BCL2

Summary

BCL2 (BCL2 apoptosis regulator, HGNC:990) is a protein-coding gene on chromosome 18q21.33, encoding Apoptosis regulator Bcl-2 (P10415). Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. In precision oncology, BCL2 G101V is associated with resistance to Venetoclax in Chronic Lymphocytic Leukemia (CIViC Level B); 3 further curated variant–drug associations are listed below.

This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 596 — RefSeq curated summary.

At a glance

• GWAS associations: 108
• Clinical variants (ClinVar): 32 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_000633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:990
Approved symbol	BCL2
Name	BCL2 apoptosis regulator
Location	18q21.33
Locus type	gene with protein product
Status	Approved
Aliases	Bcl-2, PPP1R50
Ensembl gene	ENSG00000171791
Ensembl biotype	protein_coding
OMIM	151430
Entrez	596

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000333681, ENST00000398117, ENST00000589955, ENST00000590515, ENST00000677227, ENST00000677635, ENST00000678134, ENST00000678301, ENST00000678349

RefSeq mRNA: 2 — MANE Select: NM_000633 NM_000633, NM_000657

CCDS: CCDS11981, CCDS45882

Canonical transcript exons

ENST00000333681 — 3 exons

Exon	Start	End
ENSE00001230844	63318082	63318952
ENSE00001316245	63123346	63128759
ENSE00002840278	63319174	63319769

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2807 / max 509.0052, expressed in 1207 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172268	6.4901	1008
172267	3.3875	719
172263	1.8430	376
172265	1.1018	373
172269	0.5864	288
172245	0.4148	91
172244	0.3462	80
172251	0.3267	99
172266	0.2158	123
172241	0.2131	95

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.44	gold quality
superficial temporal artery	UBERON:0001614	90.51	gold quality
calcaneal tendon	UBERON:0003701	90.50	gold quality
cortical plate	UBERON:0005343	90.44	gold quality
colonic epithelium	UBERON:0000397	89.85	gold quality
inferior olivary complex	UBERON:0002127	89.77	gold quality
cranial nerve II	UBERON:0000941	89.75	gold quality
trigeminal ganglion	UBERON:0001675	88.60	gold quality
tendon	UBERON:0000043	88.33	gold quality
medial globus pallidus	UBERON:0002477	88.33	gold quality
lateral globus pallidus	UBERON:0002476	88.12	gold quality
globus pallidus	UBERON:0001875	87.91	gold quality
caput epididymis	UBERON:0004358	87.69	gold quality
seminal vesicle	UBERON:0000998	87.61	gold quality
tendon of biceps brachii	UBERON:0008188	87.48	gold quality
epithelium of nasopharynx	UBERON:0001951	87.32	gold quality
lymph node	UBERON:0000029	87.28	gold quality
bone marrow cell	CL:0002092	87.22	gold quality
germinal epithelium of ovary	UBERON:0001304	87.17	gold quality
thoracic mammary gland	UBERON:0005200	86.98	gold quality
mammary gland	UBERON:0001911	86.89	gold quality
sural nerve	UBERON:0015488	86.88	gold quality
dorsal root ganglion	UBERON:0000044	86.80	gold quality
thyroid gland	UBERON:0002046	86.64	gold quality
decidua	UBERON:0002450	86.31	gold quality
left lobe of thyroid gland	UBERON:0001120	86.04	gold quality
granulocyte	CL:0000094	86.00	gold quality
tibial nerve	UBERON:0001323	85.86	gold quality
nephron tubule	UBERON:0001231	85.71	gold quality
renal medulla	UBERON:0000362	85.47	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	20.29
E-GEOD-135922	yes	18.96
E-CURD-119	yes	16.99
E-CURD-114	yes	11.03
E-MTAB-9067	yes	9.83
E-CURD-112	yes	4.08
E-MTAB-6075	no	523.60
E-CURD-6	no	192.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ABL1, AP1, AR, ASCL1, ATF1, ATF2, ATF5, ATM, BACH2, BCL3, BCL6, BRD2, BRD4, CAPN3, CD27, CDX1, CDX2, CEBPA, CEBPB, CEBPG, CREB1, CREM, CTNNB1, CTNNBL1, CUX1, DDB2, DDIT3, DEK, DLX4, DNMT1, DOT1L, E2F1, EGR1, ERCC2, ESR1, ESR2, ETS1, EZH2, FLI1, FOS

miRNA regulators (miRDB)

214 targeting BCL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 40)

• Review. Regulation of BCL2 phosphorylation and its role in leukemic cell apoptosis and drug resistance. (PMID:11158204)
• expression is related to apoptosis in thymus (PMID:11642719)
• an elevated bcl-2/bax ratio in rectal carcinoma tissue specimens suggests increased tumor resistance to adjuvant radiotherapy (PMID:11759059)
• BCL2 antisense transcripts decrease intracellular Bcl-2 expression and sensitize LNCaP prostate cancer cells to apoptosis-inducing agents. (PMID:11776759)
• Cells of JM1 human cell line treated with sanguinarine expressed BCL2 protein in apoptosis and cell death. (PMID:11787859)
• OVEREXPRESSION OF BCL-2 IS ASSOCIATED WITH POOR SURVIVAL IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS (PMID:11804283)
• overexpression appears to be an early event in lung tumorigenesis; may function as a potential biomarker for the development of NSCLC (PMID:11804688)
• Protein kinase A RIalpha antisense inhibition of PC3M prostate cancer cell growth: Bcl-2 hyperphosphorylation, Bax up-regulation, and Bad-hypophosphorylation (PMID:11839683)
• GM-CSF-driven apoptosis, but not TNF-driven apoptosis was reversibly associated with bcl-2-expression (bcl-2-dependent mechanism)in acute lymphoblastic leukaemia and non-Hodgkin’s lymphoma in children. (PMID:11855781)
• AUF1 binds in vitro to bcl-2 mRNA; involvement of AUF1 in the ARE/AUBP-mediated modulation of bcl-2 mRNA decay during apoptosis (PMID:11856759)
• overexpression in regulatory volume decrease. Enhancing swelling-activated Ca(2+) entry and Cl(-) channel activity (PMID:11861644)
• The over-expression of bcl-2 in the lens epithelium of fetus and children suggests that bcl-2 might be related to the development of cataract. (PMID:11864421)
• analyzed expression in leiomyomas and myometrium from fertile and menopausal women (PMID:11867266)
• Using a recombinant vaccinia virus expressing protooncogene Bcl-2, we demonstrate opposite effects of the expressed Bcl-2 in two cell lines: apoptosis induction in BSC-40 cells and apoptosis prevention in HeLa G cells. (PMID:11871856)
• Gene expression of P-gp and P26-bcl-2 is correlated with the tumor grade level of non-Hodgkin’s lymphoma. (PMID:11877091)
• Dysregulated bcl-2 expression does not play a significant pathogenetic role in most pediatric follicular lymphomas, but does identify a subset of patients in whom disease is often disseminated and more refractory to combination chemotherapy. (PMID:11877266)
• the first report of partial trisomy 3 and Bcl-2 overexpression in type II cryoglobulinemic vasculitis associated with HCV infection (PMID:11877309)
• Bcl-2 expression is upregulated by VEGF in neuroblastoma cells. (PMID:11877669)
• Bcl-2 expression is upregulated by IGF-I in neuroblastoma cells, which are thereby protected from starvation-induced apoptosis. (PMID:11877670)
• REVIEW: gene expression regulation and role of bcl-2 in cell survival and cell cycle control in early hematopoiesis (PMID:11908736)
• Bcl-2 upregulation by HIV-1 Tat during infection of primary human macrophages in culture. (PMID:11914580)
• A functional role for the B56 alpha-subunit of protein phosphatase 2A in ceramide-mediated regulation of Bcl2 phosphorylation status and function (PMID:11929874)
• Apoptotic index (includes nick-end labeling) and bcl-2 do not correlate with key clinical data (prognosis and blood counts at diagnosis) in patients with myelodysplastic syndrome, whie p53 protein levels do. (PMID:11940482)
• expression of apoptosis-regulating proteins p53, Bcl-2, and Bax in primary resected esophageal squamous cell carcinoma (PMID:11949842)
• Expression of p53 and bcl-2 proteins in acute leukemias: an immunocytochemical study (PMID:11949843)
• expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas (PMID:11956602)
• Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes. (PMID:11959101)
• Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia. (PMID:11964319)
• IGFBP-3 inactivates Bcl-2 through serine phosphorylation. (PMID:11971816)
• bcl-2 overexpression promotes myocyte proliferation (PMID:11983915)
• The coexpression of the apoptosis-related genes bcl-2 and wt1 in predicting survival in adult acute myeloid leukemia. (PMID:11986946)
• conformational change of Bcl2 due to association with peptidyl prolyl isomerase can contribute to irreversible apoptotic signaling. (PMID:11988841)
• BCL-2 overexpression was noted in 29.4% cases of T-cell lymphoblastic lymphoma cases but was not correlated with higher rate of relapse (PMID:11999565)
• ionomycin-induced calpain activation promotes decrease of Bcl-2 proteins thereby triggering the intrinsic apoptotic pathway (PMID:12000759)
• Bcl-2 expression in lymphocytes infiltrating into the liver was investigated by immunohistochemistry (PMID:12011972)
• increased expression in renal cell carcinoma associated with minimal apoptosis levels; may play role in progression of renal cell carcinomas and resistance to treatment (PMID:12025227)
• overexpressed in acute myeloid luekemia while translocations associated with this gene are absent (PMID:12031912)
• NF-kappaB activates Bcl-2 expression in t(14;18) lymphoma cells. (PMID:12032828)
• Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells (PMID:12032841)
• compared rates of bcl-2 translocation in follicular lymphoma across geographic regions (PMID:12036852)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcl2b	ENSDARG00000089109
danio_rerio	bcl2a	ENSDARG00000094704
mus_musculus	Bcl2	ENSMUSG00000057329
rattus_norvegicus	Bcl2	ENSRNOG00000077679

