BCL2L11

Summary

BCL2L11 (BCL2 like 11, HGNC:994) is a protein-coding gene on chromosome 2q13, encoding Bcl-2-like protein 11 (O43521). Induces apoptosis and anoikis. In precision oncology, BCL2L11 Deletion Polymorphism confers sensitivity to Imatinib in Chronic Myeloid Leukemia (CIViC Level B); 2 further curated variant–drug associations are listed below.

The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified.

Source: NCBI Gene 10018 — RefSeq curated summary.

At a glance

• GWAS associations: 75
• Clinical variants (ClinVar): 53 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_138621

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:994
Approved symbol	BCL2L11
Name	BCL2 like 11
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	BOD, BimL, BimEL, BimS, BIM
Ensembl gene	ENSG00000153094
Ensembl biotype	protein_coding
OMIM	603827
Entrez	10018

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 nonsense_mediated_decay, 7 protein_coding

ENST00000308659, ENST00000361493, ENST00000393252, ENST00000393256, ENST00000405953, ENST00000415458, ENST00000431217, ENST00000432179, ENST00000433098, ENST00000436733, ENST00000437029, ENST00000438054, ENST00000439718, ENST00000452231, ENST00000715206

RefSeq mRNA: 18 — MANE Select: NM_138621 NM_001204106, NM_001204107, NM_001204108, NM_001204109, NM_001204110, NM_001204111, NM_001204112, NM_001204113, NM_006538, NM_138621, NM_138622, NM_138623, NM_138624, NM_138625, NM_138626, NM_138627, NM_207002, NM_207003

CCDS: CCDS2089, CCDS2092, CCDS42731, CCDS56131, CCDS56132, CCDS56133, CCDS56134, CCDS56135, CCDS56136, CCDS74559

Canonical transcript exons

ENST00000393256 — 4 exons

Exon	Start	End
ENSE00001008808	111123733	111124139
ENSE00001924953	111164133	111168444
ENSE00003483971	111150044	111150147
ENSE00004011574	111120914	111121188

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6248 / max 438.1583, expressed in 1717 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21946	23.6021	1680
21949	0.9214	561
21947	0.5713	301
21948	0.5300	312

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.66	gold quality
palpebral conjunctiva	UBERON:0001812	94.36	gold quality
male germ cell	CL:0000015	92.27	gold quality
epithelium of nasopharynx	UBERON:0001951	91.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.85	gold quality
superficial temporal artery	UBERON:0001614	91.28	gold quality
gingival epithelium	UBERON:0001949	90.77	gold quality
monocyte	CL:0000576	89.63	gold quality
mononuclear cell	CL:0000842	89.27	gold quality
leukocyte	CL:0000738	89.26	gold quality
colonic mucosa	UBERON:0000317	89.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.47	gold quality
jejunal mucosa	UBERON:0000399	88.45	gold quality
gingiva	UBERON:0001828	88.41	gold quality
trabecular bone tissue	UBERON:0002483	88.28	gold quality
mammary duct	UBERON:0001765	88.04	gold quality
cartilage tissue	UBERON:0002418	88.01	gold quality
buccal mucosa cell	CL:0002336	87.87	gold quality
sural nerve	UBERON:0015488	87.47	gold quality
blood	UBERON:0000178	87.38	gold quality
germinal epithelium of ovary	UBERON:0001304	87.22	gold quality
esophagus squamous epithelium	UBERON:0006920	86.27	gold quality
lymph node	UBERON:0000029	85.80	gold quality
right testis	UBERON:0004534	85.77	gold quality
left testis	UBERON:0004533	85.72	gold quality
granulocyte	CL:0000094	85.54	gold quality
left lobe of thyroid gland	UBERON:0001120	84.61	gold quality
thyroid gland	UBERON:0002046	84.60	gold quality
mammary gland	UBERON:0001911	84.54	gold quality
thoracic mammary gland	UBERON:0005200	84.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	47.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPD, CREB1, DDIT3, DNMT1, E2F1, EGR1, EZH2, FLT3, FOS, FOXC1, FOXO1, FOXO3, FOXO4, GATA4, JUN, MYB, MYC, NFE2L2, NFKB1, RELA, RPS3, RUNX3, SMAD4, SMAD7, SPI1, STAT5A, TP53, TSC22D3, YY1, ZBTB7A

miRNA regulators (miRDB)

