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Protein / target

Apoptosis regulator Bcl-2

Encoded byBCL2P10415Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

DNA-binding transcription factor binding

Strongest disease association

Diabetes Mellitus, Type 2

Via encoding gene BCL2 · Genetic evidence · score 0.77

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

Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.

View complete UniProt function annotation

Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondrial membrane permeability (PubMed:11368354). Appears to function in a feedback loop system with caspases (PubMed:11368354). Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1) (PubMed:11368354). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function (PubMed:18570871, PubMed:20889974, PubMed:21358617). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785)

Subcellular location

Mitochondrion outer membraneNucleus membraneEndoplasmic reticulum membraneCytoplasm
Domains and Gene Ontology detail (66)

Gene Ontology

  • CBcl-2 family protein complex
  • Ccytoplasm
  • Ccytosol
  • Cendoplasmic reticulum
  • Cendoplasmic reticulum membrane
  • Cmembrane
  • Cmitochondrial outer membrane
  • Cmitochondrion
  • Cmyelin sheath
  • Cnuclear membrane
  • Cnucleus
  • Cpore complex

239 aa · 26 kDa · 2 isoforms

Biological roles

Reactome v97

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

Cell proliferation & survivalGOImmune signallingGO · ReactomeApoptosis & cell deathUniProt · GOTranscriptional regulationGO · Reactome
View supporting evidence

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Immune signalling

  • ·B cell proliferation
  • ·B cell receptor signaling pathway
  • ·humoral immune response
  • ·positive regulation of B cell proliferation

Apoptosis & cell death

  • ·Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohemat…
  • ·apoptotic process
  • ·negative regulation of apoptotic process
  • ·negative regulation of neuron apoptotic process

Transcriptional regulation

  • ·DNA-binding transcription factor binding
  • ·Estrogen-dependent gene expression
View underlying pathways (8)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

BIKBECN1BNIP3BCL2L1NLRP1BECN2TP53PMAIP1NR4A1BCL2L11BCL2

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

1 medicine · 2 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
Broader indication categories (1)
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

3 medicines meet Open Targets' target-level approved-medicine definition; the 1 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.

navitoclax
Narrow target profileApprovedInhibitor

Apoptosis regulator Bcl-2 inhibitor

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

venetoclax
Narrow target profileApprovedInhibitor

Apoptosis regulator Bcl-2 inhibitor

Indicated for Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasms

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

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 BCL2

Gene-level evidence surfaced through the gene BCL2that 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
0.96Well supported

Genetic evidence dominant · Open Targets 0.74

Multiple Myeloma
0.89Well supported

Clinical evidence dominant · Open Targets 0.50

Neoplasms
0.84Well supported

Clinical evidence dominant · Open Targets 0.60

Prostate carcinoma
0.81Well supported

Genetic evidence dominant · Open Targets 0.50

Diabetes Mellitus, Type 2
0.80Well supported

Genetic evidence dominant · Open Targets 0.49

View evidence synthesis (5)
Leukemia, Lymphocytic, Chronic, B-CellWell supported
0.96
agreement 0.871.00
Genetic39%Clinical37%Somatic mutation15%Literature8%RNA expression0%

Open Targets aggregate 0.74 · 5 independent evidence families

Multiple MyelomaWell supported
0.89
agreement 0.810.97
Clinical27%Genetic25%Pathway17%Somatic mutation17%Animal model9%Literature5%

Open Targets aggregate 0.50 · 6 independent evidence families

NeoplasmsWell supported
0.84
agreement 0.750.93
Clinical46%Somatic mutation22%Genetic21%Literature11%

Open Targets aggregate 0.60 · 4 independent evidence families

Prostate carcinomaWell supported
0.81
agreement 0.700.92
Genetic62%Somatic mutation27%Literature12%

Open Targets aggregate 0.50 · 3 independent evidence families

Diabetes Mellitus, Type 2Well supported
0.80
agreement 0.660.93
Genetic87%Literature13%

Open Targets aggregate 0.49 · 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-Cell0.74
Neoplasms0.60
Lymphoma, Large B-Cell, Diffuse0.55
Neurodegenerative Diseases0.54
Leukemia, Myeloid, Acute0.51
Multiple Myeloma0.50
Prostate carcinoma0.50
Diabetes Mellitus, Type 20.49
Leukemia, Lymphoid0.49
Lymphoid neoplasm0.46

Drug development

7 compounds recorded · 3 approved · 4 in clinical development

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 (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (7)
OBLIMERSEN SODIUMPhase 3
NAVITOCLAXApproval
OBLIMERSENApproval
APG-2575Phase 3
OBATOCLAX MESYLATEPhase 3
OBATOCLAXPhase 2
VENETOCLAXApproval

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 (uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt SigP or TMHMMPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCastneurotoxicityClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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)

RECRUITING · via venetoclax · NCT07294677

ClinicalTrials.gov via the drug-target graph.

What's happening now

6

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. Trial status changed2026-07-31

    A Phase 2 Study of Venetoclax Monotherapy in Japanese Subjects With Relapsed or Refractory Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma

    Status changed to Active, not recruiting · ClinicalTrials.gov · via venetoclax

  2. Trial status changed2026-07-31

    Study of Cladribine+Venetoclax After Failure of Venetoclax+Hypomethylating Agent in Monocytic AML

    Status changed to Active, not recruiting · ClinicalTrials.gov · via venetoclax

  3. Trial status changed2026-07-28

    Daratumumab Combined With Venetoclax and Dexamethasone for Newly Diagnosed Light-Chain Amyloidosis Patients With Translocation (11;14): A Multicenter Phase 2 Study

    Status changed to Active, not recruiting · ClinicalTrials.gov · via venetoclax

  4. Trial status changed2026-07-14

    Phase 1b Study of Pembrolizumab, Decitabine +/- Venetoclax Combination Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

    Status changed to Suspended · ClinicalTrials.gov · via venetoclax

  5. Safety communication2021-12-10

    Drug Safety Update: Venetoclax (Venclyxto▼): updated recommendations on tumour lysis syndrome (TLS)

    mhra · safety · mhra · via venetoclax

  6. Regulatory approval2016-12-04

    Approval: Venclyxto (EMA)

    ema · regulatory · ema · via venetoclax

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.