Paralogs (8): BAK1 (ENSG00000030110), BAX (ENSG00000087088), BCL2L2 (ENSG00000129473), BCL2L10 (ENSG00000137875), BCL2A1 (ENSG00000140379), MCL1 (ENSG00000143384), BCL2L1 (ENSG00000171552), BOK (ENSG00000176720)

Protein

Protein identifiers

Apoptosis regulator Bcl-2 — P10415 (reviewed: P10415)

All UniProt accessions (5): P10415, A0A7I2V3S7, A0A7I2V4W1, A0A7I2V5Q7, A0A7I2V5Q9

UniProt curated annotations — full annotation on UniProt →

Function. Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. 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). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function. May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release.

Subunit / interactions. Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity. Part of a complex composed of SEPTIN4 isoform ARTS, XIAP and BCL2, within the complex interacts (via BH3 domain) with SEPTIN4 isoform ARTS and XIAP, SEPTIN4 isoform ARTS acts as a scaffold protein and stabilizes the complex. Component of the complex, at least composed of LRPPRC, BECN1 and BCL2; the interactions prevent BECN1 from forming an autophagy-inducing complex with PIK3C3. Interacts with EI24. Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the ‘Ser-338’ and ‘Ser-339’ phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with RTL10/BOP. Interacts with the SCF(FBXO10) complex. Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV. Interacts with GIMAP3/IAN4, GIMAP4/IAN1 and GIMAP5/IAN5. Interacts with BCAP31. Interacts with IRF3; the interaction is inhibited by Sendai virus infection. Interacts with BECN1; thereby inhibiting autophagy in non-starvation conditions. Interacts with AMBRA1; thereby inhibiting autophagy. (Microbial infection) Interacts with Toxoplasma gondii ROP17; the interaction probably promotes BCL2 phosphorylation and degradation.

Subcellular location. Mitochondrion outer membrane. Nucleus membrane. Endoplasmic reticulum membrane. Cytoplasm.

Tissue specificity. Expressed in a variety of tissues.

Post-translational modifications. Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, which stimulates starvation-induced autophagy. Dephosphorylated by protein phosphatase 2A (PP2A). Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity. Monoubiquitinated by PRKN, leading to an increase in its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome. Ubiquitinated by XIAP, leading to its degradation by the proteasome.

Disease relevance. A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.

Domain organisation. BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity. The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3. The loop between motifs BH4 and BH3 is required for the interaction with NLRP1. The BH3 domain is required for interaction with SEPTIN4 isoform ARTS and thereby for XIAP-mediated ubiquitination and subsequent induction of apoptosis.

Similarity. Belongs to the Bcl-2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P10415-1	Alpha	yes
P10415-2	Beta

RefSeq proteins (2): NP_000624, NP_000648 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002475	Bcl2-like	Family
IPR003093	Bcl2_BH4	Domain
IPR004725	Bcl2/BclX	Family
IPR013278	Apop_reg_Bcl2	Family
IPR020717	Bcl2_BH1_motif_CS	Conserved_site
IPR020726	Bcl2_BH2_motif_CS	Conserved_site
IPR020728	Bcl2_BH3_motif_CS	Conserved_site
IPR020731	Bcl2_BH4_motif_CS	Conserved_site
IPR026298	Bcl-2_fam	Family
IPR036834	Bcl-2-like_sf	Homologous_superfamily
IPR046371	Bcl-2_BH1-3	Domain

Pfam: PF00452, PF02180

UniProt features (53 total): mutagenesis site 13, helix 11, sequence conflict 7, sequence variant 4, short sequence motif 4, modified residue 3, turn 3, region of interest 2, chain 1, transmembrane region 1, splice variant 1, strand 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

55 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8HTS	X-RAY DIFFRACTION	1.25
6GL8	X-RAY DIFFRACTION	1.4
6QGG	X-RAY DIFFRACTION	1.5
8HTR	X-RAY DIFFRACTION	1.6
6O0K	X-RAY DIFFRACTION	1.62
9O14	X-RAY DIFFRACTION	1.73
9O16	X-RAY DIFFRACTION	1.73
6O0M	X-RAY DIFFRACTION	1.75
5VAU	X-RAY DIFFRACTION	1.75
8VWX	X-RAY DIFFRACTION	1.77
6O0P	X-RAY DIFFRACTION	1.8
6QGK	X-RAY DIFFRACTION	1.8
8HOG	X-RAY DIFFRACTION	1.8
5VAY	X-RAY DIFFRACTION	1.8
7YA5	X-RAY DIFFRACTION	1.85
4LXD	X-RAY DIFFRACTION	1.9
6QG8	X-RAY DIFFRACTION	1.9
6QGJ	X-RAY DIFFRACTION	1.9
8HOH	X-RAY DIFFRACTION	1.9
9O15	X-RAY DIFFRACTION	1.99
6O0O	X-RAY DIFFRACTION	2
5VAX	X-RAY DIFFRACTION	2
6QGH	X-RAY DIFFRACTION	2
4LVT	X-RAY DIFFRACTION	2.05
7LHB	X-RAY DIFFRACTION	2.07
4MAN	X-RAY DIFFRACTION	2.07
7Y90	X-RAY DIFFRACTION	2.09
8VXN	X-RAY DIFFRACTION	2.09
2W3L	X-RAY DIFFRACTION	2.1
4IEH	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10415-F1	74.21	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 34–35 (cleavage; by caspase-3)