186 targeting BCL2L11, 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-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
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-4534	99.99	66.58	1907
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Functional study of the mouse homolog (PMID:11859372)
• Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. (PMID:11997495)
• direct addition of BimL to mitochondria does not lead to cytochrome c release (PMID:12095614)
• Bim has an ability to activate directly the voltage-dependent anion channel, which plays an important role in apoptosis of mammalian cells. (PMID:12118373)
• BimEL activate Bax by damaging the mitochondrial membrane structure directly, in addition to its binding and antagonizing Bcl-2/Bcl-XL function. (PMID:12198137)
• BIM has a role in facilitating HIV-1 tat-induced apoptosis (PMID:12486001)
• Data show that detachment-induced expression of Bim requires a lack of beta(1)-integrin engagement, downregulation of EGF receptor (EGFR) expression and inhibition of Erk signalling. (PMID:12844146)
• Bim mRNA and protein levels increase after up-regulation of FoxO3a by paclitaxel, causing apoptosis in breast cancer cells (PMID:14527951)
• phosphorylation of Bim-EL by Erk1/2 on serine 69 selectively leads to its proteasomal degradation and therefore represents a new and important mechanism of Bim regulation (PMID:14555991)
• The proapoptotic effect of BIM (through transcriptional induction of two of its isoforms)is inhibited by the activation of Raf/ERK signalling which prevents BIM up-regulation and leads to phosphorylation of the BimEL isoform. (PMID:14676826)
• new insights into the post-translational regulation of Bim(EL) (PMID:14681225)
• Bim(EL) can be activated downstream of the caspase cascade, leading to a positive feedback amplification of apoptotic signals. (PMID:14732682)
• A new pathway for Bim regulation is based on extracellular signal-regulated kinase-dependent phosphorylation of the BimEL isoform and proteasome-ddependent degradation of BimEL, followed by increased expression of shorter apoptotic isoforms BimL and BimS. (PMID:14764673)
• Immunosuppressive agents block Bim up-regulation and rescue T cells from death receptor-independent cell death. (PMID:14970329)
• Bim appears to be a key event in cAMP-promoted apoptosis in both murine and human T-cell lymphoma and leukemia cells and thus appears to be a convergence point for the killing of such cells by glucocorticoids and agents that elevate cAMP. (PMID:14996839)
• Mcl-1L degradation by either GrB or caspase-3 interferes with Bim sequestration by Mcl-1L (PMID:15014070)
• Lovastatin-induced cell death occurs in correlation with significantly increased levels of the BH3-only protein, Bim in susceptible glioblastoma cell lines; up-regulation of Bim was directly associated with increased incidence of apoptosis (PMID:15030401)
• expression pattern of Bim isoforms shows tissue specificity; the BH3 domain is sufficiency for proapoptotic activity; the functional state of Bims might be regulated both in the transcript and post transcript process (PMID:15147734)
• Cleavage of Mcl-1 by caspases modifies its subcellular localization, increases its association with Bim and inhibits its antiapoptotic function. (PMID:15378010)
• In myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore prevents apoptosis. (PMID:15459900)
• BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors (PMID:15486195)
• the induction of Bim by GC is a required event for the complete apoptotic response in pre-B ALL cells (PMID:15509554)
• T cell blasts surviving activation-induced cell deathare memory CD44 high cells with increased BIM expression. (PMID:15653751)
• activation of transcription is activated by FoxO3A (PMID:15688014)
• Bim is a critical molecular link between the microtubule poison, paclitaxel, and apoptosis. (PMID:15711598)
• The region unique to BimEL (amino acids 41-97, exon 3) accounts for ERK1/2 binding, ERK1/2-dependent phosphorylation, and turnover of BimEL. (PMID:15728578)
• degraded during Chlamydia trachomatis infection (PMID:15731037)
• degraded in Chlamydia trachomatis-infected cells (PMID:15731089)
• Bik and Bim have roles in bortezomib sensitization of cells to killing by death receptor ligand TRAIL (PMID:15767553)
• results show that Forkhead transcription factor 4-dependent expression of Bim protein plays a pivotal role for endothelial progenitor cell apoptosis (PMID:15824087)
• expression of Bim is increased by zinc pyrithione, which induces apoptosis (PMID:15843898)
• Bim is a critical regulator of luminal apoptosis during mammary acinar morphogenesis in vitro and may be an important target of oncogenes that disrupt glandular epithelial architecture. (PMID:15899862)
• identified the transcriptional initiation site and three candidate remote enhancer/silencer regions of the Bim gene. However, none of these transcriptional regulatory elements was IL-3-dependent (PMID:16022280)
• Repression of BIM is favored in human glioblastoma. (PMID:16051596)
• Melphalan-induced apoptosis in multiple myeloma cells is associated with a cleavage of MCL1 and BIM and a decrease in the MCL1/BIM complex. (PMID:16091744)
• Bax, Bad, and Bim are upregulated, while Bcl-2 is downregulated in human neuroblastoma cells treated with propargylamine (PMID:16148027)
• The muscarinic receptor-protein kinase C signaling pathway is a regulator of Bim in neuroblastoma cells; activation of muscarinic receptors and protein kinase C o induces Bim phosphorylation, followed by down-regulation of this proapoptotic protein. (PMID:16183168)
• TGF-beta is involved in the physiological loss of gastric epithelial cells by activating apoptosis mediated by Smad7, Bim, and caspase-9 (PMID:16260615)
• Ser(87) of Bim(EL) is an important regulatory site that is targeted by Akt to attenuate the pro-apoptotic function of Bim(EL), thereby promoting cell survival (PMID:16282323)
• RUNX3 cooperates with FoxO3a/FKHRL1 to participate in the induction of apoptosis by activating Bim (PMID:16373335)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcl2l11	ENSDARG00000079144
mus_musculus	Bcl2l11	ENSMUSG00000027381
rattus_norvegicus	Bcl2l11	ENSRNOG00000016551

Paralogs (2): SCIMP (ENSG00000161929), MEI1 (ENSG00000167077)

Protein

Protein identifiers

Bcl-2-like protein 11 — O43521 (reviewed: O43521)

Alternative names: Bcl2-interacting mediator of cell death

All UniProt accessions (6): O43521, A0A0C4DH20, A0AA75IMJ6, C9J417, E9PAM9, H7BZE5

UniProt curated annotations — full annotation on UniProt →

Function. Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.

Subunit / interactions. Forms heterodimers with a number of antiapoptotic Bcl-2 proteins, including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1, BHRF1, and BCL2L2/BCLW. Does not heterodimerize with proapoptotic proteins such as BAD, BOK or BAK. Identified in a complex containing BCL2L11, DYNLL1 and BCL2L1 isoform Bcl-X(L); BH3 integrity is required for BCL2L1-binding. Interacts with YWHAZ. When phosphorylated, interacts with TRIM2; this interaction is associated with ubiquitination and degradation. Interacts with MCL1; may sequester BCL2L11 to prevent its pro-apoptotic activity. Interacts with GIMAP5. Interacts with BCL2L10/BCL-B. Interacts (when phosphorylated) with USP27X; the interaction leads to BCL2L11 deubiquitination and stabilization. Interacts with humanin; the interaction prevents BIM-induced apoptosis. Does not interact with humanin. Interacts with BAX; the interaction may lead to BAX activation through conformational change. Does not interact with humanin. Interacts with BAX; the interaction may lead to BAX activation through conformational change.

Subcellular location. Endomembrane system Mitochondrion Mitochondrion Mitochondrion Mitochondrion.

Tissue specificity. Isoform BimEL, isoform BimL and isoform BimS are the predominant isoforms and are widely expressed with tissue-specific variation. Isoform Bim-gamma is most abundantly expressed in small intestine and colon, and in lower levels in spleen, prostate, testis, heart, liver and kidney.

Post-translational modifications. Phosphorylation at Ser-69 by MAPK1/MAPK3 leads to interaction with TRIM2 and polyubiquitination, followed by proteasomal degradation. Deubiquitination catalyzed by USP27X stabilizes the protein. Ubiquitination by TRIM2 following phosphorylation by MAPK1/MAPK3 leads to proteasomal degradation. Conversely, deubiquitination catalyzed by USP27X stabilizes the protein.

Domain organisation. The BH3 motif is required for interaction with Bcl-2 proteins and cytotoxicity.

Induction. By ER stress in a DDIT3/CHOP-dependent manner.

Similarity. Belongs to the Bcl-2 family.

Isoforms (20)

UniProt ID	Names	Canonical?
O43521-1	BimEL, Bim(EL)	yes
O43521-2	BimL, Bim(L)
O43521-3	BimS, BCL2-like 11 transcript variant 9, Bim(S)
O43521-4	Bim-alpha1, BimABCD, Bim-ABCD
O43521-5	Bim-alpha2, BimACD, Bim-ACD
O43521-6	Bim-alpha3, BCL2-like 11 transcript variant 10, BimAD, Bim-AD
O43521-7	Bim-alpha4
O43521-8	Bim-alpha5
O43521-9	Bim-alpha6
O43521-10	Bim-beta1
O43521-11	Bim-beta2
O43521-12	Bim-beta3
O43521-13	Bim-beta4
O43521-14	Bim-beta5
O43521-15	Bim-beta6
O43521-16	Bim-beta7
O43521-17	Bim-gamma
O43521-18	BimABC, Bim-ABC
O43521-19	BimAC, Bim-AC
O43521-20	BimA, Bim-A

