BCL-W (BCL2L2)
BCL-W is a pro-survival member of the BCL-2 protein family that restrains the intrinsic apoptosis-pathway by sequestering pro-apoptotic BH3-only proteins (BIM, BID, BAD, PUMA) via its hydrophobic binding groove. In aging biology, BCL-W is a critical component of the senescent cell anti-apoptotic programme (SCAP) in human lung fibroblasts — dual knockdown of BCL-W and BCL-xL is sufficient to trigger apoptosis in senescent IMR-90 cells, explaining why navitoclax (which inhibits BCL-2, BCL-xL, and BCL-W) is senolytic in this lineage while venetoclax (BCL-2-selective) is not 12. BCL-W has been somewhat overlooked relative to bcl-2 and bcl-xl in the senolytic literature but is now recognized as a non-redundant survival node in fibroblast-lineage senescent cells.
Naming note: The gene is BCL2L2 (BCL-2-like 2, HGNC:993); the encoded protein is variously called BCL-W or Bcl-w in the literature. This page uses BCL-W throughout. No pathway page named bcl-w exists; pathway context is covered under apoptosis-pathway and bcl-2-family-signaling.
Identity
| Field | Value |
|---|---|
| UniProt | Q92843 (B2CL2_HUMAN) |
| NCBI Gene | 599 |
| HGNC | 993 |
| Ensembl | ENSG00000129473 |
| HGNC symbol | BCL2L2 |
| Length | 193 amino acids (human; single canonical isoform per UniProt Q92843) |
| MW | ~20.7 kDa |
| Mouse ortholog | Bcl2l2 (highly conserved; one-to-one ortholog) |
| GenAge entry | not listed (BCL2L2 not in GenAge-human as of 2026-05-04) needs-canonical-id |
Domain organization
BCL-W contains the canonical four BH-domain architecture of anti-apoptotic BCL-2 family members plus a C-terminal transmembrane anchor [UniProt Q92843]:
| Domain | Residues (human) | Function |
|---|---|---|
| BH4 | ~9–29 | N-terminal; characteristic of anti-apoptotic members; required for full anti-apoptotic activity |
| BH3 | ~84–100 | Embedded within the folded structure; not available for trans-binding in the anti-apoptotic orientation; role in homo/heterodimerization |
| BH1 | ~85–104 | Forms the floor of the hydrophobic binding groove; together with BH2 constitutes the BH3-peptide receptor surface |
| BH2 | ~136–151 | Completes the hydrophobic groove; required for BAX/BAK and BH3-only protein sequestration |
| Transmembrane anchor | ~172–189 | Tail-anchored; targets BCL-W to the mitochondrial outer membrane (MOM); required for in vivo anti-apoptotic activity |
Note: Exact domain boundary residues above are from UniProt Q92843 annotations (accessed 2026-05-04). The Hinds 2003 NMR solution structure paper (EMBO J; DOI 10.1093/emboj/cdg144) reports that BCL-W’s C-terminal residues fold back into the hydrophobic BH3-binding groove, occluding it and restricting BH3-peptide access — a form of autoinhibition not observed in the truncated Bcl-xL structures available at the time. This is distinct from the BH4-groove interaction described for some other family members; the Hinds paper specifically shows the α9 helix (C-terminal tail) lies in the groove. Binding of a BH3 peptide displaces this tail, and displacement appears linked to tight membrane association. BCL-xL shows a similar C-terminal groove-occlusion in full-length protein. The in vivo functional significance (whether this represents a gating mechanism for BH3-only protein binding) is debated. needs-replication — the BCL-W C-terminal autoinhibition model is based on NMR solution structure analysis; whether this constitutes a kinetically relevant gate in living cells is unclear. — NOTE: The DOI 10.1093/emboj/cdg186 previously cited here maps to an unrelated Ikaros paper. Correct DOI is 10.1093/emboj/cdg144.