Post-translational modifications (3): 69, 70, 87

Mutagenesis-validated functional residues (13):

Position	Phenotype
34	abolishes cleavage by caspase-3.
64	no effect on cleavage by caspase-3.
138–141	loss of bax-binding and of anti-apoptotic activity.
144	loss of bax-binding and of anti-apoptotic activity; when associated with a-145 and a146.
145	loss of bax-binding and of anti-apoptotic activity. no effect on nlrp1-induced il1b release, nor on homodimerization. lo
145	loss of bax-binding and of anti-apoptotic activity. no effect on homodimerization.
146	loss of bax-binding and of anti-apoptotic activity; when associated with a-144 and a145.
188	loss of bax-binding and of anti-apoptotic activity. no effect on homodimerization.
190	partial loss of bax-binding and 50% decrease in anti-apoptotic activity; when associated with a-191 and a-192. no effect
191	no effect on bax-binding, nor on anti-apoptotic activity. partial loss of bax-binding and 50% decrease in anti-apoptotic
192	partial loss of bax-binding and 50% decrease in anti-apoptotic activity; when associated with l-190 and a-191. no effect
194–197	loss of bax-binding and of anti-apoptotic activity. may also affect protein stability.
200	partial loss of bax-binding and 50% decrease in anti-apoptotic activity.

Function

Pathways and Gene Ontology

Reactome pathways

30 pathways

ID	Pathway
R-HSA-111447	Activation of BAD and translocation to mitochondria
R-HSA-111453	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-844455	The NLRP1 inflammasome
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9818030	NFE2L2 regulating tumorigenic genes
R-HSA-9824594	Regulation of MITF-M-dependent genes involved in apoptosis
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-114452	Activation of BH3-only proteins
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168643	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-2262752	Cellular responses to stress
R-HSA-449147	Signaling by Interleukins
R-HSA-5357801	Programmed Cell Death
R-HSA-622312	Inflammasomes
R-HSA-8939211	ESR-mediated signaling
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-9759194	Nuclear events mediated by NFE2L2
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 1031 (showing top): MORF_RAGE, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, ZHAN_LATE_DIFFERENTIATION_GENES_UP

GO Biological Process (157): G1/S transition of mitotic cell cycle (GO:0000082), protein polyubiquitination (GO:0000209), ossification (GO:0001503), ovarian follicle development (GO:0001541), metanephros development (GO:0001656), branching involved in ureteric bud morphogenesis (GO:0001658), behavioral fear response (GO:0001662), B cell homeostasis (GO:0001782), B cell apoptotic process (GO:0001783), release of cytochrome c from mitochondria (GO:0001836), regulation of cell-matrix adhesion (GO:0001952), lymphoid progenitor cell differentiation (GO:0002320), B cell lineage commitment (GO:0002326), negative regulation of B cell apoptotic process (GO:0002903), response to ischemia (GO:0002931), renal system process (GO:0003014), melanin metabolic process (GO:0006582), regulation of nitrogen utilization (GO:0006808), autophagy (GO:0006914), apoptotic process (GO:0006915), humoral immune response (GO:0006959), DNA damage response (GO:0006974), actin filament organization (GO:0007015), axonogenesis (GO:0007409), female pregnancy (GO:0007565), positive regulation of cell population proliferation (GO:0008284), male gonad development (GO:0008584), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), response to radiation (GO:0009314), response to xenobiotic stimulus (GO:0009410), response to toxic substance (GO:0009636), post-embryonic development (GO:0009791), response to iron ion (GO:0010039), response to UV-B (GO:0010224), response to gamma radiation (GO:0010332), regulation of gene expression (GO:0010468), negative regulation of autophagy (GO:0010507), negative regulation of calcium ion transport into cytosol (GO:0010523)

GO Molecular Function (13): protease binding (GO:0002020), channel activity (GO:0015267), channel inhibitor activity (GO:0016248), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), protein heterodimerization activity (GO:0046982), BH3 domain binding (GO:0051434), protein phosphatase 2A binding (GO:0051721), molecular adaptor activity (GO:0060090), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), protein phosphatase binding (GO:0019903)

GO Cellular Component (16): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), protein-containing complex (GO:0032991), myelin sheath (GO:0043209), pore complex (GO:0046930), BAD-BCL-2 complex (GO:0097138), BCL-2 complex (GO:0097148), mitochondrial membrane (GO:0031966), Bcl-2 family protein complex (GO:0097136)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Intrinsic Pathway for Apoptosis	2
Immune System	2
Activation of BH3-only proteins	1
Signaling by Interleukins	1
Inflammasomes	1
ESR-mediated signaling	1
Extra-nuclear estrogen signaling	1
Nuclear events mediated by NFE2L2	1
MITF-M-dependent gene expression	1
Programmed Cell Death	1
Apoptosis	1
Innate Immune System	1
Cellular responses to stimuli	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
cytoplasm	3
organelle membrane	3
apoptotic signaling pathway	2
binding	2
Bcl-2 family protein complex	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
protein ubiquitination	1
multicellular organismal process	1
female gonad development	1
anatomical structure development	1
kidney development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
behavioral defense response	1
fear response	1
lymphocyte homeostasis	1
lymphocyte apoptotic process	1
apoptotic mitochondrial changes	1
cell-matrix adhesion	1
regulation of cell-substrate adhesion	1
hematopoietic progenitor cell differentiation	1
B cell differentiation	1
cell fate commitment	1
B cell apoptotic process	1
regulation of B cell apoptotic process	1
negative regulation of lymphocyte apoptotic process	1
response to stress	1
system process	1
phenol-containing compound metabolic process	1
secondary metabolic process	1
pigment metabolic process	1
nitrogen utilization	1
regulation of response to nutrient levels	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1

Protein interactions and networks

STRING

7722 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCL2	TP53	P04637	999
BCL2	BECN1	Q14457	999
BCL2	BCL2L11	O43521	999
BCL2	BNIP3	Q12983	998
BCL2	PMAIP1	Q13794	997
BCL2	HRK	O00198	996
BCL2	BIK	Q13323	995
BCL2	BMF	Q96LC9	995
BCL2	VDAC1	P21796	995
BCL2	BBC3	Q96PG8	994
BCL2	ITPR1	Q14643	993
BCL2	BAG1	Q99933	993
BCL2	ITPR3	Q14573	992
BCL2	BNIP3L	O60238	992
BCL2	APAF1	O14727	992

IntAct

217 interactions, top by confidence:

A	B	Type	Score
TP53	MDM4	psi-mi:“MI:0914”(association)	0.970
MDM4	TP53	psi-mi:“MI:0914”(association)	0.970
BAX	BCL2	psi-mi:“MI:0403”(colocalization)	0.950
BAX	BCL2	psi-mi:“MI:0915”(physical association)	0.950
BECN1	BCL2	psi-mi:“MI:0914”(association)	0.950
BCL2	BECN1	psi-mi:“MI:0915”(physical association)	0.950
BCL2	BAX	psi-mi:“MI:0915”(physical association)	0.950
BCL2	BAX	psi-mi:“MI:0403”(colocalization)	0.950
BAX	BCL2	psi-mi:“MI:0914”(association)	0.950
BECN1	BCL2	psi-mi:“MI:0915”(physical association)	0.950
BCL2	BECN1	psi-mi:“MI:0914”(association)	0.950
BAX	BCL2L11	psi-mi:“MI:0914”(association)	0.940
BCL2L11	BCL2	psi-mi:“MI:0407”(direct interaction)	0.930
BCL2	BCL2L11	psi-mi:“MI:0914”(association)	0.930
BCL2L11	BCL2	psi-mi:“MI:0915”(physical association)	0.930

BioGRID (404): BCL2 (Co-purification), BCL2 (Reconstituted Complex), BCL2 (Reconstituted Complex), TP53BP2 (Protein-peptide), NR4A1 (Affinity Capture-Western), NR4A1 (Reconstituted Complex), BCL2 (Affinity Capture-Western), BCL2 (Reconstituted Complex), BCL2L1 (Reconstituted Complex), BCL2 (Affinity Capture-Western), BID (Affinity Capture-Western), BID (Co-fractionation), BCL2 (Reconstituted Complex), BCL2 (Reconstituted Complex), BCL2 (Affinity Capture-Luminescence)

ESM2 similar proteins: A1A5B6, A2A8U2, A2SXS5, A4D2P6, O00255, O02718, O88559, P10415, P10417, P12755, P36956, P49950, P85299, Q00709, Q0D2I5, Q0P5I0, Q16611, Q2KJ58, Q3MII6, Q504T8, Q50H33, Q5FVG6, Q5SNT2, Q60698, Q68FE7, Q6DVA0, Q6NS60, Q6R755, Q6WVG3, Q6ZWB6, Q80U62, Q812A5, Q86TM6, Q8BXL9, Q8C190, Q8K2Y3, Q8NC56, Q8R1F1, Q8TF61, Q8VDV3

Diamond homologs: O02703, O02718, O77737, P10415, P10417, P49950, P53563, P70345, Q00709, Q07812, Q07813, Q07816, Q07817, Q07820, Q1RMX3, Q45T69, Q63690, Q64373, Q6R755, Q7YRZ9, Q90343, Q91827, Q92843, Q9JJV8, O08734, Q07440, Q07818, Q16548, Q16611, Q3C2I0, Q91828, P0C8H4, P0C8H5, P0C8H6, P42485, Q07819, Q90ZN1, Q8HYS5, Q9HBF5, P97287

SIGNOR signaling

85 interactions.

A	Effect	B	Mechanism
BBC3	“down-regulates activity”	BCL2	binding
BAD	“down-regulates activity”	BCL2	relocalization
BCL2L11	“down-regulates activity”	BCL2	binding
BCL2L11	down-regulates	BCL2	binding
MAPK14	“down-regulates activity”	BCL2	phosphorylation
NOTCH1	“up-regulates quantity by expression”	BCL2	“transcriptional regulation”
ABT-737	down-regulates	BCL2	“chemical inhibition”
BCL2	down-regulates	BAK1	binding
BCL2	down-regulates	BECN1	binding
FOXA1	“down-regulates quantity by repression”	BCL2	“transcriptional regulation”
MAPK8	up-regulates	BCL2	phosphorylation
MAPK8	“down-regulates activity”	BCL2	phosphorylation
MAPK8	down-regulates	BCL2	phosphorylation
PPP2R5B	down-regulates	BCL2	dephosphorylation
4-[4-[[2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexenyl]methyl]-1-piperazinyl]-N-[4-[[(2R)-4-(4-morpholinyl)-1-(phenylthio)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	down-regulates	BCL2	“chemical inhibition”
“Obatoclax mesylate”	down-regulates	BCL2	“chemical inhibition”
gossypol	down-regulates	BCL2	“chemical inhibition”
Obatoclax	down-regulates	BCL2	“chemical inhibition”
N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamide	down-regulates	BCL2	“chemical inhibition”
NOXA1	“down-regulates activity”	BCL2
ERK1/2	“up-regulates quantity by stabilization”	BCL2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BH3-only proteins	9	109.0×	4e-15
Intrinsic Pathway for Apoptosis	14	100.0×	3e-23
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	7	92.8×	4e-11
TP53 Regulates Transcription of Cell Death Genes	6	79.6×	5e-09
Apoptosis	15	61.4×	1e-21
Programmed Cell Death	15	53.6×	7e-21
Transcriptional Regulation by TP53	8	12.1×	1e-05
Signaling by Interleukins	6	9.4×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of release of cytochrome c from mitochondria	11	165.2×	3e-20
release of cytochrome c from mitochondria	8	110.1×	5e-13
apoptotic mitochondrial changes	5	87.0×	2e-07
positive regulation of intrinsic apoptotic signaling pathway	9	85.0×	2e-13
intrinsic apoptotic signaling pathway	9	63.3×	2e-12
regulation of mitochondrial membrane potential	5	53.3×	2e-06
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	5	47.2×	3e-06
positive regulation of protein-containing complex assembly	7	46.3×	1e-08

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — DLBCLNOS, MLYM, NHL.

Clinical variants and AI predictions

ClinVar

32 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	13
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
253425	GRCh37/hg19 18q21.32-22.2(chr18:58014591-68158862)x1	Pathogenic
155128	GRCh38/hg38 18q21.32-22.3(chr18:59909593-72609801)x3	Likely pathogenic

SpliceAI

1722 predictions. Top by Δscore:

Variant	Effect	Δscore
18:63148494:G:C	donor_gain	1.0000
18:63148498:AAT:A	donor_gain	1.0000
18:63124145:A:C	acceptor_gain	0.9900
18:63124138:C:CT	acceptor_gain	0.9800
18:63180313:AAAAT:A	donor_gain	0.9800
18:63319915:T:TA	donor_gain	0.9800
18:63319918:T:TA	donor_gain	0.9800
18:63124139:A:T	acceptor_gain	0.9700
18:63124174:T:A	acceptor_gain	0.9700
18:63186936:AG:A	donor_gain	0.9700
18:63124133:T:TC	acceptor_gain	0.9600
18:63148500:T:TA	donor_gain	0.9600
18:63148526:TTCA:T	donor_gain	0.9600
18:63319904:AC:A	donor_gain	0.9600
18:63319905:CC:C	donor_gain	0.9600
18:63124133:T:C	acceptor_gain	0.9500
18:63124138:C:T	acceptor_gain	0.9500
18:63124145:A:AC	acceptor_gain	0.9500
18:63128760:C:G	acceptor_loss	0.9500
18:63128761:T:A	acceptor_loss	0.9500
18:63148498:AATC:A	donor_gain	0.9500
18:63186936:AGC:A	donor_gain	0.9500
18:63186937:G:C	donor_gain	0.9500
18:63318084:AG:A	donor_gain	0.9500
18:63128758:TC:T	acceptor_gain	0.9400
18:63128759:CC:C	acceptor_gain	0.9400
18:63318094:AT:A	donor_gain	0.9400
18:63318267:C:CT	donor_gain	0.9400
18:63319314:C:CT	acceptor_gain	0.9400
18:63124173:C:CA	acceptor_gain	0.9300