RefSeq proteins (18): NP_001191035, NP_001191036, NP_001191037, NP_001191038, NP_001191039, NP_001191040, NP_001191041, NP_001191042, NP_006529, NP_619527, NP_619528, NP_619529, NP_619530, NP_619531, NP_619532, NP_619533, NP_996885, NP_996886 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014771	Apoptosis_Bim_N	Domain
IPR015040	Bcl-x_interacting_BH3_dom	Domain
IPR017288	Bcl-2-like_11	Family
IPR052133	Immune_Signaling-Apoptosis_Reg	Family

Pfam: PF06773, PF08945

UniProt features (29 total): splice variant 16, modified residue 4, mutagenesis site 3, chain 1, region of interest 1, short sequence motif 1, sequence conflict 1, strand 1, helix 1

Structure

Experimental structures (PDB)

45 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6X8O	X-RAY DIFFRACTION	1.31
2WH6	X-RAY DIFFRACTION	1.5
4QVF	X-RAY DIFFRACTION	1.53
4A1U	X-RAY DIFFRACTION	1.54
2NL9	X-RAY DIFFRACTION	1.55
6UA3	X-RAY DIFFRACTION	1.55
5VWY	X-RAY DIFFRACTION	1.55
5VX0	X-RAY DIFFRACTION	1.6
5VWZ	X-RAY DIFFRACTION	1.62
3KJ0	X-RAY DIFFRACTION	1.7
3FDL	X-RAY DIFFRACTION	1.78
4ZIE	X-RAY DIFFRACTION	1.8
2YQ6	X-RAY DIFFRACTION	1.8
5VX2	X-RAY DIFFRACTION	1.85
5VWV	X-RAY DIFFRACTION	1.9
4B4S	X-RAY DIFFRACTION	1.9
2YQ7	X-RAY DIFFRACTION	1.9
3KJ1	X-RAY DIFFRACTION	1.95
5VX3	X-RAY DIFFRACTION	1.95
6VBX	X-RAY DIFFRACTION	1.95
3D7V	X-RAY DIFFRACTION	2.03
4D2M	X-RAY DIFFRACTION	2.1
4YJ4	X-RAY DIFFRACTION	2.1
6UAB	X-RAY DIFFRACTION	2.1
2VM6	X-RAY DIFFRACTION	2.2
5AGX	X-RAY DIFFRACTION	2.24
3IO8	X-RAY DIFFRACTION	2.3
3KJ2	X-RAY DIFFRACTION	2.35
3IO9	X-RAY DIFFRACTION	2.4
6QFI	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43521-F1	61.15	0.07

Functional residue map

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

Post-translational modifications (4): 69, 77, 87, 94

Mutagenesis-validated functional residues (3):

Position	Phenotype
156	retains the ability to induce apoptosis. abolishes interaction with bax; in isoform bim-alpha3 and isoform bims. no effe
156	abolishes induction of apoptosis. abolishes interaction with bax and bcl2; in isoform bim-alpha3 and isoform bims. loses
160	retains the ability to induce apoptosis. abolishes interaction with bcl2; in isoform bim-alpha3 and isoform bims. no eff

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-111446	Activation of BIM and translocation to mitochondria
R-HSA-111453	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-HSA-193648	NRAGE signals death through JNK
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-8952158	RUNX3 regulates BCL2L11 (BIM) transcription
R-HSA-9607240	FLT3 Signaling
R-HSA-9614657	FOXO-mediated transcription of cell death genes
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-114452	Activation of BH3-only proteins
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-212436	Generic Transcription Pathway
R-HSA-5357801	Programmed Cell Death
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6802957	Oncogenic MAPK signaling
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-73887	Death Receptor Signaling
R-HSA-74160	Gene expression (Transcription)
R-HSA-8863678	Neurodegenerative Diseases
R-HSA-8878159	Transcriptional regulation by RUNX3
R-HSA-9614085	FOXO-mediated transcription
R-HSA-9645723	Diseases of programmed cell death
R-HSA-9734009	Defective Intrinsic Pathway for Apoptosis

MSigDB gene sets: 586 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_B_CELL_HOMEOSTASIS, GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, GOBP_MYELOID_CELL_HOMEOSTASIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, PEREZ_TP63_TARGETS, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOBP_T_CELL_HOMEOSTASIS

GO Biological Process (43): in utero embryonic development (GO:0001701), B cell homeostasis (GO:0001782), kidney development (GO:0001822), myeloid cell homeostasis (GO:0002262), apoptotic process (GO:0006915), meiosis I (GO:0007127), cell-matrix adhesion (GO:0007160), spermatogenesis (GO:0007283), male gonad development (GO:0008584), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), post-embryonic development (GO:0009791), mammary gland development (GO:0030879), positive regulation of protein-containing complex assembly (GO:0031334), response to endoplasmic reticulum stress (GO:0034976), tube formation (GO:0035148), odontogenesis of dentin-containing tooth (GO:0042475), regulation of apoptotic process (GO:0042981), T cell homeostasis (GO:0043029), positive regulation of apoptotic process (GO:0043065), positive regulation of neuron apoptotic process (GO:0043525), ear development (GO:0043583), positive regulation of cell cycle (GO:0045787), regulation of organ growth (GO:0046620), developmental pigmentation (GO:0048066), regulation of developmental pigmentation (GO:0048070), spleen development (GO:0048536), thymus development (GO:0048538), positive regulation of T cell apoptotic process (GO:0070234), thymocyte apoptotic process (GO:0070242), cellular response to glucocorticoid stimulus (GO:0071385), positive regulation of release of cytochrome c from mitochondria (GO:0090200), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), positive regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902110), positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902237), apoptotic process involved in embryonic digit morphogenesis (GO:1902263), positive regulation of IRE1-mediated unfolded protein response (GO:1903896), positive regulation of fibroblast apoptotic process (GO:2000271), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), leukocyte homeostasis (GO:0001776), lymphocyte homeostasis (GO:0002260)

GO Molecular Function (3): microtubule binding (GO:0008017), protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (10): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), endomembrane system (GO:0012505), Bcl-2 family protein complex (GO:0097136), BIM-BCL-xl complex (GO:0097140), BIM-BCL-2 complex (GO:0097141), cytoplasm (GO:0005737), microtubule (GO:0005874), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Intrinsic Pathway for Apoptosis	2
Activation of BH3-only proteins	1
Cell death signalling via NRAGE, NRIF and NADE	1
Oncogenic MAPK signaling	1
Neurodegenerative Diseases	1
Transcriptional regulation by RUNX3	1
Cytokine Signaling in Immune system	1
FOXO-mediated transcription	1
Programmed Cell Death	1
Apoptosis	1
Immune System	1
Death Receptor Signaling	1
p75 NTR receptor-mediated signalling	1
RNA Polymerase II Transcription	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
lymphocyte homeostasis	2
apoptotic process	2
cytoplasm	2
Bcl-2 family protein complex	2
chordate embryonic development	1
animal organ development	1
renal system development	1
immune system process	1
homeostasis of number of cells	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
meiotic telophase I	1
meiosis I cell cycle process	1
meiotic nuclear division	1
cell-substrate adhesion	1
developmental process involved in reproduction	1
male gamete generation	1
gonad development	1
development of primary male sexual characteristics	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
multicellular organism development	1
multicellular organismal process	1
gland development	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
cellular response to stress	1
tube morphogenesis	1
anatomical structure formation involved in morphogenesis	1
odontogenesis	1
regulation of programmed cell death	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1