Discovery and mouse knockout phenotype
BCL-W was cloned in 1996 by Gibson et al. as a BCL-2 homolog with broad tissue expression 3. Initial characterization suggested it was broadly anti-apoptotic, consistent with other family members.
The Bcl2l2-null (BCL-W knockout) mouse, generated by Print et al. (1998), produced a striking and selective phenotype 4:
- Male-sterile: Bcl2l2-/- males are viable but infertile. Spermatogenic defect localizes to early-stage germ cells (spermatocytes); Sertoli cell survival also impaired. BCL-W appears to be a critical survival factor for postmitotic Sertoli cells.
- Female-fertile: Bcl2l2-/- females are fertile; no female reproductive phenotype.
- Otherwise grossly normal: Unlike Bcl-2-/- mice (which develop polycystic kidneys and lymphoid depletion) or Bcl-x-/- mice (embryonic lethal due to neural and erythroid apoptosis), BCL-W-null animals are healthy and reach normal lifespan.
This restricted phenotype positioned BCL-W as a specialized anti-apoptotic factor — critical in the male germline but broadly redundant elsewhere. The subsequent discovery of BCL-W’s role in fibroblast SCAP (see below) substantially revised this narrow view.
| Model | Lifespan | Primary phenotype |
|---|---|---|
| Bcl-2-/- | Normal-ish (early death from autoimmune kidney disease/lymphopenia) | Polycystic kidneys, lymphopenia, hypopigmentation |
| Bcl-x-/- (heterozygous) | Normal | KO is embryonic lethal; heterozygote no overt phenotype |
| Bcl2l2-/- | Normal | Male-sterile; spermatogenic defect; otherwise viable |
needs-human-replication — Human BCL2L2 loss-of-function variants in male infertility have not been extensively characterized. The mouse KO is not directly translatable. unsourced — no large human genomic study linking BCL2L2 variants to male infertility was found during curation.
BH3-only protein binding selectivity
Chen et al. (2005) systematically measured competitive binding affinities (IC50) of BH3 peptides to all five anti-apoptotic BCL-2 family members using a surface plasmon resonance (Biacore biosensor) competition assay 5. BCL-W affinities:
| BH3-only protein | BCL-W IC50 (nM) | BCL-2 IC50 (nM) | BCL-xL IC50 (nM) | Classification |
|---|---|---|---|---|
| bim | 4.3 | 2.6 | 4.6 | Very high affinity — binds all three comparably |
| puma | 5.1 | 3.3 | 6.3 | Very high affinity |
| BMF | 9.8 | 3.0 | 9.7 | High affinity |
| bad | 30 | 16 | 5.3 | Moderate affinity for BCL-W; high for BCL-xL |
| HRK | 49 | 320 | 3.7 | Moderate for BCL-W; low for BCL-2; high for BCL-xL |
| bid (BID BH3) | 40 | 6,800 | 82 | Moderate for BCL-W; low for BCL-2 |
| noxa | >100,000 (>100 μM) | >100,000 | >100,000 | Negligible — selective non-binder of BCL-2/xL/w layer |
All IC50 values from Chen et al. 2005 Figure 3A (representative experiment; variation <2-fold across experiments per figure legend) 5.
Key selectivity point: BCL-W shares the broad-spectrum binding pattern of BCL-2 and BCL-xL — binding BIM, PUMA, BMF, BAD, HRK, and BID with varying affinities but not NOXA. NOXA selectively antagonizes MCL-1 and A1 (IC50 24 nM and 180 nM, respectively, per the same table). This defines two functionally distinct anti-apoptotic layers: BCL-2/BCL-xL/BCL-W (broad-spectrum) vs. MCL-1/A1 (NOXA-sensitive, narrow-spectrum).
Correction note: Earlier extractions of this table reported BAD ~5 nM, BID ~5 nM, and BMF ~5 nM for BCL-W. The Chen 2005 Figure 3A data shows BCL-W IC50s of BAD = 30 nM, BID = 40 nM, BMF = 9.8 nM. The ~5 nM values correspond to BCL-2 or BCL-xL affinities for those ligands, not BCL-W.
