PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
ENSG00000121879 · protein coding · Open Targets profile
Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:23936502, PubMed:28676499). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, PubMed:28676499). PIP3 plays a key role by recruiting PH domain- containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (PubMed:23936502, PubMed:28676499). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity). {ECO:0000250|UniProtKB:P42337, ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:23936502, ECO:0000269|PubMed:26593112, ECO:0000269|PubMed:28676499}.
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 Withdrawn means the drug was pulled from the market or from development.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 med conf
- PROTAC
- Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.1953900009393692 (upper bound 0.269459992647171). 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 170 registry trials, updated in the last three years, of the most advanced drugs against PIK3CA (copanlisib, inavolisib, alpelisib, dactolisib, taselisib, buparlisib, gedatolisib, paxalisib, pilaralisib, SF-1126, pictilisib, samotolisib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Senthilkumar DamodaranECOG-ACRIN Cancer Research Group · 3 of 3 trials Phase 2+
- Antonio LlombartArnau de Vilanova Hospital, Valencia (Spain) · 2 of 2 trials Phase 2+
- Nadene ZackCelcuity Inc · 2 of 2 trials Phase 2+
- Timothy A YapUniversity of Texas MD Anderson Cancer Center LAO · 1 of 2 trials Phase 2+
- Adam CohenInova Schar Cancer Institute · 1 of 1 trials Phase 2+
- Alexey DanilovCity of Hope Medical Cneter · 1 of 1 trials Phase 2+
- Alina MarkovaMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Andreas SchneeweissNational Center for Tumor Diseases (NCT) · 1 of 1 trials Phase 2+
- Anna PassarelliNational Cancer Institute, Naples · 1 of 1 trials Phase 2+
- Anthony GONCALVESInstitut Paoli-Calmettes · 1 of 1 trials Phase 2+
- Ashley MargolChildren's Hospital Los Angeles · 1 of 1 trials Phase 2+
- Åslaug HellandOslo University Hospital · 1 of 1 trials Phase 2+
- Benedito CarneiroBrown University · 1 of 1 trials Phase 2+
- Bryan P SchneiderIndiana University · 1 of 1 trials Phase 2+
- Chong-Xian PanVA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA · 1 of 1 trials Phase 2+
Registry trials of copanlisib, inavolisib, alpelisib, dactolisib, taselisib, buparlisib, gedatolisib, paxalisib, pilaralisib, SF-1126, pictilisib, samotolisib 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; 101 of 159 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. 11 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
104 trials of drugs against PIK3CA were stopped early; 12 give no reason
Terminated, withdrawn and suspended interventional trials of copanlisib, inavolisib, alpelisib, dactolisib, taselisib, buparlisib, gedatolisib, paxalisib, pilaralisib, SF-1126, pictilisib, samotolisib, 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 104.
- terminated · 2026-10-19 · Novartis Pharmaceuticals · Alpelisib“Sponsor Decision”
- terminated · 2026-10-15 · Spanish Breast Cancer Research Group · Alpelisib“Study prematurely terminated due to recruitment challenges, low incidence of the target population, evolving treatment landscape, ethical considerations, and inability to ensure funding through study completion.”
- terminated · 2026-10-14 · UNICANCER · Alpelisib“poor accrual”
- terminated · 2026-09-10 · Novartis Pharmaceuticals · alpelisib“The study was terminated following a strategic decision to halt recruitment due to persistently slow enrollment. This decision was not driven by any new or unexpected safety concerns.”
- terminated · 2026-07-10 · Novartis Pharmaceuticals · Alpelisib“Novartis terminated the trial early because the collected data were sufficient to perform the analysis stated for the primary endpoint.”
- terminated · 2026-07-07 · M.D. Anderson Cancer Center · Alpelisib“<75% participation”
- terminated · 2026-04-21 · Institut Paoli-Calmettes · matched by the registry's drug synonyms“Drug development withdrawn”
- suspended · 2026-02-13 · Dana-Farber Cancer Institute · Gedatolisib“Funding and drug supply to continue the study are pending.”
- withdrawn · 2026-02-09 · Hoffmann-La Roche · Inavolisib“Sponsor's decision”
- terminated · 2026-02-04 · Centre Hospitalier Universitaire Dijon · Taselisib (GDC0032)“In accordance with the protocol, following the occurrence of two SUSARs, the TOTEM trial was stopped early for safety reasons.”
