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Protein / target

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform

Encoded byPIK3CDO00329Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
10
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

1-phosphatidylinositol-4,5-bisphosphate 3-kinase

Strongest disease association

Leukemia, Lymphocytic, Chronic, B-Cell

Via encoding gene PIK3CD · Clinical evidence · score 0.61

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

View complete UniProt function annotation

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

Subcellular location

Cytoplasm
Domains and Gene Ontology detail (51)

Domains & features

PI3K-ABDPI3K-RBDC2 PI3K-typePIK helicalPI3K/PI4K catalytic

Gene Ontology

  • Ccytoplasm
  • Ccytosol
  • Cphosphatidylinositol 3-kinase complex
  • Cphosphatidylinositol 3-kinase complex, class IA
  • Cplasma membrane
  • F1-phosphatidylinositol-3-kinase activity
  • F1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
  • F1-phosphatidylinositol-4-phosphate 3-kinase activity
  • FATP binding
  • Padaptive immune response
  • PB cell activation
  • PB cell chemotaxis

1044 aa · 119 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationUniProt · GOSynaptic signallingUniProtKinase signallingUniProt · GOImmune signallingUniProt · GO
View supporting evidence

Cell migration

  • ·Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosph…
  • ·B cell chemotaxis
  • ·cell migration
  • ·mast cell chemotaxis

Synaptic signalling

  • ·Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosph…

Kinase signalling

  • ·Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosph…
  • ·1-phosphatidylinositol-3-kinase activity
  • ·1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
  • ·1-phosphatidylinositol-4-phosphate 3-kinase activity

Immune signalling

  • ·Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosph…
  • ·adaptive immune response
  • ·B cell activation
  • ·B cell chemotaxis

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

2 medicines · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Leukemia, Lymphocytic, Chronic, B-Cell1 medicine
Lymphoma, Non-Hodgkin's1 medicine
Neoplasms2 medicines

10 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

idelalisib
Narrow target profileApprovedInhibitor

PI3-kinase p110-delta subunit inhibitor

Indicated for Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin's, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

copanlisib
Narrow target profileApprovedInhibitor

PI3-kinase p110-delta subunit inhibitor

Indicated for Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PIK3CD

Gene-level evidence surfaced through the gene PIK3CDthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Leukemia, Lymphocytic, Chronic, B-Cell
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Neoplasms
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.58

Lymphoma, Follicular
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.59

Lymphoma, Non-Hodgkin's
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Marginal zone lymphoma
0.64Moderately supported

Clinical evidence dominant · Open Targets 0.52

View evidence synthesis (5)
Leukemia, Lymphocytic, Chronic, B-CellWell supported
0.76
agreement 0.600.91
Clinical86%Literature14%

Open Targets aggregate 0.61 · 2 independent evidence families

NeoplasmsModerately supported
0.73
agreement 0.570.88
Clinical83%Literature17%

Open Targets aggregate 0.58 · 2 independent evidence families

Lymphoma, FollicularModerately supported
0.72
agreement 0.570.88
Clinical98%Literature2%

Open Targets aggregate 0.59 · 2 independent evidence families

Lymphoma, Non-Hodgkin'sModerately supported
0.69
agreement 0.540.85
Clinical94%Literature6%

Open Targets aggregate 0.56 · 2 independent evidence families

Marginal zone lymphomaModerately supported
0.64
agreement 0.490.80
Clinical99%Literature1%

Open Targets aggregate 0.52 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Leukemia, Lymphocytic, Chronic, B-Cell0.61
Lymphoma, Follicular0.59
Neoplasms0.58
Lymphoma, Non-Hodgkin's0.56
Marginal zone lymphoma0.52

Drug development

46 compounds recorded · 10 approved · 35 in clinical development · 1 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
LENIOLISIB PHOSPHATEApproval
PF-04691502Phase 2
DUVELISIB MONOHYDRATEApproval
VOXTALISIBPhase 2
PARSACLISIBApproval
BUPARLISIBPhase 3
SONOLISIBPhase 2
TASELISIBPhase 3
BGT-226Phase 1 2
PILARALISIBPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via copanlisib · NCT03474744

ACTIVE_NOT_RECRUITING · via copanlisib · NCT02465060

TERMINATED · via idelalisib · NCT02536300

ClinicalTrials.gov via the drug-target graph.

What's happening now

5

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2020-12-01
    Phase 1b study to investigate the safety and tolerability of idelalisib in Japanese patients with relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia.

    Japanese journal of clinical oncology · 2020 · 7 citations · Europe PMC · via idelalisib

  2. Safety communication2016-09-15

    Drug Safety Update: Idelalisib (Zydelig▼): updated indications and advice on minimising the risk of infection

    mhra · safety · mhra · via idelalisib

  3. Safety communication2016-05-10

    Drug Safety Update: Idelalisib (Zydelig▼): interim measures following signal of serious infection and deaths related to infection found in clinical trials

    mhra · safety · mhra · via idelalisib

  4. Regulatory approval2014-09-18

    Approval: Zydelig (EMA)

    ema · regulatory · ema · via idelalisib

  5. New publication2014-01-22
    PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma.

    The New England journal of medicine · 2014 · 813 citations · Europe PMC · via idelalisib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Related family literature

1

Papers about “Class Ia Phosphatidylinositol 3-Kinase” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity.

Tsay A · International journal of molecular sciences · 2023

via Class Ia Phosphatidylinositol 3-Kinase

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.