The same study confirmed that BCL-W and BCL-xL have broadly similar binding profiles, with BCL-W and BCL-2 being most closely related in overall pattern (Figure 3B) 5.
Mechanism of apoptosis inhibition
BCL-W operates by the same two-mode mechanism as other anti-apoptotic BCL-2 family members at the mitochondrial outer membrane:
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Direct BAX/BAK sequestration — BCL-W binds the activated/membrane-integrated forms of BAX and BAK, preventing their oligomerization and pore formation. BCL-W is “loosely associated” with mitochondrial membranes in healthy cells and becomes tightly membrane-bound during apoptotic stimulation (UniProt Q92843).
-
BH3-only protein sequestration — BCL-W binds activator BH3-only proteins (BIM, BID) before they engage BAX/BAK, and sensitizer BH3-only proteins (BAD, PUMA, BMF) before they displace activators from anti-apoptotic guards.
BH3-mimetic mechanism: Drugs like navitoclax present a synthetic BH3 helix to the BCL-W groove, competitively displacing sequestered BH3-only proteins → released BIM/BID activate BAX/BAK → MOMP → cytochrome c → caspase cascade → apoptosis. Venetoclax’s BCL-2-selective structure does not effectively engage the BCL-W groove, explaining its inability to senolytically clear BCL-W-dependent cells.
BCL-W in senescence and aging
Senescent cell anti-apoptotic programme (SCAP) — IMR-90 fibroblasts
The most aging-relevant discovery for BCL-W came from two complementary siRNA/pharmacological studies of the SCAP in human lung fibroblasts (IMR-90):
Yosef et al. 2016 (Nature Communications) — multiple senescence inducers in IMR-90 1:
- Used siRNA knockdown of individual BCL-2 family members to dissect which members are required for senescent IMR-90 survival. The primary siRNA knockdown experiment was performed in DIS (DNA damage-induced senescence by etoposide) cells. OIS (oncogene-induced, H-RasV12) and RS (replicative senescence) cells were also tested with ABT-737 and pharmacological inhibitors but the BCL-W + BCL-xL dual siRNA experiment specifically used DIS cells.
- BCL-W + BCL-xL dual knockdown caused ~53% reduction in senescent DIS IMR-90 cell viability (each alone causing only minor reductions). BCL-2 siRNA had only a minor additive effect when combined with BCL-xL — the paper notes siRNA against BCL-2 only modestly reduced its protein level despite mRNA knockdown.
- ABT-737 (which inhibits BCL-2, BCL-W, and BCL-xL) phenocopied the dual knockdown across all three senescence induction types (DIS, RS, OIS), confirming pharmacological tractability.
- ABT-199 (venetoclax, BCL-2-selective) alone was insufficient to senolytically clear DIS or MEF senescent cells — consistent with BCL-W + BCL-xL being the dominant survival nodes. ABT-199 did reduce OIS IMR-90 viability in a dose-dependent manner (Fig. 2b), which the authors attribute to lower BCL-2 levels in OIS cells and/or the oncogenic context increasing BCL-2 dependence.
- In vivo, ABT-737 eliminated DNA-damage-induced senescent cells from mouse lungs (irradiation model, n=5/group) and p53-induced senescent epidermal cells (K5-rtTA/tet-p14ARF transgenic skin model) in young mice (3-week-old); in vivo experiments used targeted senescence induction in young animals, not chronologically aged mice.
Zhu et al. 2016 (Aging Cell) — radiation-induced senescence in IMR-90 (10 Gy) 2:
- Used radiation (10 Gy) as the senescence inducer and a different siRNA combination protocol than Yosef 2016.
- Found that the triple BCL-2 + BCL-xL + BCL-w combination was required for IMR-90 senolysis. BCL-xL alone or BCL-2 + BCL-xL together were insufficient.
- This study’s triple-combination finding vs Yosef 2016’s dual BCL-W + BCL-xL finding reflect different induction conditions and possibly the relative contribution of BCL-2 under different senescent states. contradictory-evidence — both findings are considered real; the discrepancy in BCL-2’s sufficiency contribution likely reflects inducer-specific variation in SCAP composition.