- terminated · 2026-01-09 · M.D. Anderson Cancer Center · Copanlisib“Copanlisib development was discontinued by Bayer following withdrawal of copanlisib in relapsed follicular lymphoma in November 2023.”
- terminated · 2025-11-24 · Sanofi · Alpelisib“Sponsor decision to prematurely stop the study, not linked to any safety concern.”
- terminated · 2025-10-01 · National Cancer Institute (NCI) · Copanlisib“Inadequate accrual rate”
- terminated · 2025-09-08 · Institut Curie · matched by the registry's drug synonyms“No objective response was observed at the first step. The treatment was considered ineffective, with a complete clinical trial suspension.”
- terminated · 2025-08-08 · Fondazione Italiana Linfomi - ETS · Copanlisib“low enrollment rate”
- terminated · 2025-07-22 · Cancer Trials Ireland · Copanlisib“Accrual rate to date was too low to finish the trial in a reasonable timeframe”
- withdrawn · 2025-06-15 · VA Office of Research and Development · copanlisib“The study drug is not available.”
- terminated · 2025-05-31 · Bryan Schneider, MD · Inavolisib“Funder Decision”
- terminated · 2025-05-26 · Mayo Clinic · Copanlisib Hydrochloride“funding - sponsor filing Chapter 11 bankruptcy”
- withdrawn · 2025-05-22 · Inhye Ahn · Copanlisib“Bayer is no longer funding due to lack of accrual”
- terminated · 2025-04-10 · Inova Health Care Services · matched by the registry's drug synonyms“Lack of enrollment to meet the primary and secondary study goals”
- terminated · 2025-03-04 · Columbia University · Copanlisib“Enrollment challenges”
- terminated · 2024-12-11 · Bayer · Copanlisib (BAY80-6946)“Company decided to terminate this study due to study did not meet the primary endpoint.”
- withdrawn · 2024-10-31 · Memorial Sloan Kettering Cancer Center · Copanlisib“Study drug not available per sponsor”
- terminated · 2024-10-09 · Novartis Pharmaceuticals · Alpelisib“Study was early terminated due to slow recruitment and emerging data showing that prophylactic use of metformin may prevent or reduce the incidence of all-grades alpelisib-related hyperglycemia. The decision was not driven by safety concerns”
Paediatric incentives and obligations for PIK3CA's drugs
For copanlisib, inavolisib, alpelisib, dactolisib, taselisib, buparlisib, gedatolisib, paxalisib, pilaralisib, SF-1126, pictilisib, samotolisib: 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 · PIK3CA 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-003607-PIP01-24 (buparlisib, Treatment of head and neck epithelial malignant neoplasms): W: decision granting a waiver in all age groups for all conditions or indications, 14 Aug 2024; EMEA-002016-PIP05-23 (alpelisib, Treatment of lymphatic malformations associated with a PIK3CA mutation): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 12 Apr 2024; EMEA-001757-PIP02-15-M03 (Copanlisib, Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic and lymphoid tissue);Treatment of mature B-cell neoplasms): PM: decision on the application for modification of an agreed PIP, 9 Sept 2022; EMEA-002016-PIP03-19-M02 (alpelisib, Treatment of PIK3CA related overgrowth spectrum): PM: decision on the application for modification of an agreed PIP, 30 Sept 2022; +2 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/3/18/2064 withdrawn 24 Aug 2018: Treatment of marginal zone lymphoma; EU/3/21/2420 positive 26 Mar 2021: Treatment of PIK3CA related overgrowth spectrum; EU/3/23/2841 positive 13 Oct 2023: Treatment of lymphatic malformationsRule: 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: yes · Piqray: authorised since 27 Jul 2020; Vijoice: authorised since 15 Jul 2026, orphan medicine, conditional; Itovebi: authorised since 18 Jul 2025; Vijoice: application withdrawn, orphan medicine; +1 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 copanlisib, inavolisib, alpelisib, dactolisib, taselisib, buparlisib, gedatolisib, paxalisib, pilaralisib, sf-1126, pictilisib, samotolisibRule: 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 · 26 interventional studies of copanlisib, inavolisib, alpelisib, dactolisib, taselisib, buparlisib, gedatolisib, paxalisib, pilaralisib, sf-1126, pictilisib, samotolisib include patients under 18; 18 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 32 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.