AlphaMissense

1543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:63318082:C:A	W195C	1.000
18:63318082:C:G	W195C	1.000
18:63318084:A:G	W195R	1.000
18:63318084:A:T	W195R	1.000
18:63318103:C:A	W188C	1.000
18:63318103:C:G	W188C	1.000
18:63318208:G:C	F153L	1.000
18:63318208:G:T	F153L	1.000
18:63318210:A:G	F153L	1.000
18:63318230:C:A	R146M	1.000
18:63318235:C:A	W144C	1.000
18:63318235:C:G	W144C	1.000
18:63318237:A:G	W144R	1.000
18:63318237:A:T	W144R	1.000
18:63318253:G:C	F138L	1.000
18:63318253:G:T	F138L	1.000
18:63318255:A:G	F138L	1.000
18:63128666:C:G	G227R	0.999
18:63128666:C:T	G227R	0.999
18:63318083:C:G	W195S	0.999
18:63318101:A:G	I189T	0.999
18:63318105:A:G	W188R	0.999
18:63318105:A:T	W188R	0.999
18:63318125:A:G	L181P	0.999
18:63318137:A:C	M177R	0.999
18:63318141:A:G	W176R	0.999
18:63318141:A:T	W176R	0.999
18:63318184:G:C	S161R	0.999
18:63318184:G:T	S161R	0.999
18:63318186:T:G	S161R	0.999

dbSNP variants (sampled 300 via entrez): RS1000023499 (18:63156103 A>T), RS1000050149 (18:63307166 CTT>C), RS1000050989 (18:63265988 C>T), RS1000066767 (18:63192605 G>C), RS1000077846 (18:63141825 A>C), RS1000084987 (18:63281490 C>A), RS1000110025 (18:63259424 C>T), RS1000136544 (18:63239918 G>A,T), RS1000140970 (18:63272333 C>G,T), RS1000144522 (18:63307394 A>G), RS1000157797 (18:63304625 C>T), RS1000158986 (18:63133472 G>A,T), RS1000175008 (18:63263504 T>A,C), RS1000203802 (18:63230973 C>T), RS1000217941 (18:63297798 T>A,C)

Disease associations

OMIM: gene MIM:151430 | disease phenotypes: MIM:614080

GenCC curated gene-disease

Mondo (1): multiple congenital anomalies-hypotonia-seizures syndrome 1 (MONDO:0013563)

Orphanet (1): Multiple congenital anomalies-hypotonia-seizures syndrome (Orphanet:280633)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0001004	Lymphedema
HP:0001287	Meningitis
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001945	Fever
HP:0002202	Pleural effusion
HP:0002585	Abnormal peritoneum morphology
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0003072	Hypercalcemia
HP:0012378	Fatigue
HP:0025435	Increased circulating lactate dehydrogenase concentration
HP:0030166	Night sweats
HP:0033823	Mediastinal mass
HP:0100721	Mediastinal lymphadenopathy
HP:0200036	Skin nodule

GWAS associations

108 associations (top):

Study	Trait	p-value
GCST001776_9	Cardiac Troponin-T levels	7.000000e-06
GCST002073_1	Chronic lymphocytic leukemia	8.000000e-11
GCST002073_4	Chronic lymphocytic leukemia	3.000000e-12
GCST002379_6	Pyoderma gangrenosum in inflammatory bowel disease	2.000000e-06
GCST002643_5	Follicular lymphoma	8.000000e-10
GCST002782_108	Waist-to-hip ratio adjusted for body mass index	1.000000e-09
GCST002782_109	Waist-to-hip ratio adjusted for body mass index	3.000000e-09
GCST002783_365	Body mass index	6.000000e-06
GCST003128_2	Adolescent idiopathic scoliosis	2.000000e-12
GCST003468_19	Chronic lymphocytic leukemia	4.000000e-11
GCST003658_3	Modified Stumvoll Insulin Sensitivity Index (model adjusted for BMI)	2.000000e-08
GCST003659_5	Modified Stumvoll Insulin Sensitivity Index (BMI interaction)	3.000000e-08
GCST004146_21	Chronic lymphocytic leukemia	2.000000e-11
GCST004505_16	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	7.000000e-06
GCST004599_133	Mean platelet volume	8.000000e-14
GCST004600_101	Eosinophil percentage of white cells	2.000000e-20
GCST004601_182	Red blood cell count	1.000000e-18
GCST004602_255	Mean corpuscular volume	8.000000e-21
GCST004603_188	Platelet count	1.000000e-10
GCST004606_35	Eosinophil count	7.000000e-25
GCST004607_11	Plateletcrit	9.000000e-31
GCST004609_88	Monocyte percentage of white cells	7.000000e-13
GCST004611_140	High light scatter reticulocyte count	5.000000e-10
GCST004617_127	Eosinophil percentage of granulocytes	1.000000e-18
GCST004618_21	White blood cell count (basophil)	1.000000e-51
GCST004622_66	Reticulocyte count	5.000000e-11
GCST004623_88	Neutrophil percentage of granulocytes	4.000000e-27
GCST004624_16	Sum eosinophil basophil counts	3.000000e-37
GCST004625_202	Monocyte count	3.000000e-20
GCST004627_179	Lymphocyte count	2.000000e-10

EFO canonical traits (35, from GWAS)

EFO ID	Trait name
EFO:0005043	cardiac troponin T measurement
EFO:0006835	pyoderma gangrenosum
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004340	body mass index
EFO:0004471	insulin sensitivity measurement
EFO:0004318	smoking behavior
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0007989	monocyte percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0005128	albumin:globulin ratio measurement
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004653	response to TNF antagonist
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (9): CHEMBL3885513 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885516 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523685 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748224 (PROTEIN-PROTEIN INTERACTION), CHEMBL4860 (SINGLE PROTEIN), CHEMBL5169264 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169265 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169266 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066579 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 98,833 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201752	IXABEPILONE	4	25,437
CHEMBL3137309	VENETOCLAX	4	9,389
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL408194	OBATOCLAX	3	2,914
CHEMBL443684	NAVITOCLAX	3	4,791
CHEMBL51483	GOSSYPOL	3	13,973
CHEMBL5314951	SONROTOCLAX	3	3
CHEMBL22150	CHLORCYCLIZINE	2	4,290
CHEMBL242341	FORMONONETIN	2	8,420
CHEMBL5314523	LACUTOCLAX	2	17
CHEMBL376408	ABT 737	1	4,288
CHEMBL3701382	VOB-560	1	84
CHEMBL4297482	AZD-5991	1	947
CHEMBL4446378	TAPOTOCLAX	1	1,476

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 10 curated evidence items; also 2 diagnostic, 2 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
BCL2 G101V	Venetoclax	Chronic Lymphocytic Leukemia	Resistance	CIViC B	EID8174 +5
BCL2 F104I	Venetoclax	Follicular Lymphoma	Resistance	CIViC C	EID8375 +1
BCL2 G101V	Venetoclax	Chronic Lymphocytic Leukemia/small Lymphocytic Lymphoma	Resistance	CIViC C	EID8185
BCL2 Overexpression	Venetoclax + Dinaciclib	Lymphoma	Resistance	CIViC D	EID9313

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1800477	Efficacy	3	interferons;ribavirin	Hepatitis C virus infection
rs2849380	Toxicity	3	carboplatin;docetaxel;paclitaxel	Ovarian Neoplasms