SCAP dependency by cell type (summary):
| Cell type | Primary SCAP node(s) | BCL-W required? | Source |
|---|---|---|---|
| IMR-90 (lung fibroblasts; DIS — etoposide; ABT-737 also active in RS and OIS) | BCL-W + BCL-xL (dual siRNA sufficient; each alone insufficient; BCL-2 minor additive) | Yes — essential | Yosef 2016 1 |
| IMR-90 (lung fibroblasts; radiation-induced, 10 Gy) | BCL-2 + BCL-xL + BCL-W (triple siRNA) | Yes — co-required | Zhu 2016 2 |
| HUVECs (endothelial) | BCL-xL dominant (BCL-xL siRNA alone senolytic) | Minor/additive | Zhu 2016 2 |
| Primary preadipocytes | EFNB1, EFNB3, PI3KCD, p21, PAI-2 (not BCL-2 family) | No | Zhu 2015 6 |
BCL-W’s role in fibroblast SCAP explains a key therapeutic observation: navitoclax (BCL-2 + BCL-xL + BCL-W) is senolytic in IMR-90-type fibroblast populations, as is venetoclax (BCL-2 only) in OIS-IMR-90 but not DIS/MEF senescent cells, and A-1331852 (BCL-xL-selective) is also senolytic in IMR-90 cells per Zhu 2017 despite BCL-xL siRNA alone being insufficient per Zhu 2016 (see contradictory-evidence in pharmacology section).
| Dimension | Status | Notes |
|---|---|---|
| Pathway conserved in humans? | yes | BCL-W sequence and SCAP function confirmed in human IMR-90 cells (human primary line) |
| Phenotype conserved in humans? | partial | Demonstrated in human cell lines; primary aged human fibroblasts in vivo uncharacterized |
| Replicated in humans? | no | No human clinical trial of BCL-W-targeted senolysis; navitoclax trials ongoing for cancer not aging |
needs-human-replication — All BCL-W SCAP data is from human cell lines (in vitro); direct evidence in primary aged human tissue is lacking.
Pharmacology
Navitoclax (ABT-263) — pan-BCL-2/BCL-xL/BCL-W inhibitor
Navitoclax is the primary pharmacological tool for interrogating BCL-W’s contribution to SCAP. It inhibits BCL-2, BCL-xL, and BCL-W with Ki values each ≤1 nM (per Tse et al. 2008 — see navitoclax for full binding data; Yosef 2016 does not report Ki values), making it effectively a pan-inhibitor of the BCL-2/BCL-xL/BCL-W layer.
- Senolytic mechanism in IMR-90: BCL-W and BCL-xL are displaced from their BH3-only cargoes → BIM/BAD freed → BAX/BAK activation → MOMP → apoptosis.
- Dose-limiting toxicity: BCL-xL inhibition in platelets causes thrombocytopenia (see bcl-xl). This toxicity is not BCL-W-specific — it is an on-target BCL-xL effect. BCL-W appears not to have a critical platelet-survival role analogous to BCL-xL.
- Senolytic activity in vivo: ABT-737 (an earlier-generation close analog of navitoclax) eliminated senescent cells from mouse lungs and skin in targeted senescence models (young mice) 1. Navitoclax senolytic activity in chronologically aged mice was demonstrated in Chang et al. 2016 (10.1038/nm.4010 — PDF not locally downloaded; claims not verified) 7.
See navitoclax for full compound data (implicit stub; needs seeding).
Venetoclax (ABT-199) — BCL-2-selective; does NOT inhibit BCL-W
Venetoclax was specifically engineered to spare BCL-xL (and therefore platelets). Its binding surface does not effectively engage BCL-W’s hydrophobic groove either. This selectivity explains its failure as a senolytic in fibroblast-lineage senescent cells: with BCL-W + BCL-xL intact, the SCAP remains functional despite BCL-2 inhibition 12.
