PSMB5

Summary

PSMB5 (proteasome 20S subunit beta 5, HGNC:9542) is a protein-coding gene on chromosome 14q11.2, encoding Proteasome subunit beta type-5 (P28074). Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. It is a common-essential gene (DepMap: required in 95.0% of cancer cell lines).

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic subunit 3i (proteasome beta 8 subunit). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5693 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 35 total
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 95.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_002797

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9542
Approved symbol	PSMB5
Name	proteasome 20S subunit beta 5
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MB1
Ensembl gene	ENSG00000100804
Ensembl biotype	protein_coding
OMIM	600306
Entrez	5693

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 nonsense_mediated_decay

ENST00000334454, ENST00000361611, ENST00000425762, ENST00000460922, ENST00000493471, ENST00000555895, ENST00000896864, ENST00000896865, ENST00000896866, ENST00000926152, ENST00000926153, ENST00000926154

RefSeq mRNA: 3 — MANE Select: NM_002797 NM_001130725, NM_001144932, NM_002797

CCDS: CCDS45083, CCDS45084, CCDS9584

Canonical transcript exons

ENST00000361611 — 3 exons

Exon	Start	End
ENSE00000889197	23025856	23026375
ENSE00001149729	23034684	23034900
ENSE00003535354	23033368	23033674

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 169.8429 / max 793.4199, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142293	167.3078	1824
142294	1.8065	1116
142295	0.7286	496

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.84	gold quality
islet of Langerhans	UBERON:0000006	98.67	gold quality
muscle of leg	UBERON:0001383	98.64	gold quality
stromal cell of endometrium	CL:0002255	98.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.35	gold quality
cortical plate	UBERON:0005343	98.30	gold quality
muscle organ	UBERON:0001630	98.27	gold quality
right adrenal gland	UBERON:0001233	98.26	gold quality
ganglionic eminence	UBERON:0004023	98.18	gold quality
right adrenal gland cortex	UBERON:0035827	98.13	gold quality
left adrenal gland	UBERON:0001234	98.01	gold quality
deltoid	UBERON:0001476	97.92	gold quality
embryo	UBERON:0000922	97.88	gold quality
left adrenal gland cortex	UBERON:0035825	97.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.83	gold quality
adrenal tissue	UBERON:0018303	97.79	gold quality
smooth muscle tissue	UBERON:0001135	97.78	gold quality
prefrontal cortex	UBERON:0000451	97.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.73	gold quality
apex of heart	UBERON:0002098	97.72	gold quality
ventricular zone	UBERON:0003053	97.69	gold quality
tibialis anterior	UBERON:0001385	97.64	gold quality
right atrium auricular region	UBERON:0006631	97.64	gold quality
heart left ventricle	UBERON:0002084	97.58	gold quality
adrenal cortex	UBERON:0001235	97.53	gold quality
cardiac ventricle	UBERON:0002082	97.48	gold quality
adrenal gland	UBERON:0002369	97.47	gold quality
skeletal muscle tissue	UBERON:0001134	97.46	gold quality
lower esophagus	UBERON:0013473	97.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.45	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	9.80
E-MTAB-10042	yes	8.41
E-CURD-53	no	254.26
E-GEOD-125970	no	3.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, GABPA, NFE2L2, SP1, STAT3

miRNA regulators (miRDB)

20 targeting PSMB5, 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-1184	99.99	68.19	1458
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-4669	97.94	62.71	224
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-27B-5P	97.34	66.55	549
HSA-MIR-6802-3P	97.29	65.42	613
HSA-MIR-6869-5P	97.17	67.06	634
HSA-MIR-921	97.09	66.45	562
HSA-MIR-3174	94.63	63.64	577

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 26)

