PIK3CG phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
ENSG00000105851 · protein coding · Open Targets profile
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). 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. Links G protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T- lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B- lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non- muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein- coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras- activation, to promote neutrophil functional responses (By similarity). {ECO:0000250|UniProtKB:Q9JHG7, ECO:0000269|PubMed:11277933, ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730, ECO:0000269|PubMed:16123124, ECO:0000269|PubMed:21393242, ECO:0000269|PubMed:31554793, ECO:0000269|PubMed:33054089, ECO:0000269|PubMed:7624799}.
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
- UniProt loc high conf, GO CC high conf, Human Protein Atlas loc
- PROTAC
- Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.5377100110054016 (upper bound 0.6731200218200684). 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 35 registry trials, updated in the last three years, of the most advanced drugs against PIK3CG (duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Nadene ZackCelcuity Inc · 2 of 2 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+
- Daniel MorgensternThe Hospital for Sick Children - Canadian Study Chair · 1 of 1 trials Phase 2+
- David ZieglerSydney Children's Hospital - Australian Study Chair · 1 of 1 trials Phase 2+
- Donald W ParsonsChildren's Oncology Group · 1 of 1 trials Phase 2+
- Ezra CohenUniversity of California, San Diego · 1 of 1 trials Phase 2+
- Howard FineWeill Medical College of Cornell University · 1 of 1 trials Phase 2+
- Ian E KropECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Jacques VargaftigInstitut Curie - Hôpital René Huguenin · 1 of 1 trials Phase 2+
- James GarnerKazia Therapeutics Limited · 1 of 1 trials Phase 2+
- Juanita LopezNational Health Service, United Kingdom · 1 of 1 trials Phase 2+
- Keith T FlahertyECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Luis N Gonzalez CastroDana-Farber Cancer Institute · 1 of 1 trials Phase 2+
- Panagiotis KonstantininopoulosDana-Farber Cancer Institute · 1 of 1 trials Phase 2+
Registry trials of duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisib 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; 23 of 35 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. Source: ClinicalTrials.gov, fetched live.
48 trials of drugs against PIK3CG were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisib, 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 48.
- 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.”
- 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 · 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.”
- withdrawn · 2023-04-27 · Roswell Park Cancer Institute · BuparlisibNo reason given
- terminated · 2022-08-22 · Vanderbilt-Ingram Cancer Center · Taselisib“Interim analysis - toxicity”
- withdrawn · 2022-07-28 · Rutgers, The State University of New Jersey · matched by the registry's drug synonyms“Research cancelled”
- terminated · 2022-07-12 · Hoffmann-La Roche · Taselisib“The Sponsor discontinued the manufacturing and development of taselisib due to modest clinical benefit and limited tolerability.”
- terminated · 2021-10-11 · Prince of Songkla University · matched by the registry's drug synonyms“Sponsor terminated to continue any clinical trials with study drug”
- terminated · 2021-02-10 · Restorbio Inc. · matched by the registry's drug synonyms“Insufficient accrual rate”
- terminated · 2021-01-13 · Won Kim · matched by the registry's drug synonyms“Lack of Accrual”
- terminated · 2020-12-19 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Decision by Sponsor to to terminate the study early.”
- terminated · 2020-12-08 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Study did not meet Phase Ib primary objective to establish the maximum tolerated dose/recommended dose for Phase II”
- withdrawn · 2020-04-28 · Abramson Cancer Center at Penn Medicine · Gedatolisib“due to business decision regarding the study drug.”
- withdrawn · 2019-11-22 · Restorbio Inc. · Dactolisib“Phase 3 trial RTB-101-204 study did not meet its primary endpoint”
- terminated · 2019-10-04 · University of Florida · Gedatolisib“Slow accrual”
- terminated · 2019-09-03 · Emory University · BuparlisibNo reason given
- terminated · 2019-04-10 · Cliniques universitaires Saint-Luc- Université Catholique de Louvain · matched by the registry's drug synonyms“Novartis decided to stop the marketing of BEZ235”
- terminated · 2019-02-05 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms“Due to slow accrual the supllier of BKM120 asked we cease further enrollment.”
- terminated · 2019-01-30 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Novartis decided not to pursue further development of buparlisib program (assessment of moderate PFS benefit with know, but manageable, buparlisib profile).”
- terminated · 2019-01-29 · Anne Chang · Buparlisib“Business Decision”
- terminated · 2019-01-08 · Pfizer · matched by the registry's drug synonyms“See termination reason in detailed description.”
- terminated · 2019-01-08 · Pfizer · matched by the registry's drug synonyms“Enrollment to the study was terminated on 11Nvo2014 due to slow recruitment. There were no safety or efficacy issues that contributed to this decision.”
- terminated · 2018-10-29 · Pfizer · matched by the registry's drug synonyms“Refer to Detailed Description for documentaion of Termination Statement.”
- terminated · 2018-10-11 · Novartis Pharmaceuticals · Buparlisib, Buparlisib placebo“Due to DLTs/AEs safety profile considered challenging.”
Paediatric incentives and obligations for PIK3CG's drugs
For duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisib: 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 · PIK3CG 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-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 2024Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-003607-PIP01-24, 2026-11-11
- EU orphan designation: no · No EU orphan designation names duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisibRule: 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 duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisibRule: 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 duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisibRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 9 interventional studies of duvelisib monohydrate, buparlisib, taselisib, gedatolisib, dactolisib, paxalisib, pictilisib, samotolisib, voxtalisib, pilaralisib, sonolisib, eganelisib include patients under 18; 5 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, 2026-11-12
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 30 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.