficient tolerability and efficacy to proceed beyond Part 1b.”
- withdrawn · 2024-03-27 · St. Jude Children's Research Hospital · Idasanutlin“Drug withdrawn by company.”
- terminated · 2024-03-22 · Kartos Therapeutics, Inc. · matched by the registry's drug synonyms“In September 2023, the study was terminated because of a Sponsor decision, unrelated to safety concerns.”
- withdrawn · 2024-03-22 · Kartos Therapeutics, Inc. · Navtemadlin, Navtemadlin Placebo“Sponsor Decision”
- terminated · 2023-11-07 · Hoffmann-La Roche · Idasanutlin“The Sponsor made the decision to terminate the study due to start up and recruitment issues caused by limited resource availability at the treating centers.”
- terminated · 2023-08-16 · Kartos Therapeutics, Inc. · matched by the registry's drug synonyms“Unanticipated and extremely high screen failure rate. There was no evidence of safety concerns in the study.”
- terminated · 2022-10-06 · Insel Gruppe AG, University Hospital Bern · matched by the registry's drug synonyms“Insufficient recruitment”
- terminated · 2022-09-29 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“The combination part of the study was terminated early due to business reasons”
- terminated · 2022-06-21 · Hoffmann-La Roche · Idasanutlin“Sponsor's decision to terminate the study after Phase 1; will not proceed with Phase 2.”
- withdrawn · 2022-03-10 · M.D. Anderson Cancer Center · Eprenetapopt“PI Request”
- terminated · 2022-01-11 · Hoffmann-La Roche · Idasanutlin“The study was stopped for futility based on efficacy results at the interim analysis; no unexpected safety findings were observed.”
- terminated · 2021-12-13 · Peter MacCallum Cancer Centre, Australia · matched by the registry's drug synonyms“Funding ceased”
- terminated · 2021-12-08 · Hoffmann-La Roche · Idasanutlin“The Sponsor decided to discontinue the development of idasanutlin in the polycythemia vera indication.”
- terminated · 2021-12-07 · Hoffmann-La Roche · Idasanutlin“Sponsor's decision to terminate the study after Phase 1; will not proceed with Phase 2.”
- terminated · 2021-08-11 · Vanderbilt-Ingram Cancer Center · Idasanutlin“Low accrual/Loss of funding”
- terminated · 2021-07-16 · Quark Pharmaceuticals · teprasiran“Study completed day 90 for primary endpoint but was terminated early for one year follow up due to results not meeting efficacy outcome at Day 90.”
- terminated · 2021-02-21 · Eleos, Inc. · cenersen“Company went out of business”
- terminated · 2020-06-02 · MultiVir, Inc. · matched by the registry's drug synonyms“Arm C rolled into parallel study; Arms A and B halted for greater efficacy in Arm C”
Paediatric incentives and obligations for TP53's drugs
For teprasiran, idasanutlin, navtemadlin, eprenetapopt, contusugene ladenovec, siremadlin, cenersen, alrizomadlin: 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: yes · TP53 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: 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-001489-PIP02-19 (Idasanutlin, Treatment of all conditions included in the category of malignant neoplasms (except nervous system, haematopoietic and lymphoid tissue)): PM: decision on the application for modification of an agreed PIP, 15 May 2020; EMEA-001489-PIP01-13-M02 (Idasanutlin, Treatment of acute lymphoblastic leukaemia;Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 18 Mar 2020Rule: 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/3/25/3178 positive 9 Jan 2026: Treatment of myelofibrosis; EU/3/21/2556 positive 14 Jan 2022: Treatment of Merkel cell carcinoma; EU/3/10/751 withdrawn 6 Jun 2010: Prevention of delayed graft function after renal transplantation; EU/3/08/587 positive 3 Dec 2008: Treatment of chronic lymphocytic leukaemiaRule: 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 teprasiran, idasanutlin, navtemadlin, eprenetapopt, contusugene ladenovec, siremadlin, cenersen, alrizomadlinRule: 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 teprasiran, idasanutlin, navtemadlin, eprenetapopt, contusugene ladenovec, siremadlin, cenersen, alrizomadlinRule: 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 · 2 interventional studies of teprasiran, idasanutlin, navtemadlin, eprenetapopt, contusugene ladenovec, siremadlin, cenersen, alrizomadlin 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, 2026-11-11
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 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.