• interaction of TAP1 and TAP2 and P-glycoprotein with proteasome subunits beta-5 and beta-5i suggest direct targeting of antigenic peptides to the ER via a TAP-proteasome association and a possible role for P-glycoprotein (PMID:15488952)
• Proteasome activity can be genetically “upregulated” in lens cells by overexpression of beta5 catalytic subunit. Resulting increase in proteasome activity leads to decrease in oxidized proteins and enhanced cell survival following oxidative stress. (PMID:17262013)
• G322A mutation of the PSMB5 gene is a novel mechanism for bortezomib resistance. (PMID:18502982)
• nonsynonymous coding single nucleotide polymorphismsin the proteasome beta 5 subunit gene did not show significant effects on proteasome activity, but SNPs did influence transcription (PMID:18519783)
• Overexpression of PSMB5 is an important mechanism for bortezomib resistance in Jurkat cell lines. (PMID:18562081)
• a novel mechanism of bortezomib resistance associated with the selective overexpression of a mutant PSMB5 protein (PMID:18565852)
• Nuclear MB1 expression was an independent predictor of worse survival in ovarian cancer. (PMID:19243813)
• Mutations of the PSMB5 gene resulting in substitutions of Ala49 and Ala50 of PSMB5 protein can confer varying bortezomib resistance (PMID:19426847)
• Expression of mutated PSMB5 was associated with the prevention of the accumulation of unfolded proteins (PMID:20555361)
• CDK5 regulation of proteasome subunit PSMB5 was identified as a probable route to antineoplastic drug sensitization. (PMID:21289309)
• No mutations or differences in PSMB5 mRNA expression were seen before bortezomib treatment in 3 multiple myeloma patients, but after treatment, 1 patient showed PSMB5 upregulation associated with bortezomib resistance. (PMID:21920470)
• PSMB5 overexpression is associated with Bortezomib resistance in myeloma. (PMID:21978467)
• Letter/Case Reports: proteasome subunit beta5t is expressed in cervical ectopic thymoma. (PMID:22523338)
• The expression of proteasome beta5 decreases markedly in human atherosclerotic plaques. (PMID:22781773)
• Data indicate that treatment-emergent resistance to single-agent bortezomib was independent of variants in the proteasome genes PSMB1, PSMB5, PSMB6, PSMB8, PSMB9, and PSMB10. (PMID:23018640)
• critical role of PSMB5 in 20S proteasome-mediated protection against replicative senescence, pointing to a possible strategy for maintaining the integrity of culture-expanded bone marrow stromal cells by manipulating the expression of PSMB5 (PMID:24393841)
• Data indicate that proteasomal subunit X PSMB5 is a target of signal transducer and activator of transcription 3 (STAT3). (PMID:24627483)
• Results identified PSMB5 Q62P mutation to underlie bortezomib resistance in Down-syndrome-associated acute myeloid leukemia cells. (PMID:28143565)
• We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant (PMID:28453575)
• Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for Triple-negative breast cancer (PMID:28623645)
• PSMB5 knockdown could increase the expression of pro-apoptosis gene Bax and cleaved caspase-3 (PMID:29365400)
• PSMB5 mutations are associated with multiple myeloma. (PMID:30026573)
• Transcriptional downregulation of miR-127-3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5. (PMID:31562641)
• Identification of PSMB5 as a genetic modifier of fragile X-associated tremor/ataxia syndrome. (PMID:35617426)
• PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma. (PMID:36062301)
• MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5. (PMID:38252234)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb5	ENSDARG00000075445
mus_musculus	Psmb5	ENSMUSG00000022193
rattus_norvegicus	Psmb5	ENSRNOG00000013386
drosophila_melanogaster	Prosbeta1	FBGN0010590
caenorhabditis_elegans		WBGENE00003947

Paralogs (18): PSMB1 (ENSG00000008018), PSMA4 (ENSG00000041357), PSMA3 (ENSG00000100567), PSMA6 (ENSG00000100902), PSMA7 (ENSG00000101182), PSMA2 (ENSG00000106588), PSMB2 (ENSG00000126067), PSMA1 (ENSG00000129084), PSMB7 (ENSG00000136930), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit beta type-5 — P28074 (reviewed: P28074)

Alternative names: Macropain epsilon chain, Multicatalytic endopeptidase complex epsilon chain, Proteasome chain 6, Proteasome epsilon chain, Proteasome subunit MB1, Proteasome subunit X, Proteasome subunit beta-5

All UniProt accessions (5): P28074, A0A140VJS7, G3V3K3, G8JLC2, H0YJM8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity.