See venetoclax (implicit stub; may overlap with bcl-2 pharmacology section) and bcl-2 for the full BCL-2-selective senolytic discussion.
A-1331852 — BCL-xL-selective; senolytic in HUVECs and IMR-90, not preadipocytes
A-1331852 is highly BCL-xL-selective. In Zhu et al. 2017, A-1331852 was senolytic in both HUVECs and IMR-90 cells (Figs 2b–i: significant reduction in ATP, cell survival, and caspase 3/7 induction in senescent but not proliferating cells) but was NOT senolytic in primary human preadipocytes 8. This finding is consistent with BCL-xL being individually rate-limiting for HUVEC and IMR-90 senescent cell survival, and also consistent with the Zhu 2016 triple-knockdown finding if BCL-xL is the dominant node. The relationship between A1331852’s IMR-90 activity and the Zhu 2016 finding that BCL-xL siRNA alone is insufficient for IMR-90 senolysis represents a dose/selectivity discrepancy that is not fully resolved — the pharmacological inhibitor may achieve effective enough BCL-xL occupancy to overcome the redundancy seen at siRNA-level knockdown. contradictory-evidence — A1331852 (BCL-xL-selective drug) is senolytic in IMR-90 per Zhu 2017, yet BCL-xL siRNA alone was insufficient per Zhu 2016; may reflect incomplete siRNA knockdown vs. pharmacological inhibition kinetics.
BCL-W in cancer
BCL-W is elevated in some lymphomas and solid tumors, though it is less prominent in oncology literature than BCL-2 or BCL-xL. Navitoclax’s clinical development in cancer inherently targets BCL-W (among other family members). No selective BCL-W inhibitor is in clinical development. BCL-W’s cancer biology is not comprehensively reviewed on this wiki; this page focuses on the senolytic-relevant aging context.
Pathway membership
- apoptosis-pathway — BCL-W is a core node in intrinsic apoptosis regulation; sequesters BAX/BAK and BH3-only proteins at the MOM checkpoint upstream of MOMP.
- bcl-2-family-signaling — BCL-W is a member of the BCL-2 protein family; part of the pro-survival sub-family (BCL-2, BCL-xL, BCL-W, MCL-1, A1/BCL2A1).
- cellular-senescence — BCL-W is a SCAP component in fibroblast-lineage senescent cells; its upregulation contributes to the apoptosis resistance of senescent IMR-90 cells.
Key interactors
| Interactor | Interaction type | Functional consequence |
|---|---|---|
| bax | Direct binding (groove:BH3 of activated BAX) | BCL-W sequesters BAX, preventing oligomerization at MOM |
| bak | Direct binding | Sequesters BAK at MOM; prevents pore formation |
| bim | BH3:groove (IC50 4.3 nM) | Activator BH3-only; BCL-W sequestration prevents BIM from engaging BAX/BAK |
| bad | BH3:groove (IC50 30 nM) | Sensitizer; BAD phosphorylation by Akt dissociates from BCL-W |
| bid | BH3:groove (IC50 40 nM) | tBID (activator); sequestered by BCL-W with moderate affinity |
| puma | BH3:groove (IC50 5.1 nM) | Sensitizer/activator; high-affinity BCL-W ligand |
| noxa | Negligible (IC50 >100 μM) | Does NOT bind BCL-W — NOXA selectively targets MCL-1/A1 |
| bmf | BH3:groove (IC50 9.8 nM) | Sensitizer; sequestered by BCL-W |
| bcl-xl | Functional redundancy in SCAP | BCL-W and BCL-xL together constitute the dominant SCAP in IMR-90 fibroblasts |
Limitations and open questions
| Gap | Tag | Notes |
|---|---|---|
| BCL-W SCAP contribution discrepancy (dual vs triple) between Yosef 2016 and Zhu 2016 | contradictory-evidence | Yosef 2016 (DIS/etoposide): BCL-W + BCL-xL dual siRNA sufficient; Zhu 2016 (radiation/10 Gy): triple BCL-2 + BCL-xL + BCL-W required. Additional discrepancy: A1331852 (BCL-xL drug) is senolytic in IMR-90 (Zhu 2017) despite BCL-xL siRNA alone being insufficient (Zhu 2016). Inducer-dependent and siRNA-vs-drug SCAP response differences not fully explained |