Protein interactions and networks

STRING

3148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCL2L11	MCL1	Q07820	999
BCL2L11	BCL2L1	Q07817	999
BCL2L11	BCL2	P10415	999
BCL2L11	BCL2L2-PABPN1	Q92843	998
BCL2L11	BECN1	Q14457	987
BCL2L11	BCL2A1	Q16548	985
BCL2L11	DYNLL1	P63167	965
BCL2L11	PMAIP1	Q13794	948
BCL2L11	CYCS	P00001	899
BCL2L11	BMF	Q96LC9	894
BCL2L11	BIK	Q13323	893
BCL2L11	BCL2L10	Q9HD36	888
BCL2L11	APAF1	O14727	887
BCL2L11	RTL10	Q7L3V2	877
BCL2L11	TP53	P04637	861

IntAct

162 interactions, top by confidence:

A	B	Type	Score
BCL2L11	MCL1	psi-mi:“MI:0407”(direct interaction)	0.950
MCL1	BCL2L11	psi-mi:“MI:0915”(physical association)	0.950
BCL2L11	MCL1	psi-mi:“MI:0915”(physical association)	0.950
MCL1	BCL2L11	psi-mi:“MI:0914”(association)	0.950
BCL2L11	BAX	psi-mi:“MI:0915”(physical association)	0.940
BCL2L11	BAX	psi-mi:“MI:0407”(direct interaction)	0.940
BAX	BCL2L11	psi-mi:“MI:0407”(direct interaction)	0.940
BAX	BCL2L11	psi-mi:“MI:2364”(proximity)	0.940
BAX	BCL2L11	psi-mi:“MI:0915”(physical association)	0.940
BAX	BCL2L11	psi-mi:“MI:0914”(association)	0.940
BCL2L11	BCL2	psi-mi:“MI:0407”(direct interaction)	0.930
BCL2L11	BCL2L2	psi-mi:“MI:0407”(direct interaction)	0.930

BioGRID (209): BCL2L11 (Protein-peptide), BCL2L11 (Protein-peptide), BCL2L11 (Affinity Capture-MS), BCL2L11 (Two-hybrid), BCL2L1 (Affinity Capture-Western), BCL2L11 (Affinity Capture-Western), BCL2L11 (Affinity Capture-Western), BCL2L11 (Protein-peptide), BCL2L11 (Protein-peptide), BCL2L11 (Protein-peptide), BCL2L11 (Protein-peptide), BCL2L11 (Protein-peptide), BCL2L11 (Affinity Capture-Western), F1L (Affinity Capture-Western), BCL2L11 (Affinity Capture-Western)

ESM2 similar proteins: A0A088MLT8, A6NNE9, A6P320, B3KU38, B5DF41, D4AE48, G3V9M2, O15079, O43521, O54918, O75081, O88498, P0C1G7, P0DPB3, P0DPB4, P49796, P53349, P78524, Q14DQ1, Q1LY51, Q3U3E2, Q50H33, Q5FVG6, Q5XKK7, Q60698, Q62925, Q68FF7, Q6P1L5, Q6ZNC4, Q7TNF9, Q80TE3, Q80U23, Q80U62, Q80UZ0, Q86VQ1, Q8BGW2, Q8BWU3, Q8CBH7, Q8IWP9, Q8K3I9

Diamond homologs: O43521, O54918, O88498

SIGNOR signaling

52 interactions.

A	Effect	B	Mechanism
MAPK1	“down-regulates quantity by destabilization”	BCL2L11	phosphorylation
MAPK3	“down-regulates quantity by destabilization”	BCL2L11	phosphorylation
BCL2L11	“down-regulates activity”	BCL2	binding
BCL2L11	down-regulates	BCL2	binding
BCL2L11	down-regulates	BCL2L1	binding
BCL2L11	down-regulates	BCL2L2	binding
14-3-3	down-regulates	BCL2L11	binding
AKT	“down-regulates activity”	BCL2L11	phosphorylation
BCL2L11	“up-regulates activity”	BAX	binding
MAPK8	“down-regulates quantity by destabilization”	BCL2L11	phosphorylation
MAPK8	down-regulates	BCL2L11	phosphorylation
BCL2L11	“down-regulates activity”	BCL2L1	binding
MAPK10	up-regulates	BCL2L11	phosphorylation
MAPK8	up-regulates	BCL2L11	phosphorylation
BCL2L11	up-regulates	BAK1	binding
“ER stress”	up-regulates	BCL2L11
FOXO1	“up-regulates quantity by expression”	BCL2L11	“transcriptional regulation”
FOXO3	“up-regulates quantity by expression”	BCL2L11	“transcriptional regulation”
AKT1	“down-regulates activity”	BCL2L11	phosphorylation
FOXO	“up-regulates quantity by expression”	BCL2L11	“transcriptional regulation”
SMAD3/SMAD4	“up-regulates quantity by expression”	BCL2L11	“transcriptional regulation”
BCL2L11	up-regulates	Apoptosis
CDK1	“up-regulates activity”	BCL2L11	phosphorylation
Gbeta	“down-regulates quantity by destabilization”	BCL2L11	phosphorylation
ERK1/2	“down-regulates quantity by destabilization”	BCL2L11	phosphorylation
AURKA	“down-regulates quantity by destabilization”	BCL2L11	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
Intrinsic Pathway for Apoptosis	6	58.6×	2e-07
Programmed Cell Death	7	34.2×	2e-07
Apoptosis	6	33.6×	2e-06
Diseases of signal transduction by growth factor receptors and second messengers	6	11.4×	5e-04
Transcriptional Regulation by TP53	5	10.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
release of cytochrome c from mitochondria	9	143.6×	2e-15
extrinsic apoptotic signaling pathway in absence of ligand	8	85.1×	9e-12
intrinsic apoptotic signaling pathway in response to DNA damage	8	58.9×	1e-10
male gonad development	5	17.7×	4e-04
positive regulation of apoptotic process	12	15.5×	1e-09
negative regulation of apoptotic process	7	5.5×	5e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1223 predictions. Top by Δscore:

Variant	Effect	Δscore
2:111150036:T:TA	acceptor_gain	1.0000
2:111150143:GGAGG:G	donor_gain	1.0000
2:111150144:GAGG:G	donor_gain	1.0000
2:111150144:GAGGG:G	donor_gain	1.0000
2:111150145:A:T	donor_gain	1.0000
2:111150146:GG:G	donor_gain	1.0000
2:111150147:GG:G	donor_gain	1.0000
2:111164428:G:GT	donor_gain	1.0000
2:111150039:TGCA:T	acceptor_loss	0.9900
2:111150040:GCAGC:G	acceptor_loss	0.9900
2:111150041:CAG:C	acceptor_loss	0.9900
2:111150042:A:AG	acceptor_gain	0.9900
2:111150042:AG:A	acceptor_loss	0.9900
2:111150043:G:GG	acceptor_gain	0.9900
2:111150043:GCTT:G	acceptor_gain	0.9900
2:111150148:G:A	donor_loss	0.9900
2:111150149:T:G	donor_loss	0.9900
2:111164127:TTTCA:T	acceptor_loss	0.9900
2:111164128:TTCA:T	acceptor_loss	0.9900
2:111164129:TCAGG:T	acceptor_loss	0.9900
2:111164130:CAGG:C	acceptor_loss	0.9900
2:111164131:AGGT:A	acceptor_loss	0.9900
2:111121186:AAG:A	donor_loss	0.9800
2:111121187:AGG:A	donor_loss	0.9800
2:111121188:GGTAA:G	donor_loss	0.9800
2:111121189:GT:G	donor_loss	0.9800
2:111121190:T:G	donor_loss	0.9800
2:111122151:G:GT	donor_gain	0.9800
2:111122912:G:T	donor_gain	0.9800
2:111150043:GC:G	acceptor_gain	0.9800

AlphaMissense

1298 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:111124097:A:C	S118R	0.997
2:111124099:T:A	S118R	0.997
2:111124099:T:G	S118R	0.997
2:111150104:T:C	L152S	0.996
2:111124025:A:C	S94R	0.991
2:111124027:T:A	S94R	0.991
2:111124027:T:G	S94R	0.991
2:111150124:T:C	F159L	0.991
2:111150126:T:A	F159L	0.991
2:111150126:T:G	F159L	0.991
2:111150125:T:C	F159S	0.988
2:111150110:G:C	R154P	0.985
2:111150116:G:A	G156E	0.984
2:111124090:A:C	Q115H	0.982
2:111124090:A:T	Q115H	0.982
2:111124034:T:C	F97L	0.979
2:111124036:C:A	F97L	0.979
2:111124036:C:G	F97L	0.979
2:111150116:G:T	G156V	0.979
2:111150095:C:A	A149D	0.977
2:111124106:T:C	C121R	0.976
2:111124029:G:A	G95E	0.975
2:111150115:G:A	G156R	0.974
2:111150115:G:C	G156R	0.974
2:111124028:G:T	G95W	0.972
2:111124040:T:C	F99L	0.970
2:111124042:T:A	F99L	0.970
2:111124042:T:G	F99L	0.970
2:111150092:T:G	I148S	0.970
2:111124026:G:T	S94I	0.967

dbSNP variants (sampled 300 via entrez): RS1000051965 (2:111132891 T>A), RS1000162427 (2:111161935 T>G), RS1000266649 (2:111146536 A>G), RS1000276609 (2:111162194 G>A), RS1000391173 (2:111128916 G>A,C,T), RS1000421739 (2:111146061 G>A), RS1000491664 (2:111167785 G>A), RS1000501266 (2:111163290 G>A,C), RS1000615514 (2:111163522 A>G), RS1000655174 (2:111159690 T>C), RS1000720896 (2:111123237 C>T), RS1000776417 (2:111129941 A>G), RS1000786270 (2:111135859 A>G), RS1000807356 (2:111151505 T>G), RS1000846853 (2:111135623 T>C,G)

Disease associations

OMIM: gene MIM:603827 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

75 associations (top):

Study	Trait	p-value
GCST000224_2	Chronic lymphocytic leukemia	2.000000e-10
GCST000915_2	Primary sclerosing cholangitis	4.000000e-08
GCST001038_7	Dehydroepiandrosterone sulphate levels	2.000000e-08
GCST002073_9	Chronic lymphocytic leukemia	2.000000e-18
GCST002299_7	Chronic lymphocytic leukemia	5.000000e-15
GCST003468_23	Chronic lymphocytic leukemia	1.000000e-11
GCST004030_12	Primary sclerosing cholangitis	2.000000e-11
GCST004099_1	B-cell malignancies (chronic lymphocytic leukemia, Hodgkin lymphoma or multiple myeloma) (pleiotropy)	3.000000e-14
GCST004146_2	Chronic lymphocytic leukemia	2.000000e-27
GCST004600_75	Eosinophil percentage of white cells	1.000000e-30
GCST004606_64	Eosinophil count	1.000000e-26
GCST004608_58	Granulocyte percentage of myeloid white cells	1.000000e-12
GCST004608_59	Granulocyte percentage of myeloid white cells	6.000000e-13
GCST004609_144	Monocyte percentage of white cells	2.000000e-12
GCST004609_145	Monocyte percentage of white cells	2.000000e-21
GCST004611_15	High light scatter reticulocyte count	7.000000e-12
GCST004612_171	High light scatter reticulocyte percentage of red cells	1.000000e-13
GCST004617_68	Eosinophil percentage of granulocytes	9.000000e-32
GCST004619_163	Reticulocyte fraction of red cells	2.000000e-11
GCST004623_162	Neutrophil percentage of granulocytes	6.000000e-31
GCST004624_71	Sum eosinophil basophil counts	3.000000e-24
GCST004625_52	Monocyte count	2.000000e-11
GCST004628_148	Immature fraction of reticulocytes	1.000000e-10
GCST004633_105	Neutrophil percentage of white cells	3.000000e-10
GCST004785_28	Vitiligo	4.000000e-09
GCST004866_18	Alopecia areata	2.000000e-08
GCST004866_4	Alopecia areata	9.000000e-06
GCST004894_40	Type 2 diabetes	9.000000e-09
GCST004894_97	Type 2 diabetes	1.000000e-06
GCST004988_440	Breast cancer	4.000000e-08

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0009270	heel bone mineral density
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004587	lymphocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL3430887 (PROTEIN-PROTEIN INTERACTION), CHEMBL3883287 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885524 (PROTEIN COMPLEX), CHEMBL5169264 (PROTEIN-PROTEIN INTERACTION), CHEMBL5777 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 9,079 (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
CHEMBL443684	NAVITOCLAX	3	4,791
CHEMBL376408	ABT 737	1	4,288

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
BCL2L11 Deletion Polymorphism	Imatinib	Chronic Myeloid Leukemia	Sensitivity/Response	CIViC B	EID9701
BCL2L11 Deletion Polymorphism	Imatinib	Chronic Myeloid Leukemia	Resistance	CIViC B	EID1280
BCL2L11 Deletion Polymorphism	Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor	Lung Non-small Cell Carcinoma	Resistance	CIViC B	EID1281

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2241843	Toxicity	3	corticosteroids	Acute lymphoblastic leukemia
rs724710	Efficacy	3	imatinib	Neoplasms
rs724710	Toxicity	3	corticosteroids	Acute lymphoblastic leukemia