Subunit / interactions. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Directly interacts with POMP. Interacts with ABCB1 and TAP1. (Microbial infection) Interacts with HIV-1 TAT protein.

Subcellular location. Cytoplasm. Nucleus.

Induction. Down-regulated by IFNG/IFN-gamma (at protein level). Induced in breast cancer tissue. Up-regulated by sulforaphane in breast cancer cells.

Similarity. Belongs to the peptidase T1B family.

Isoforms (3)

UniProt ID	Names	Canonical?
P28074-1	1	yes
P28074-2	2
P28074-3	3

RefSeq proteins (3): NP_001124197, NP_001138404, NP_002788* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000243	Pept_T1A_subB	Family
IPR001353	Proteasome_sua/b	Family
IPR016050	Proteasome_bsu_CS	Conserved_site
IPR023333	Proteasome_suB-type	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily

Pfam: PF00227

UniProt features (41 total): strand 17, helix 6, sequence conflict 5, turn 3, mutagenesis site 3, splice variant 2, propeptide 1, chain 1, active site 1, binding site 1, sequence variant 1

Structure

Experimental structures (PDB)

152 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5LE5	X-RAY DIFFRACTION	1.8
5LEY	X-RAY DIFFRACTION	1.9
5LF4	X-RAY DIFFRACTION	1.99
5LF1	X-RAY DIFFRACTION	2
5LF7	X-RAY DIFFRACTION	2
8UD9	ELECTRON MICROSCOPY	2.04
5LF6	X-RAY DIFFRACTION	2.07
5LF3	X-RAY DIFFRACTION	2.1
8BZL	X-RAY DIFFRACTION	2.14
5LEZ	X-RAY DIFFRACTION	2.19
5LEX	X-RAY DIFFRACTION	2.2
5LF0	X-RAY DIFFRACTION	2.41
9K53	ELECTRON MICROSCOPY	2.5
9HMN	ELECTRON MICROSCOPY	2.55
4R3O	X-RAY DIFFRACTION	2.6
6RGQ	ELECTRON MICROSCOPY	2.6
9YUZ	ELECTRON MICROSCOPY	2.6
5L5Y	X-RAY DIFFRACTION	2.7
5L5Z	X-RAY DIFFRACTION	2.7
5L60	X-RAY DIFFRACTION	2.7
5L63	X-RAY DIFFRACTION	2.7
5L64	X-RAY DIFFRACTION	2.7
8CVR	ELECTRON MICROSCOPY	2.7
6KWY	ELECTRON MICROSCOPY	2.72
9MBP	ELECTRON MICROSCOPY	2.75
5L5W	X-RAY DIFFRACTION	2.8
5L61	X-RAY DIFFRACTION	2.8
5L62	X-RAY DIFFRACTION	2.8
7NAN	ELECTRON MICROSCOPY	2.8
8TM6	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28074-F1	83.34	0.76

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): 60 (nucleophile)

Ligand- & substrate-binding residues (1): 108

Mutagenesis-validated functional residues (3):

Position	Phenotype
108	displays resistance to the bortezomib, a proteasome inhibitor of the chymotrypsin-like activity. displays high resistanc
108	displays high resistance to the bortezomib, a proteasome inhibitor of the chymotrypsin-like activity.
109	displays high resistance to the bortezomib, a proteasome inhibitor of the chymotrypsin-like activity; when associated wi

Function

Pathways and Gene Ontology

Reactome pathways

68 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-180534	Vpu mediated degradation of CD4
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-202424	Downstream TCR signaling
R-HSA-211733	Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-350562	Regulation of ornithine decarboxylase (ODC)
R-HSA-382556	ABC-family protein mediated transport
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-4608870	Asymmetric localization of PCP proteins
R-HSA-4641257	Degradation of AXIN
R-HSA-4641258	Degradation of DVL
R-HSA-5358346	Hedgehog ligand biogenesis
R-HSA-5362768	Hh mutants are degraded by ERAD
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5610780	Degradation of GLI1 by the proteasome
R-HSA-5610783	Degradation of GLI2 by the proteasome