| In vivo senolysis in chronologically aged mice | needs-replication | Yosef 2016 in vivo data used targeted senescence induction in young mice; Chang 2016 navitoclax-aged-mouse data not locally verified |
| BCL-W SCAP role in primary human aged fibroblasts | needs-human-replication | All data from human cell lines (IMR-90); primary aged human tissue characterization absent |
| BCL-W contribution to platelet survival | unsourced | BCL-W is reportedly dispensable for platelet survival (unlike BCL-xL); no primary source establishing this claim was located during this curation pass |
| Human BCL2L2 germline variants and male infertility | needs-replication | Mouse KO shows male-sterile phenotype; human genetic data linking BCL2L2 loss-of-function to infertility is sparse |
| GenAge entry | needs-canonical-id | BCL2L2 does not appear in GenAge-human; aging relevance derives from SCAP biology rather than direct lifespan manipulation |
| BCL-W C-terminal autoinhibition model | needs-replication | Hinds 2003 NMR solution structure (DOI 10.1093/emboj/cdg144; previously mis-cited as cdg186) describes the C-terminal α9 helix occluding the hydrophobic binding groove; BH3 peptide binding displaces the C-terminus, linked to tight membrane association; in vivo functional significance as a kinetic gate remains debated and not independently confirmed |
| Selective BCL-W inhibitor development | long-term-unknown | No selective BCL-W chemical probe or clinical compound exists; all pharmacological BCL-W data derives from pan-inhibitors (navitoclax/ABT-737) |
Footnotes
Footnotes
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yosef-2016-bcl-w-bcl-xl-senolytic · doi:10.1038/ncomms11190 · Yosef R, Pilpel N, Tokarsky-Amiel R et al. · in-vitro + in-vivo · model: IMR-90 human lung fibroblasts (DIS/etoposide, RS/replicative, and OIS/H-RasV12 senescence); MEFs; mouse lung irradiation (n=5/group; 8 Gy, young male mice) + K5-rtTA/tet-p14ARF transgenic epidermal model (young mice) · key finding: BCL-W + BCL-xL dual siRNA knockdown caused ~53% reduction in DIS IMR-90 cell viability (each alone insufficient); BCL-2 only minor additive role; ABT-199 (venetoclax, BCL-2-selective) insufficient in DIS/MEF senescent cells; ABT-737 eliminates senescent cells in vivo in young-mouse irradiation and p14ARF transgenic skin models · locally downloaded (PDF confirmed) ↩ ↩2 ↩3 ↩4 ↩5
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zhu-2016-navitoclax-senolytic · doi:10.1111/acel.12445 · Zhu Y, Doornebal EJ, Pirtskhalava T et al. · in-vitro · model: IMR-90 human lung fibroblasts (10 Gy radiation-induced senescence), HUVECs (10 Gy), primary human preadipocytes (10 Gy); n=5 replicates/group (HUVEC, IMR-90); n=4 subjects (preadipocytes) · key finding (Fig 4A–B): triple BCL-2 + BCL-xL + BCL-w siRNA required for IMR-90 senolysis; BCL-xL siRNA alone (or + BCL-2) senolytic in HUVECs but insufficient for IMR-90; BCL-w co-knockdown required for IMR-90 senolysis; navitoclax (N) senolytic in HUVECs and IMR-90 but not preadipocytes; BCL-2 + BCL-xL + BCL-1 (MCL-1) triple (targets of TW-37) was not senolytic; preadipocytes require a non-BCL-2-family SCAP · locally downloaded (PDF confirmed) ↩ ↩2 ↩3 ↩4 ↩5
