PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
ENSG00000171608 · 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:9235916). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396). 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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity. {ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:20081091, ECO:0000269|PubMed:22020336, ECO:0000269|PubMed:9235916}.
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
- GO CC high conf
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.1627500057220459 (upper bound 0.23649999499320984). 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 131 registry trials, updated in the last three years, of the most advanced drugs against PIK3CD (leniolisib, duvelisib monohydrate, parsaclisib, umbralisib, copanlisib, idelalisib, buparlisib, taselisib, dactolisib, zandelisib, gedatolisib, paxalisib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Albert AssadIncyte Corporation · 3 of 3 trials Phase 2+Ph3NCT04551066 · To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)brief
- Fred ZhengIncyte Corporation · 3 of 3 trials Phase 2+
- Kathleen ButlerIncyte Corporation · 2 of 2 trials Phase 2+
- Nadene ZackCelcuity Inc · 2 of 2 trials Phase 2+
- Senthilkumar DamodaranECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Alexey V DanilovCity of Hope Medical Center · 1 of 2 trials Phase 2+
- Timothy A YapUniversity of Texas MD Anderson Cancer Center LAO · 1 of 2 trials Phase 2+
- Alexey DanilovCity of Hope Medical Cneter · 1 of 1 trials Phase 2+
- Anthony GONCALVESInstitut Paoli-Calmettes · 1 of 1 trials Phase 2+
- Anthony MatoUniversity of Pennsylvania Center for CLL · 1 of 1 trials Phase 2+
- Ashley MargolChildren's Hospital Los Angeles · 1 of 1 trials Phase 2+
- Benedito CarneiroBrown 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+
- Christian GrommesMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Christian SchmidtLMU Klinikum, Medical department III · 1 of 1 trials Phase 2+
Registry trials of leniolisib, duvelisib monohydrate, parsaclisib, umbralisib, copanlisib, idelalisib, buparlisib, taselisib, dactolisib, zandelisib, gedatolisib, paxalisib 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; 84 of 129 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.
141 trials of drugs against PIK3CD were stopped early; 27 give no reason
Terminated, withdrawn and suspended interventional trials of leniolisib, duvelisib monohydrate, parsaclisib, umbralisib, copanlisib, idelalisib, buparlisib, taselisib, dactolisib, zandelisib, gedatolisib, paxalisib, 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 141.
- terminated · 2026-04-21 · Institut Paoli-Calmettes · matched by the registry's drug synonyms“Drug development withdrawn”
- terminated · 2026-03-30 · Pharming Technologies B.V. · matched by the registry's drug synonyms“All participant have transitioned to commercial product or compassionate use.”
- terminated · 2026-02-27 · Massachusetts General Hospital · Umbralisib“Umbralisib development terminated; closed to accrual 8/29/2022”
- suspended · 2026-02-13 · Dana-Farber Cancer Institute · Gedatolisib“Funding and drug supply to continue the study are pending.”
- terminated · 2026-02-04 · Incyte Corporation · parsaclisib“A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this 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 · 2026-01-06 · H. Lee Moffitt Cancer Center and Research Institute · Umbralisib“Drug no longer available”
- terminated · 2025-12-02 · Henan Cancer Hospital · Parsaclisib“The clinical development of parsaclisib was stopped by it's manufacturer.”
- terminated · 2025-11-03 · Incyte Corporation · matched by the registry's drug synonyms“A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.”
- terminated · 2025-10-21 · Incyte Corporation · parsaclisib“The study was terminated due to futility.”
- terminated · 2025-10-02 · Incyte Corporation · parsaclisib“The study was terminated due to futility.”
- 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”
- terminated · 2025-06-17 · Gilead Sciences · Idelalisib“The goal of the study was to improve tolerability while maintaining or increasing efficacy. The results of this study showed no efficacy advantage although the combinations were well tolerated.”
- withdrawn · 2025-06-15 · VA Office of Research and Development · copanlisib“The study drug is not available.”
- 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 · 2025-03-04 · Columbia University · Copanlisib“Enrollment challenges”
- terminated · 2024-12-31 · MEI Pharma, Inc. · Zandelisib (ME-401)“discontinuation of zandelisib program”
- terminated · 2024-12-13 · TG Therapeutics, Inc. · matched by the registry's drug synonyms“Strategic/Business decision”
- terminated · 2024-12-11 · Bayer · Copanlisib (BAY80-6946)“Company decided to terminate this study due to study did not meet the primary endpoint.”
- terminated · 2024-11-21 · Fondazione Italiana Linfomi - ETS · Idelalisib“Study was halted prematurely due to safety, since tocity stopping rules have been met”
Paediatric incentives and obligations for PIK3CD's drugs
For leniolisib, duvelisib monohydrate, parsaclisib, umbralisib, copanlisib, idelalisib, buparlisib, taselisib, dactolisib, zandelisib, gedatolisib, paxalisib: 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 · PIK3CD 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 · EMA/PE/0000248263 (leniolisib phosphate, Treatment of activated phosphoinositide 3-kinase delta syndrome (APDS)): PM: decision on the application for modification of an agreed PIP, 10 Jul 2025; 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-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-002696-PIP03-22 (Parsaclisib (hydrochloride), Treatment of myelofibrosis): W: decision granting a waiver in all age groups for all conditions or indications, 8 Jul 2022; +5 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/3/25/3123 positive 22 Aug 2025: Treatment of common variable immunodeficiency (CVID); EU/3/20/2339 positive 19 Oct 2020: Treatment of activated phosphoinositide 3-kinase delta syndrome; EU/3/22/2659 positive 18 Jul 2022: Treatment of autoimmune haemolytic anaemia; +7 moreRule: 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 · Joenja: authorised since 21 May 2026, orphan medicine, exceptional circumstances; Zydelig: authorised since 18 Sept 2014; Aliqopa: application withdrawn, orphan medicine; Parsaclisib Incyte Biosciences Distribution B.V.: application withdrawnRule: 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 leniolisib, duvelisib monohydrate, parsaclisib, umbralisib, copanlisib, idelalisib, buparlisib, taselisib, dactolisib, zandelisib, gedatolisib, paxalisibRule: 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 · 19 interventional studies of leniolisib, duvelisib monohydrate, parsaclisib, umbralisib, copanlisib, idelalisib, buparlisib, taselisib, dactolisib, zandelisib, gedatolisib, paxalisib include patients under 18; 8 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 46 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.