MSigDB gene sets: 412 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, REACTOME_DNA_REPLICATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, REACTOME_SIGNALING_BY_NOTCH, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, PAL_PRMT5_TARGETS_UP, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION

GO Biological Process (6): proteolysis (GO:0006508), response to oxidative stress (GO:0006979), proteasomal ubiquitin-independent protein catabolic process (GO:0010499), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), proteasome assembly (GO:0043248), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (5): endopeptidase activity (GO:0004175), threonine-type endopeptidase activity (GO:0004298), peptidase activity (GO:0008233), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (11): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), proteasome core complex (GO:0005839), proteasome core complex, beta-subunit complex (GO:0019774), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
APC/C-mediated degradation of cell cycle proteins	2
Host Interactions of HIV factors	2
Downstream signaling events of B Cell Receptor (BCR)	1
Cellular response to hypoxia	1
Regulation of APC/C activators between G1/S and early anaphase	1
APC/C:Cdc20 mediated degradation of mitotic proteins	1
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Signaling by WNT	1
TCR signaling	1
Regulation of Apoptosis	1
Mitotic Anaphase	1
Fc epsilon receptor (FCERI) signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
proteasomal protein catabolic process	2
intracellular protein-containing complex	2
intracellular anatomical structure	2
sperm flagellum	2
protein metabolic process	1
response to stress	1
ubiquitin-dependent protein catabolic process	1
protein-containing complex assembly	1
peptidase activity	1
endopeptidase activity	1
threonine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
proteasome complex	1
catalytic complex	1
proteasome core complex	1
protein-containing complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

2981 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB5	PSMB7	Q99436	979
PSMB5	PSMB6	P28072	973
PSMB5	PSMB2	P31145	972
PSMB5	PSMB4	P28070	957
PSMB5	PSMB1	P20618	891
PSMB5	PSME1	Q06323	855
PSMB5	PSME2	Q9UL46	843
PSMB5	CTRL	P40313	832
PSMB5	PSMA6	P34062	803
PSMB5	PSMA1	P25786	803
PSMB5	PSMA5	P28066	796
PSMB5	PSMC3	P17980	788
PSMB5	PSMA4	P25789	781
PSMB5	PSMA3	P25788	781
PSMB5	PSMD1	Q99460	776

IntAct

246 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0915”(physical association)	0.950
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
PSMB7	PSMB1	psi-mi:“MI:0914”(association)	0.900
PSMA2	PSMA7	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMB7	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMB2	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMA2	PSMB1	psi-mi:“MI:0914”(association)	0.790
PSMB3	PSMA7	psi-mi:“MI:0914”(association)	0.770

BioGRID (522): PSMB5 (Affinity Capture-RNA), PSMB5 (Affinity Capture-RNA), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-Western), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), PSMB5 (Affinity Capture-MS), ACTN2 (Co-fractionation), ACTN4 (Co-fractionation), ASNA1 (Co-fractionation)

ESM2 similar proteins: A1XQU1, A2YXU2, A2Z3I9, A7KE01, A7KII6, O23710, O23712, O24030, O24361, O24362, O35955, O42265, O43063, O55234, P25043, P28062, P28063, P28064, P28074, P28075, P30655, P30656, P38624, P40306, P70195, P93395, Q09841, Q0J006, Q10329, Q2TBP0, Q3MHN0, Q3T0T1, Q3T112, Q4KM35, Q54BC8, Q54QR2, Q55GJ6, Q5R8S2, Q5RDH8, Q5W416