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs724710	BCL2L11	3	3.00	2	corticosteroids;imatinib
rs2241843	BCL2L11	3	3.25	1	corticosteroids
rs2241842	BCL2L11		0.00	0
rs73954926	ACOXL, BCL2L11		0.00	0
rs72836346	ACOXL, BCL2L11		0.00	0
rs7582030	ACOXL, BCL2L11		0.00	0
rs72836345	ACOXL, BCL2L11		0.00	0
rs6750142	BCL2L11		0.00	0
rs12613243	BCL2L11		0.00	0

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(3’R,4S,6’R,7’S,8’E,11’S)-7-chloro-7’-methoxy-11’-methyl-13’,15’-dioxospiro[2,3-dihydro-1H-naphthalene-4,22’-20-oxa-13lambda6-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,13,16(25),17,19(24)-pentaene]-13’-yl]-1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-2-carboxamide	IC50	0.135 nM	US-10703733: MCL-1 inhibitors
(R)-N-((4-(((1,4-dioxan-2-yl)methyl)amino)-3- nitrophenyl)sulfonyl)-2-((1H-pyrrolo[2,3-b] pyridin-5-yl)oxy)-4-(4-((6-(4- chlorophenyl)spiro[3.5]non-6-en-7- yl)methyl)piperazin-1-yl)benzamide	IC50	1.3 nM	US-10829488: N-(phenylsulfonyl)benzamides and related compounds as bcl-2 inhibitors
(R)-N-((4-(((1,4-dioxan-2-yl)methyl)amino)-3- nitrophenyl)sulfonyl)-2-((1H-pyrrolo[2,3-b] pyridin-5-yl)oxy)-4-(1-((6-(4- chlorophenyl)spiro[3.5]non-6-en-7-yl)methyl)- 1,2,3,6-tetrahydropyridin-4-yl)benzamide	IC50	1.4 nM	US-10829488: N-(phenylsulfonyl)benzamides and related compounds as bcl-2 inhibitors
(R)-N-((4-(((1,4-dioxan-2-yl)methyl)amino)-3- nitrophenyl)sulfonyl)-2-((1H-pyrrolo[2,3-b] pyridin-5-yl)oxy)-4-(1-((6-(4-chlorophenyl)-2- oxaspiro[3.5]non-6-en-7-yl)methyl)-1,2,3,6- tetrahydropyridin-4-yl)benzamide	IC50	2.1 nM	US-10829488: N-(phenylsulfonyl)benzamides and related compounds as bcl-2 inhibitors
(R)-N-((4-(((1,4-dioxan-2-yl)methyl)amino)-3- nitrophenyl)sulfonyl)-2-((1H-pyrrolo[2,3-b] pyridin-5-yl)oxy)-4-(4-((6-(4-chlorophenyl)-2- oxaspiro[3.5]non-6-en-7-yl)methyl)piperazin-1- yl)benzamide	IC50	2.4 nM	US-10829488: N-(phenylsulfonyl)benzamides and related compounds as bcl-2 inhibitors

ChEMBL bioactivities

2985 potent at pChembl≥5 of 3014 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.96	IC50	0.011	nM	CHEMBL5885338
10.85	Ki	0.014	nM	CHEMBL5949336
10.80	IC50	0.016	nM	CHEMBL5891096
10.80	IC50	0.016	nM	CHEMBL5907521
10.80	IC50	0.016	nM	CHEMBL6022456
10.74	IC50	0.018	nM	CHEMBL5849267
10.74	IC50	0.018	nM	CHEMBL6014845
10.74	IC50	0.018	nM	CHEMBL5924042
10.72	IC50	0.019	nM	CHEMBL5950527
10.72	IC50	0.019	nM	CHEMBL6045884
10.70	IC50	0.02	nM	CHEMBL5749525
10.70	IC50	0.02	nM	CHEMBL5852367
10.68	Ki	0.021	nM	CHEMBL5890121
10.66	IC50	0.022	nM	CHEMBL5817494
10.62	IC50	0.024	nM	CHEMBL5878551
10.62	IC50	0.024	nM	CHEMBL5968615
10.60	IC50	0.025	nM	CHEMBL5778497
10.59	IC50	0.026	nM	CHEMBL5906689
10.59	IC50	0.026	nM	CHEMBL6036150
10.59	IC50	0.026	nM	CHEMBL6059897
10.59	IC50	0.026	nM	CHEMBL5833703
10.59	IC50	0.026	nM	CHEMBL5956576
10.59	IC50	0.026	nM	CHEMBL5984651
10.57	IC50	0.027	nM	CHEMBL5844734
10.57	IC50	0.027	nM	CHEMBL5925669
10.57	IC50	0.027	nM	CHEMBL5754698
10.55	IC50	0.028	nM	CHEMBL5878241
10.54	IC50	0.029	nM	CHEMBL5206723
10.54	IC50	0.029	nM	CHEMBL5897155
10.54	IC50	0.029	nM	CHEMBL5891283
10.54	IC50	0.029	nM	CHEMBL5787095
10.54	IC50	0.029	nM	CHEMBL6051099
10.54	IC50	0.029	nM	CHEMBL5930389
10.54	IC50	0.029	nM	CHEMBL5968716
10.54	IC50	0.029	nM	CHEMBL6021982
10.52	IC50	0.03	nM	CHEMBL6047991
10.52	IC50	0.03	nM	CHEMBL5816998
10.52	IC50	0.03	nM	CHEMBL5933881
10.52	IC50	0.03	nM	CHEMBL5842251
10.52	IC50	0.03	nM	CHEMBL6026670
10.52	IC50	0.03	nM	CHEMBL5915196
10.52	IC50	0.03	nM	CHEMBL5785976
10.52	IC50	0.03	nM	CHEMBL5910112
10.52	IC50	0.03	nM	CHEMBL5852367
10.51	IC50	0.031	nM	CHEMBL5967418
10.51	IC50	0.031	nM	CHEMBL6043156
10.51	IC50	0.031	nM	CHEMBL5788209
10.51	IC50	0.031	nM	CHEMBL5868178
10.51	IC50	0.031	nM	CHEMBL5758969
10.51	IC50	0.031	nM	CHEMBL5884415