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800477	BCL2	3	2.00	1	interferons;ribavirin
rs2849380	BCL2	3	3.00	1	carboplatin;docetaxel;paclitaxel

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — B-cell lymphoma 2 (Bcl-2) protein family

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
venetoclax	Antagonist	11.0	pKi
sonrotoclax	Antagonist	10.72	pIC50
lisaftoclax	Antagonist	10.0	pKi
AZD4320	Antagonist	9.52	pIC50
APG-1252-M1	Antagonist	9.35	pKi
navitoclax	Antagonist	9.0	pKi
ABT-737	Antagonist	9.0	pKi
obatoclax	Antagonist	5.96	pKi

Binding affinities (BindingDB)

2267 measured of 2601 human assays (2602 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[1-(1,3-difluoropropan-2-yl)piperidin-4-yl]methoxy]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.002 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
2-(3-chlorophenoxy)-4-[4-[[2-(4-chlorophenyl)-5-[2-(dimethylamino)ethoxy]phenyl]methyl]piperazin-1-yl]-N-[4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl]sulfonylbenzamide	KI	0.005 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
2-[(6-amino-5-chloro-3-pyridinyl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-methoxycyclohexyl)methylamino]-3-nitrophenyl]sulfonylbenzamide	KI	0.005 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
2-[(6-amino-5-chloro-3-pyridinyl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl]sulfonylbenzamide	KI	0.009 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-[(6,7-difluoro-1H-indol-5-yl)oxy]-N-[3-nitro-4-[[1-(oxan-4-yl)piperidin-4-yl]amino]phenyl]sulfonylbenzamide	KI	0.01 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-methoxycyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.01 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[8-(4-chlorophenyl)spiro[4.5]dec-8-en-9-yl]methyl]piperazin-1-yl]-N-[4-[(4-morpholin-4-ylcyclohexyl)amino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.01 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-cyclopropylmorpholin-2-yl)methoxy]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.01 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
trans-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.01 nM	US-10213433
trans-4-(4-{[8-(4-chlorophenyl)spiro[4.5]dec-7-en-7-yl]methyl}piperazin-1-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3-nitrophenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.01 nM	US-10213433
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(2,2,2-trifluoroethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.011 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[[5-chloro-6-[(4-methoxycyclohexyl)methoxy]-3-pyridinyl]sulfonyl]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.011 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
trans-N-({5-chloro-6-[(4-methoxycyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.011 nM	US-10213433
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl]sulfonylbenzamide	KI	0.012 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
2-[(6-amino-5-bromo-3-pyridinyl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-methoxycyclohexyl)methylamino]-3-nitrophenyl]sulfonylbenzamide	KI	0.012 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-morpholin-4-ylcyclohexyl)amino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.012 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[4-(4-chlorophenyl)-6,6-dimethyl-2,5-dihydropyran-3-yl]methyl]piperazin-1-yl]-N-[4-(oxan-4-ylmethylamino)-3-(trifluoromethylsulfonyl)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.012 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-(4-morpholin-4-ylbut-2-ynoxy)-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.012 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
cis-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3-nitrophenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.012 nM	US-10213433
2-(2-chlorophenoxy)-4-[4-[[4-(4-chlorophenyl)-6,6-dimethyl-2,5-dihydropyran-3-yl]methyl]piperazin-1-yl]-N-[4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl]sulfonylbenzamide	KI	0.013 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-indol-5-yloxy)-N-[4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl]sulfonylbenzamide	KI	0.013 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-[[1-(oxan-4-yl)piperidin-4-yl]amino]phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.013 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-cyclopropylmorpholin-2-yl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.013 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-hydroxy-4-methylcyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.013 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[[5-chloro-6-[(4-hydroxy-4-methylcyclohexyl)methoxy]-3-pyridinyl]sulfonyl]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.013 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(cis-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.013 nM	US-10213433
N-({5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.013 nM	US-10213433
2-[(6-amino-5-chloro-3-pyridinyl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-[[1-(oxetan-3-yl)piperidin-4-yl]amino]phenyl]sulfonylbenzamide	KI	0.014 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
2-[(6-amino-5-chloro-3-pyridinyl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-cyclopropylmorpholin-2-yl)methylamino]-3-nitrophenyl]sulfonylbenzamide	KI	0.014 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[1-(1,3-difluoropropan-2-yl)piperidin-4-yl]amino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[[5-chloro-6-[(4-fluorooxan-4-yl)methoxy]-3-pyridinyl]sulfonyl]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[[5-chloro-6-[(1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]-3-pyridinyl]sulfonyl]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-({4-[(1S,4S)-bicyclo[2.2.1]hept-5-en-2-ylmethoxy]-3-nitrophenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-10213433
4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-10213433
N-({5-chloro-6-[(trans-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-10213433
N-[4-[[(1R,4R)-2-bicyclo[2.2.1]hept-5-enyl]amino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.014 nM	US-9125913: Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases
2-[(6-amino-5-bromo-3-pyridinyl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-(1,4-dioxan-2-ylmethylamino)-3-nitrophenyl]sulfonylbenzamide	KI	0.015 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[[5-chloro-6-[[(2S)-4-[2-(dimethylamino)acetyl]morpholin-2-yl]methoxy]-3-pyridinyl]sulfonyl]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.015 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[4-[(4-hydroxy-4-methylcyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-4-[2-[(2S)-4-methyl-2-(2-propan-2-ylphenyl)piperazin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	IC50	0.015 nM	US-11420968: Bcl-2 inhibitors
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[3-(dimethylamino)propylamino]-3-nitrophenyl]sulfonyl-2-(3-fluorophenoxy)benzamide	KI	0.016 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
2-[(6-amino-5-chloro-3-pyridinyl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(3R)-1-(2,2-difluoroethyl)pyrrolidin-3-yl]amino]-3-nitrophenyl]sulfonylbenzamide	KI	0.016 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-[[(3S)-oxan-3-yl]methylamino]phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.016 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-[[4-(oxan-4-yl)morpholin-3-yl]methoxy]phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.016 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[[5-chloro-6-[[1-[2-(dimethylamino)acetyl]piperidin-4-yl]methoxy]-3-pyridinyl]sulfonyl]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.016 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[[5-chloro-6-[(4-fluoro-1-methylpiperidin-4-yl)methoxy]-3-pyridinyl]sulfonyl]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.016 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-[3-chloro-4-[(4-hydroxy-4-methylcyclohexyl)methoxy]phenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.016 nM	US-9174982: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[3-(dimethylamino)propylamino]-3-nitrophenyl]-2-(3-fluorophenoxy)benzamide	KI	0.016 nM	US-9303025: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
N-({3-chloro-4-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	KI	0.016 nM	US-10213433
4-[4-[[4-(4-chlorophenyl)-6,6-dimethyl-2,5-dihydropyran-3-yl]methyl]piperazin-1-yl]-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonylbenzamide	KI	0.017 nM	US-8952157: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases

ChEMBL bioactivities

5940 potent at pChembl≥5 of 6100 total, top 37 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL3653966
11.00	Ki	0.01	nM	CHEMBL3985475
11.00	Ki	0.01	nM	CHEMBL3961644
11.00	Ki	0.01	nM	CHEMBL3952489
11.00	Ki	0.01	nM	A-1211212
11.00	Ki	0.01	nM	CHEMBL5955498
10.96	Ki	0.011	nM	CHEMBL3900365
10.96	Ki	0.011	nM	CHEMBL3891622
10.96	Ki	0.011	nM	CHEMBL5911102
10.92	Ki	0.012	nM	CHEMBL3650632
10.92	Ki	0.012	nM	CHEMBL3654125
10.92	Ki	0.012	nM	CHEMBL3948837
10.92	Ki	0.012	nM	CHEMBL3902290
10.92	Ki	0.012	nM	CHEMBL3963984
10.92	Ki	0.012	nM	CHEMBL5938241
10.89	Ki	0.013	nM	CHEMBL3650520
10.89	Ki	0.013	nM	CHEMBL3925316
10.89	Ki	0.013	nM	CHEMBL3916807
10.89	Ki	0.013	nM	CHEMBL3901126
10.89	Ki	0.013	nM	CHEMBL3973960
10.89	Ki	0.013	nM	CHEMBL3977292
10.89	Ki	0.013	nM	CHEMBL5990467
10.89	Ki	0.013	nM	CHEMBL5821547
10.89	Ki	0.013	nM	CHEMBL6047078
10.85	Ki	0.014	nM	CHEMBL3654122
10.85	Ki	0.014	nM	CHEMBL3654127
10.85	Ki	0.014	nM	CHEMBL4110818
10.85	Ki	0.014	nM	CHEMBL3952871
10.85	Ki	0.014	nM	CHEMBL3976783
10.85	Ki	0.014	nM	CHEMBL3901940
10.85	Ki	0.014	nM	CHEMBL3978223
10.85	Ki	0.014	nM	CHEMBL5829019
10.85	Ki	0.014	nM	CHEMBL6022358
10.85	Ki	0.014	nM	CHEMBL5930597
10.82	Ki	0.015	nM	CHEMBL3654119
10.82	Ki	0.015	nM	CHEMBL3955355
10.82	IC50	0.015	nM	CHEMBL5532549

PubChem BioAssay actives

1605 with measured affinity, of 2510 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[4-[(4-hydroxy-4-methylcyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
4-[2-[(2S)-2-[2-(dimethylamino)phenyl]pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[3-nitro-4-(3-oxabicyclo[3.1.0]hexan-6-ylmethylamino)phenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[4-[[(2S)-1,4-dioxan-2-yl]methylamino]-3-nitrophenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
4-[2-[(2S)-2-(2-ethylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[4-[[(2R)-1,4-dioxan-2-yl]methylamino]-3-nitrophenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
4-[2-[(2S)-2-(2-cyclopropylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[[5-nitro-3-(oxan-4-yl)-3,4-dihydro-2H-1,4-benzoxazin-7-yl]sulfonyl]-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[[2-(morpholin-4-ylmethyl)-7-nitro-2,3-dihydro-1H-indol-5-yl]sulfonyl]-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[[(3R)-3-(4-hydroxy-4-methylcyclohexyl)-5-nitro-3,4-dihydro-2H-1,4-benzoxazin-7-yl]sulfonyl]-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-N-[4-[[(2R,5S)-5-hydroxy-5-methyloxan-2-yl]methylamino]-3-nitrophenyl]sulfonyl-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	<0.0001	uM
4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-N-[4-[[(2S)-1,4-dioxan-2-yl]methylamino]-3-nitrophenyl]sulfonyl-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	<0.0001	uM
4-[2-[2-(2-cyclopropylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[4-(3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]furan-5-ylmethylamino)-3-nitrophenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
N-[4-[(1-methylpiperidin-4-yl)methylamino]-3-nitrophenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	<0.0001	uM
4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	1388438: Inhibition of Bcl2 (unknown origin)	ki	<0.0001	uM
4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl)amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	1580120: Inhibition of His-tagged Bcl-2 (unknown origin) incubated for 30 mins by TR-FRET assay	ki	<0.0001	uM
4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	1979308: Binding affinity to BCL2 (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
Venetoclax	1293719: Binding affinity to Bcl-2 (unknown origin) by FRET assay	ki	<0.0001	uM
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-methoxycyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	1388438: Inhibition of Bcl2 (unknown origin)	ki	<0.0001	uM
N-[3-[chloro(difluoro)methyl]sulfonyl-4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]phenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]benzamide	2187832: Binding affinity to Bcl-2 (unknown origin) assessed as dissociation constant incubated for 1 hrs by TR-FRET assay	ki	<0.0001	uM
5-[5-chloro-2-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(5-cyano-1,2-dimethylpyrrol-3-yl)-N-(4-hydroxyphenyl)-1,2-dimethylpyrrole-3-carboxamide	1853858: Binding affinity to recombinant wild-type Bcl-2 (unknown origin) using peptide probe incubated for 2 hrs by fluorescence based assay	ki	0.0001	uM
4-[2-[(2S)-2-(2-methylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
4-[2-[(2S)-2-(2-methoxyphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-yloxyphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
4-[2-[(2S)-2-(2-ethoxyphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
N-[4-[(4-methoxy-4-methylcyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
N-[[5-chloro-6-[(4-fluorooxan-4-yl)methoxy]-3-pyridinyl]sulfonyl]-4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	0.0001	uM
4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-N-[4-[(4-hydroxy-4-methylcyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	0.0001	uM
N-[3-chloro-4-[(4-hydroxy-4-methylcyclohexyl)methylamino]phenyl]sulfonyl-4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	0.0001	uM
4-[6-[2-(2-cyclopropylphenyl)pyrrolidin-1-yl]-2-azaspiro[3.3]heptan-2-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
N-[4-[(4,4-difluorocyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-4-[2-[(2S)-2-(2-propan-2-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0001	uM
2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-[4-(4-pyrazolo[3,4-d]pyrimidin-1-ylphenoxy)butyl]-1,3-thiazole-4-carboxylic acid	1168932: Inhibition of BCL-2 (unknown origin) incubated for 1 hr by TR-FRET assay	ki	0.0001	uM
4-[4-[[2-(4-chlorophenyl)-6-[2-(dimethylamino)ethoxy]phenyl]methyl]piperazin-1-yl]-2-(1H-indol-5-yloxy)-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonylbenzamide	1293719: Binding affinity to Bcl-2 (unknown origin) by FRET assay	ki	0.0001	uM
4-[2-[(2S)-2-(2-bromophenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0002	uM
4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-N-[4-[(4-hydroxyoxan-4-yl)methylamino]-3-nitrophenyl]sulfonyl-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	0.0002	uM
4-[2-[(2S)-2-[2-(methoxymethyl)phenyl]pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0002	uM
N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-4-[2-[(2S)-2-(2-pyrrolidin-1-ylphenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0002	uM
4-[4-[[8-(4-chlorophenyl)spiro[3.5]non-7-en-7-yl]methyl]piperazin-1-yl]-N-[4-[[(2S)-1,4-dioxan-2-yl]methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0003	uM
N-[4-[3-(diethylamino)propylamino]-3-nitrophenyl]sulfonyl-4-[4-[[4,4-dimethyl-2-[4-(trifluoromethyl)phenyl]cyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	1769238: Displacement of Bak derived peptide from Bcl-2 (unknown origin) measured after 15 mins by microplate reader assay	ic50	0.0003	uM
4-[4-[[2-(2-cyclopropylphenyl)pyrrolidin-1-yl]methyl]piperidin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0003	uM
4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-N-[4-[[(2R,5S)-5-methoxyoxan-2-yl]methylamino]-3-nitrophenyl]sulfonyl-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	0.0003	uM
4-[(8R,15S)-4-(4-chlorophenyl)-6,6-dimethyl-9,13-dioxa-1,17-diazatricyclo[13.4.0.03,8]nonadec-3-en-17-yl]-N-[4-[[3-fluoro-3-(methoxymethyl)cyclobutyl]methylamino]-3-nitrophenyl]sulfonyl-2-(14-oxa-2,4,10-triazatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraen-10-yl)benzamide	2016748: Inhibition of human Bcl-2 expressed in Escherichia coli BL21(DE3) T1R cells preincubated under shaking condition for 1 min and measured after 3 hrs by TR-FRET assay	ki	0.0003	uM
(3S)-6,8-dibromo-N-(4-chloro-3-nitrophenyl)sulfonyl-2-[(4-cyanophenyl)methyl]-7-[(4-phenylphenyl)methoxy]-3,4-dihydro-1H-isoquinoline-3-carboxamide	1853844: Binding affinity to Bcl-2 (unknown origin) assessed as inhibition constant using 5-FAM-QEDIIRNIARHLAQVGDSMDRSIPPG as substrate	ki	0.0004	uM
3-[6-[(3S)-3-(aminomethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-N-(4-hydroxyphenyl)-N-phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide	1580119: Inhibition of wild-type BCL-2 (unknown origin) expressed in Escherichia coli BL21 cells using biotinylated BIMBH3 or BAXBH3 peptide by surface plasmon resonance assay	ki	0.0004	uM
4-[2-[(2S)-2-(2-chlorophenyl)pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0004	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	2070106: Binding affinity to human recombinant Bcl-2 assessed as inhibition constant by fluorescence polarization assay	ki	0.0005	uM
4-[4-[[4,4-dimethyl-2-[4-(trifluoromethyl)phenyl]cyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(1-ethylpiperidin-4-yl)methoxy]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	1769238: Displacement of Bak derived peptide from Bcl-2 (unknown origin) measured after 15 mins by microplate reader assay	ic50	0.0005	uM
4-[2-[(2S)-2-[2-(2-methylpropyl)phenyl]pyrrolidin-1-yl]-7-azaspiro[3.5]nonan-7-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2071056: Inhibition of Bcl-2 (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay	ic50	0.0006	uM