Diamond homologs: A0B5B1, A0JWY6, A0LU50, A0PQT3, A0QFB5, A0QZ47, A1KKF3, A1R6Q7, A1SK13, A1TAP4, A1UHS7, A2SS78, A3CUS9, A3Q193, A4FBY1, A4FYA5, A4TB64, A4X3P0, A4X744, A5U4D6, A5WP84, A6USJ3, A6VK02, A6W970, A7I841, A8LH54, A8M2A3, A9A788, A9WSI1, B0R4C8, B1L6S7, B1MAI2, B1W306, B2HFV6, B6YSW2, B8H8L6, B8ZRF3, B9LTS6, C0ZZU7, C1AQ26

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ixazomib	down-regulates	PSMB5	“chemical inhibition”
“ixazomib citrate”	down-regulates	PSMB5	“chemical inhibition”
carfilzomib	“down-regulates activity”	PSMB5	“chemical inhibition”
bortezomib	“down-regulates activity”	PSMB5	“chemical inhibition”
PSMB5	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 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
Antigen processing: Ub, ATP-independent proteasomal degradation	11	69.8×	6e-18
Cross-presentation of soluble exogenous antigens (endosomes)	18	50.8×	4e-25
Regulation of activated PAK-2p34 by proteasome mediated degradation	16	49.5×	1e-22
Hh mutants are degraded by ERAD	18	48.6×	9e-25
Regulation of ornithine decarboxylase (ODC)	16	48.3×	2e-22
NIK–>noncanonical NF-kB signaling	19	48.2×	1e-25
Proteasome assembly	21	47.6×	3e-28
Vpu mediated degradation of CD4	16	47.2×	2e-22

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	26	11.2×	3e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

736 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23026376:C:CC	acceptor_gain	1.0000
14:23033362:A:C	donor_gain	1.0000
14:23033481:T:TA	donor_gain	1.0000
14:23026373:GGC:G	acceptor_gain	0.9900
14:23026375:CCTG:C	acceptor_loss	0.9900
14:23026377:T:C	acceptor_loss	0.9900
14:23033363:CTC:C	donor_loss	0.9900
14:23033364:TCAC:T	donor_loss	0.9900
14:23033365:CA:C	donor_loss	0.9900
14:23033367:C:CA	donor_loss	0.9900
14:23033420:G:A	donor_gain	0.9900
14:23033428:A:AC	donor_gain	0.9900
14:23033429:C:CC	donor_gain	0.9900
14:23033430:TGA:T	donor_gain	0.9900
14:23033430:TGATA:T	donor_gain	0.9900
14:23033670:CGGAA:C	acceptor_gain	0.9900
14:23033671:GGAA:G	acceptor_gain	0.9900
14:23033672:GAA:G	acceptor_gain	0.9900
14:23033673:AA:A	acceptor_gain	0.9900
14:23033673:AACT:A	acceptor_loss	0.9900
14:23033674:AC:A	acceptor_loss	0.9900
14:23033675:C:CA	acceptor_loss	0.9900
14:23033675:C:CC	acceptor_gain	0.9900
14:23033676:T:C	acceptor_loss	0.9900
14:23033685:C:CT	acceptor_gain	0.9900
14:23033686:A:T	acceptor_gain	0.9900
14:23033360:TAAC:T	donor_loss	0.9800
14:23033381:ATC:A	donor_gain	0.9800
14:23033382:T:C	donor_gain	0.9800
14:23033431:GATAC:G	donor_gain	0.9800

AlphaMissense

1680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23026192:C:T	G230E	1.000
14:23026312:C:T	G190D	1.000
14:23026351:C:T	G177E	1.000
14:23026352:C:A	G177W	1.000
14:23026352:C:G	G177R	1.000
14:23026352:C:T	G177R	1.000
14:23033451:A:G	L141P	1.000
14:23033457:G:A	S139F	1.000
14:23033457:G:T	S139Y	1.000
14:23033460:G:T	A138D	1.000
14:23033493:A:G	L127P	1.000
14:23033507:A:C	C122W	1.000
14:23033533:A:G	W114R	1.000
14:23033533:A:T	W114R	1.000
14:23033540:G:C	C111W	1.000
14:23033541:C:T	C111Y	1.000
14:23033556:C:T	G106E	1.000
14:23026154:A:G	W243R	0.999
14:23026154:A:T	W243R	0.999
14:23026192:C:A	G230V	0.999
14:23026203:A:C	D226E	0.999
14:23026203:A:T	D226E	0.999
14:23026204:T:A	D226V	0.999
14:23026204:T:G	D226A	0.999
14:23026205:C:G	D226H	0.999
14:23026217:C:G	A222P	0.999
14:23026229:C:G	A218P	0.999
14:23026237:G:T	A215D	0.999
14:23026300:G:T	A194E	0.999
14:23026310:A:G	S191P	0.999