PubChem BioAssay actives

134 with measured affinity, of 202 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’R,4S,6’R,7’S,8’E,11’S)-7-chloro-7’-methoxy-11’-methyl-13’,15’-dioxospiro[2,3-dihydro-1H-naphthalene-4,22’-20-oxa-13lambda6-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,13,16(25),17,19(24)-pentaene]-13’-yl]-1-methyl-5-[[4-(oxetan-3-yl)piperazin-1-yl]methyl]pyrrole-3-carboxamide	1845337: Inhibition of C-terminal His6-tagged recombinant human MCL-1 (171 to 327 residues/biotinylated Bim (51 to 76 residues) interaction incubated for 1 hrs followed by Bim addition and measured after 2 hrs by AlphaLISA assay	ic50	<0.0001	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	515600: Inhibition of GST-tagged Bcl-xl/FITC-conjugated Bim interaction by fluorescence polarisation assay	ic50	0.0020	uM
(1S,5S,13R)-13-[[4-chloro-3-(2-phenylethyl)phenyl]methyl]-10-methyl-5-[(4-methylsulfonylphenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.0030	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	1189618: Inhibition of Bcl-xL/Bim (unknown origin) by ELISA	ic50	0.0043	uM
(1S,5S,13R)-13-[[4-chloro-3-(2-phenylethyl)phenyl]methyl]-5-[(4-chlorophenyl)methyl]-10-methyl-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.0450	uM
(1S,5S,13R)-13-[[4-chloro-3-(2-phenylethynyl)phenyl]methyl]-10-methyl-5-[(4-methylsulfonylphenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.0470	uM
(1S,5S,7S,13R)-5-[(4-chlorophenyl)methyl]-13-[(3,4-dichlorophenyl)methyl]-7,10-dimethyl-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.0480	uM
(1S,5S,13R)-13-[(4-chloro-3-naphthalen-2-ylphenyl)methyl]-10-methyl-5-[(4-methylsulfonylphenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.1120	uM
(1S,5S,13R)-13-[(3,4-dichlorophenyl)methyl]-10-methyl-5-[(4-methylsulfonylphenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.1160	uM
(1S,5S,13R)-13-[[3-(1-benzofuran-2-yl)-4-chlorophenyl]methyl]-10-methyl-5-[(4-methylsulfonylphenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.1160	uM
(1S,5S,14R)-5-[(4-chlorophenyl)methyl]-14-[(3,4-dichlorophenyl)methyl]-11-methyl-2,6,11,15,18-pentazatricyclo[16.8.1.019,24]heptacosa-19,21,23-triene-3,12,16,27-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.1220	uM
(3S)-3-amino-N-[(3S)-1-[2-[[(2R)-1-[4-chloro-3-(2-phenylethyl)phenyl]-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]-4-(4-methylsulfonylphenyl)butanamide	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.1330	uM
6-(4-bromophenyl)sulfanyl-2-(2,6-dioxopiperidin-3-yl)benzo[de]isoquinoline-1,3-dione	1858816: Inhibition of Mcl-1/Bim (unknown origin) by ELISA method	ic50	0.1500	uM
(1S,5S,13R)-5-[(4-chlorophenyl)methyl]-13-[(3,4-dichlorophenyl)methyl]-10-methyl-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.1550	uM
(3S)-3-amino-4-(4-chlorophenyl)-N-[(3S)-1-[2-[[(2R)-1-[4-chloro-3-(2-phenylethyl)phenyl]-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]butanamide	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.1930	uM
(1S,5S,15R)-5-[(4-chlorophenyl)methyl]-15-[(3,4-dichlorophenyl)methyl]-12-methyl-2,6,12,16,19-pentazatricyclo[17.8.1.020,25]octacosa-20,22,24-triene-3,13,17,28-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.2770	uM
methyl (2Z,5S)-5-(4-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858806: Binding affinity to Bcl-xL/Bim (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.2800	uM
ethyl (2Z,5R)-5-(3-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858806: Binding affinity to Bcl-xL/Bim (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.2900	uM
ethyl (2Z,5S)-5-(3-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858806: Binding affinity to Bcl-xL/Bim (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.3400	uM
(1S,5S,13R)-13-[[4-chloro-3-[(E)-2-phenylethenyl]phenyl]methyl]-10-methyl-5-[(4-methylsulfonylphenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.3750	uM
1-hydroxy-3-[(4-methoxyphenyl)-(4-methylpiperazin-1-yl)methyl]-2-phenylindole	1938333: Inhibition of Bfl-1/Bim (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.4000	uM
[4,5-dichloro-1-[4,5-dichloro-2-[2-hydroxy-4-(1-octyltriazol-4-yl)benzoyl]-1H-pyrrol-3-yl]pyrrol-2-yl]-[4-(1-heptyltriazol-4-yl)-2-hydroxyphenyl]methanone	1189618: Inhibition of Bcl-xL/Bim (unknown origin) by ELISA	ic50	0.5000	uM
N-[2-[6-(4-bromophenyl)sulfanyl-1,3-dioxobenzo[de]isoquinolin-2-yl]ethyl]-2-naphthalen-2-yloxyacetamide	1858816: Inhibition of Mcl-1/Bim (unknown origin) by ELISA method	ic50	0.5100	uM
(1S,5S,13R)-13-[(3,4-dichlorophenyl)methyl]-10-methyl-5-[[4-(methylsulfonimidoyl)phenyl]methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.5100	uM
8-[[7-(4-bromophenyl)sulfanyl-2-cyano-3-oxophenalen-1-yl]amino]-N-[5-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]pentyl]-6-oxooctanamide	1858817: Inhibition of Bcl-2/Bim (unknown origin) by ELISA method	ic50	0.5400	uM
methyl (2Z,5R)-5-(4-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858806: Binding affinity to Bcl-xL/Bim (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.5500	uM
4-[[(1S,5S,13R)-13-[(3,4-dichlorophenyl)methyl]-10-methyl-3,11,15,26-tetraoxo-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-trien-5-yl]methyl]benzenesulfonamide	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.5580	uM
[1-[2-(4-benzylsulfanyl-2-hydroxybenzoyl)-4,5-dichloro-1H-pyrrol-3-yl]-4,5-dichloropyrrol-2-yl]-(4-benzylsulfanyl-2-hydroxyphenyl)methanone	1189618: Inhibition of Bcl-xL/Bim (unknown origin) by ELISA	ic50	0.6000	uM
[4,5-dichloro-1-[4,5-dichloro-2-[2-hydroxy-4-[(4-methoxyphenyl)methylsulfanyl]benzoyl]-1H-pyrrol-3-yl]pyrrol-2-yl]-[2-hydroxy-4-[(4-methoxyphenyl)methylsulfanyl]phenyl]methanone	1189618: Inhibition of Bcl-xL/Bim (unknown origin) by ELISA	ic50	0.6000	uM
[4,5-dichloro-3-[3,4-dichloro-2-[2-hydroxy-4-[(4-methoxyphenyl)methylsulfanyl]benzoyl]pyrrol-1-yl]-1H-pyrrol-2-yl]-[2-hydroxy-4-[(4-methoxyphenyl)methylsulfanyl]phenyl]methanone	1858818: Inhibition of GST-tagged Bcl-xL/Bim (unknown origin) incubated for 15 mins followed by Bim addition measured after 2 hrs by ELISA method	ic50	0.6000	uM
[3-[2-(4-benzylsulfanyl-2-hydroxybenzoyl)-3,4-dichloropyrrol-1-yl]-4,5-dichloro-1H-pyrrol-2-yl]-(4-benzylsulfanyl-2-hydroxyphenyl)methanone	1858818: Inhibition of GST-tagged Bcl-xL/Bim (unknown origin) incubated for 15 mins followed by Bim addition measured after 2 hrs by ELISA method	ic50	0.6000	uM
(1S,5S,7R,13R)-5-[(4-chlorophenyl)methyl]-13-[(3,4-dichlorophenyl)methyl]-7,10-dimethyl-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.7390	uM
(1S,5S,13R)-13-[(3,4-dichlorophenyl)methyl]-10-methyl-5-[(4-methylsulfinylphenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957162: Inhibition of N-terminal GST-tagged human recombinant Mcl-1 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	0.7420	uM