CTD chemical–gene interactions

1380 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects expression, increases cleavage, increases degradation, increases response to substance, decreases reaction (+12 more)	120
Cisplatin	decreases expression, decreases reaction, affects cotreatment, increases cleavage, affects localization (+9 more)	68
Resveratrol	affects localization, increases chemical synthesis, increases cleavage, affects binding, increases activity (+9 more)	56
Quercetin	increases degradation, increases phosphorylation, increases response to substance, decreases expression, affects cotreatment (+7 more)	49
Doxorubicin	affects response to substance, increases activity, increases cleavage, increases localization, increases reaction (+9 more)	47
Acetylcysteine	decreases expression, increases reaction, increases phosphorylation, increases abundance, affects expression (+6 more)	38
Paclitaxel	increases response to substance, affects reaction, affects localization, affects phosphorylation, increases expression (+11 more)	38
Curcumin	decreases expression, decreases reaction, increases expression, increases degradation, affects expression (+6 more)	35
Tretinoin	decreases reaction, increases phosphorylation, increases expression, affects cotreatment, decreases expression (+2 more)	34
Hydrogen Peroxide	decreases expression, decreases reaction, decreases response to substance, affects cotreatment, increases expression (+4 more)	33
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases expression, affects reaction (+4 more)	29
Fluorouracil	affects expression, affects reaction, increases reaction, decreases reaction, increases expression (+5 more)	29
Estradiol	affects expression, increases reaction, affects cotreatment, affects reaction, decreases expression (+4 more)	28
1-Methyl-4-phenylpyridinium	increases expression, decreases reaction, increases reaction, affects reaction, affects expression (+1 more)	25
bisphenol A	increases activity, decreases expression, increases expression, decreases methylation, decreases reaction (+3 more)	23
Bortezomib	increases cleavage, increases expression, affects cotreatment, increases activity, affects expression (+4 more)	18
Plant Extracts	increases expression, decreases reaction, decreases response to substance, affects cotreatment, decreases expression (+2 more)	18
pyrazolanthrone	decreases expression, decreases reaction, increases phosphorylation, affects binding	16
Cadmium Chloride	affects cotreatment, affects expression, affects reaction, affects response to substance, decreases reaction (+3 more)	16
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, decreases reaction, increases cleavage, decreases response to substance, affects reaction (+6 more)	15
Vorinostat	decreases reaction, increases cleavage, affects cotreatment, decreases expression, increases expression (+3 more)	15
Tamoxifen	decreases expression, increases expression, decreases activity, increases response to substance, affects binding (+3 more)	15
(+)-JQ1 compound	affects expression, affects binding, affects cotreatment, decreases reaction, decreases expression (+2 more)	14
Benzo(a)pyrene	decreases reaction, affects cotreatment, increases expression, increases methylation, decreases expression	14
Glucose	affects cotreatment, affects binding, increases expression, increases reaction, increases degradation (+3 more)	14
Paraquat	decreases expression, decreases reaction, decreases response to substance, increases expression, increases reaction (+2 more)	14
Rotenone	affects reaction, decreases expression, decreases reaction, decreases response to substance, affects cotreatment (+2 more)	14
Cadmium	affects expression, affects cotreatment, affects reaction, decreases expression, increases expression (+4 more)	13
SB 203580	decreases expression, increases reaction, affects expression, affects reaction, decreases reaction (+2 more)	12
Aspirin	decreases expression, decreases reaction, increases expression, increases cleavage, increases reaction (+2 more)	12

ChEMBL screening assays

446 unique, capped per target: 418 binding, 23 functional, 3 toxicity, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1251004	Binding	Inhibition of GST-tagged Bcl-2/FITC-conjugated Bax interaction by fluorescence polarisation assay	Synthesis and biological activities of new di- and trimeric quinoline derivatives. — Bioorg Med Chem
CHEMBL2162638	Functional	Antagonist activity at recombinant Bcl2 assessed as restoration of BIM BH3-induced cytochrome c release in mitochondria isolated from MDA-MB-231 cells after 1 hr by Western blot analysis	Structure-based design of potent Bcl-2/Bcl-xL inhibitors with strong in vivo antitumor activity. — J Med Chem
CHEMBL4715588	ADMET	Inhibition of F-Bak binding to GST-tagged BCL2 (unknown origin) measured after 1 hr by TR-FRET assay	Structure-Based Design of A-1293102, a Potent and Selective BCL-X Inhibitor. — ACS Med Chem Lett

Cellosaurus cell lines

122 cell lines: 62 transformed cell line, 57 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0539	SU-DHL-4	Cancer cell line	Male
CVCL_1898	U-2973	Cancer cell line	Male
CVCL_2206	SU-DHL-6	Cancer cell line	Male
CVCL_5T79	RIN-5F-Bcl-2	Cancer cell line	Male
CVCL_8093	FL-18	Cancer cell line	Male
CVCL_8094	FL-218	Cancer cell line	Female
CVCL_8095	FL-318	Cancer cell line	Male
CVCL_8533	STR-428	Cancer cell line	Male
CVCL_9T99	HeLa ICRP Bcl-2-mCherry	Cancer cell line	Female
CVCL_9U45	RC	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.