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PMID:8761287 (no DOI; Oncogene 1996, 13(4):665–675) · Gibson L, Holmgreen SP, Huang DCS et al. · in-vitro (cloning/expression) · model: PCR-based cloning from cDNA library + transfected mammalian cells (lymphoid/myeloid) · original cloning of BCL-W as a novel BCL-2 family member; showed BCL-W promotes cell survival against cytotoxic stimuli; broad mRNA expression across murine tissues including brain, testis, heart, kidney; rare in B/T lymphoid lines · not locally downloaded (no DOI; closed-access) no-fulltext-access — NOTE: The DOI 10.1006/cyto.1996.0066 previously cited here maps to an unrelated IL-2/macrophage paper in Cytokine and has been removed. Correct citation is PMID:8761287. ↩
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doi:10.1073/pnas.95.21.12424 · Print CG, Loveland KL, Gibson L et al. · in-vivo · model: Bcl2l2-/- mice (gene-targeted C57BL/6 background) · key finding: BCL-W-null mice are viable but male-sterile; spermatogenic defect with postmitotic Sertoli cell survival dependence; female fertility intact; no other major phenotype · not locally downloaded (status: not_oa) no-fulltext-access ↩
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chen-2005-bh3-affinities · doi:10.1016/j.molcel.2004.12.030 · Chen L, Willis SN, Wei A et al. · in-vitro (surface plasmon resonance competition assay on Biacore) · model: purified recombinant BCL-2 family proteins (C-terminal truncations) + synthetic BH3 peptides · key finding (Fig 3A): BCL-W IC50s — BIM 4.3 nM, PUMA 5.1 nM, BMF 9.8 nM, BAD 30 nM, HRK 49 nM, BID 40 nM, NOXA >100,000 nM (>100 μM); defines the broad-spectrum (BCL-2/BCL-xL/BCL-W) vs narrow-spectrum (MCL-1/A1) anti-apoptotic layers; assay variation <2-fold across replicate experiments · locally downloaded (PDF confirmed) — Correction: prior versions of this page listed BAD ~5 nM, BID ~5 nM, BMF ~5 nM for BCL-W; these are incorrect; actual values from Fig 3A are BAD 30 nM, BID 40 nM, BMF 9.8 nM ↩ ↩2 ↩3
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zhu-2015-scap-senolytics · doi:10.1111/acel.12344 · Zhu Y, Tchkonia T, Pirtskhalava T et al. · in-vitro + in-vivo · model: primary human preadipocytes + HUVECs (siRNA screen); progeroid Ercc1−/Δ and chronologically aged C57BL/6 mice · key finding: BCL-xL dominant SCAP node in HUVECs; preadipocyte SCAP is EFNB1/EFNB3/PI3KCD/p21/PAI-2 (not BCL-2 family); dasatinib + quercetin senolytic in vivo · locally downloaded (PDF confirmed) ↩
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doi:10.1038/nm.4010 · Chang J, Wang Y, Shao L et al. · in-vivo · model: 24-month-old C57BL/6 mice; oral navitoclax · key finding: navitoclax depletes senescent cells from bone marrow and muscle, rejuvenating HSCs and muscle stem cells; first in-vivo navitoclax senolytic study in aged mice · not locally downloaded (DOI lookup failed; green OA, no PMC entry) no-fulltext-access ↩
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doi:10.18632/aging.101202 · Zhu Y, Doornebal EJ, Pirtskhalava T et al. · in-vitro · n=5 replicates per concentration (HUVEC/IMR90); 4 subjects (preadipocytes) · model: 10 Gy radiation-induced senescent HUVECs, IMR90, primary preadipocytes; also fisetin tested · key finding: A1331852 and A1155463 (BCL-xL-selective) are senolytic in both HUVECs and IMR-90 cells (significantly reduced senescent cell ATP, crystal violet survival, and induced caspase 3/7) but NOT in primary preadipocytes; fisetin senolytic in HUVECs but not IMR-90 or preadipocytes · locally downloaded (PDF confirmed) ↩