[4,5-dichloro-1-[4,5-dichloro-2-[2-hydroxy-4-(1-phenyltriazol-4-yl)benzoyl]-1H-pyrrol-3-yl]pyrrol-2-yl]-[2-hydroxy-4-(1-phenyltriazol-4-yl)phenyl]methanone	1189618: Inhibition of Bcl-xL/Bim (unknown origin) by ELISA	ic50	0.8000	uM
(2Z,5R)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-N,5-diphenyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxamide	1858806: Binding affinity to Bcl-xL/Bim (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.8300	uM
[4-[4,5-dichloro-3-[2,3-dichloro-5-(2-hydroxybenzoyl)pyrrol-1-yl]-1H-pyrrole-2-carbonyl]-3-hydroxyphenyl] trifluoromethanesulfonate	1189617: Inhibition of Mcl1/Bim (unknown origin) by ELISA	ic50	1.0000	uM
(3S)-3-amino-4-(4-bromophenyl)-N-[(3S)-1-[2-[[(2R)-1-(3,4-dichlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-3-amino-4-(4-chlorophenyl)-N-[(3S)-1-[2-[[(2R)-1-(3,4-dichlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(1S,5S,13R)-5-[(4-chlorophenyl)methyl]-13-[(3,4-dichlorophenyl)methyl]-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-4-(4-chlorophenyl)-N-[(3S)-1-[2-[[(2R)-1-(3,4-dichlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]-3-(ethylamino)butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-3-amino-4-(4-chlorophenyl)-N-[(3S)-1-[2-[[(2R)-1-(3,4-dichlorophenyl)-4-(dimethylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-3-amino-N-[(3S)-1-[2-[[(2R)-1-[4-chloro-3-(4-chloro-3-methylphenyl)phenyl]-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]-4-(4-chlorophenyl)butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-3-amino-N-[(3S)-1-[2-[[(2R)-1-(3-benzyl-4-chlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]-4-(4-chlorophenyl)butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-3-amino-4-(4-chlorophenyl)-N-[(3S)-1-[2-[[(2R)-1-(4-chlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(1S,5S,13R)-13-[[3-(1-benzofuran-2-yl)-4-chlorophenyl]methyl]-5-[(4-chlorophenyl)methyl]-10-methyl-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(1S,5S,13R)-13-[[4-chloro-3-[(E)-2-phenylethenyl]phenyl]methyl]-5-[(4-chlorophenyl)methyl]-10-methyl-2,6,10,14,17-pentazatricyclo[15.8.1.018,23]hexacosa-18,20,22-triene-3,11,15,26-tetrone	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-3-amino-N-[(3S)-1-[2-[[(2R)-1-(4-chlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]-4-phenylbutanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(3S)-3-amino-4-(4-chlorophenyl)-N-[(3S)-1-[2-[[(2R)-1-(3-chlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]butanamide	1957158: Inhibition of his-tagged human recombinant Bcl-2 expressed in Escherichia coli /human Bim measured for 60 mins by by TR-FRET based LanthaScreen Eu-Kinase binding assay	ic50	1.0000	uM
(2Z,5S)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-N,5-diphenyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxamide	1858806: Binding affinity to Bcl-xL/Bim (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	1.1000	uM
ethyl 2-[4-[4,5-dichloro-1-[4,5-dichloro-2-[4-(2-ethoxy-2-oxoethyl)sulfanyl-2-hydroxybenzoyl]-1H-pyrrol-3-yl]pyrrole-2-carbonyl]-3-hydroxyphenyl]sulfanylacetate	1189618: Inhibition of Bcl-xL/Bim (unknown origin) by ELISA	ic50	1.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects binding, increases reaction, decreases phosphorylation, decreases reaction, increases degradation (+4 more)	8
Resveratrol	affects reaction, increases expression, affects cotreatment, decreases reaction, increases activity (+2 more)	7
(+)-JQ1 compound	increases expression, increases reaction, affects expression	6
Bortezomib	affects cotreatment, decreases reaction, increases expression, increases response to substance, increases degradation (+1 more)	6
Vorinostat	affects cotreatment, decreases expression, increases expression, increases reaction	5
Dexamethasone	increases response to substance, increases expression, increases phosphorylation, decreases reaction, affects cotreatment (+1 more)	5
Valproic Acid	affects reaction, increases expression, affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression, affects expression, decreases reaction, increases expression	4
romidepsin	increases expression, affects cotreatment, decreases reaction	4
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	affects cotreatment, decreases phosphorylation, increases expression, increases reaction, decreases expression (+1 more)	4
Estradiol	increases expression, affects expression	4
bisphenol A	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	3
methylselenic acid	affects cotreatment, affects response to substance, increases activity, increases cleavage, increases reaction (+2 more)	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects cotreatment, decreases phosphorylation, decreases expression, decreases reaction, increases expression (+1 more)	3
pyrazolanthrone	decreases reaction, increases degradation, increases expression	3
ABT-737	affects binding, decreases reaction, increases activity, increases reaction, affects response to substance (+2 more)	3
Sorafenib	affects cotreatment, increases expression, decreases expression, affects localization	3
Panobinostat	increases expression, increases reaction, affects cotreatment, decreases expression	3
Acetaminophen	decreases expression, increases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
Cisplatin	increases expression, decreases reaction, increases phosphorylation, increases reaction, affects cotreatment	3
Doxorubicin	affects cotreatment, affects response to substance, increases cleavage, decreases expression, increases expression (+4 more)	3
Quercetin	decreases expression, increases expression	3
Silicon Dioxide	decreases expression, decreases methylation	3
picrasidine I	increases expression	2
indole-3-carbinol	increases expression	2
ochratoxin A	decreases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
mercuric bromide	decreases expression, affects cotreatment	2

ChEMBL screening assays

38 unique, capped per target: 36 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2071733	Binding	Inhibition of GST-Mcl-1/BH3 domain of Bim interaction at 25 uM after 1 hr by ELISA	Synthesis and evaluation of substituted hexahydronaphthalenes as novel inhibitors of the Mcl-1/BimBH3 interaction. — Bioorg Med Chem Lett
CHEMBL1794562	Functional	PUBCHEM_BIOASSAY: Secondary assay of A1 inhibitors in Mouse Embryonic Fibroblasts with alternate A1 construct Measured in Cell-Based System Using Plate Reader - 2045-05_Inhibitor_Dose_DryPowder_Activity_Set2. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KW12	InCELL Hunter U2OS BCL2-BIM Protein Binding	Cancer cell line	Female
CVCL_KW14	InCELL Hunter U2OS BCL2L1-BIM Protein Binding	Cancer cell line	Female
CVCL_KW15	InCELL Hunter U2OS MCL1-BIM Protein Binding	Cancer cell line	Female

Clinical trials (associated diseases)

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