dbSNP variants (sampled 300 via entrez): RS1000241514 (14:23034200 G>A), RS1000394877 (14:23026598 C>G,T), RS1000456302 (14:23034468 C>G,T), RS1000494257 (14:23031031 G>A), RS1000626744 (14:23036299 A>G,T), RS1000698209 (14:23034509 C>A,G), RS1000718527 (14:23026547 T>A), RS1000728302 (14:23029039 C>T), RS1000778986 (14:23029396 C>T), RS1000977534 (14:23035967 G>A,C), RS1001176894 (14:23025631 ATC>A), RS1002408953 (14:23030613 A>C), RS1002742888 (14:23032167 G>A,T), RS1002795609 (14:23032486 A>G), RS1003044590 (14:23026622 G>T)

Disease associations

OMIM: gene MIM:600306 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004602_175	Mean corpuscular volume	3.000000e-15
GCST004611_195	High light scatter reticulocyte count	1.000000e-23
GCST004612_129	High light scatter reticulocyte percentage of red cells	3.000000e-26
GCST004619_43	Reticulocyte fraction of red cells	4.000000e-39
GCST004621_64	Red cell distribution width	2.000000e-96
GCST004622_126	Reticulocyte count	4.000000e-34
GCST004630_197	Mean corpuscular hemoglobin	1.000000e-15
GCST006804_17	Red cell distribution width	2.000000e-85
GCST90002385_19	High light scatter reticulocyte count	2.000000e-70
GCST90002386_162	High light scatter reticulocyte percentage of red cells	1.000000e-76
GCST90002387_137	Immature fraction of reticulocytes	2.000000e-22
GCST90002390_200	Mean corpuscular hemoglobin	2.000000e-45
GCST90002391_254	Mean corpuscular hemoglobin concentration	3.000000e-12
GCST90002392_420	Mean corpuscular volume	2.000000e-38
GCST90002397_70	Mean spheric corpuscular volume	3.000000e-11
GCST90002404_386	Red cell distribution width	3.000000e-243
GCST90002404_387	Red cell distribution width	1.000000e-14
GCST90002405_362	Reticulocyte count	2.000000e-72
GCST90002406_415	Reticulocyte fraction of red cells	2.000000e-84

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831201 (PROTEIN COMPLEX GROUP), CHEMBL3885625 (PROTEIN FAMILY), CHEMBL4662 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 743,741 (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
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL451887	CARFILZOMIB	4	12,508
CHEMBL159	VINBLASTINE	4	412,636
CHEMBL3545432	IXAZOMIB CITRATE	4	2,453
CHEMBL2141296	IXAZOMIB	3	6,022
CHEMBL371405	MARIZOMIB	3	7,332
CHEMBL140	CURCUMIN	3	93,882
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL50	QUERCETIN	3	74,559
CHEMBL2103884	OPROZOMIB	2	2,738
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL270515	DELANZOMIB	2	1,883
CHEMBL4297468	ZETOMIPZOMIB	2	129
CHEMBL44	GENISTEIN	2	44,212
CHEMBL150	KAEMPFEROL	1	25,940

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — T1: Proteasome

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
ixazomib	Inhibition	9.03	pKi
NIC-0102	Inhibition	8.43	pIC50
MG-132	Inhibition	8.43	pKi
compound 3b [PMID: 24946214]	Inhibition	8.29	pKi
carfilzomib	Inhibition	8.24	pIC50
oprozomib	Inhibition	8.0	pIC50
bortezomib	Inhibition	7.7	pIC50
zetomipzomib	Inhibition	6.16	pIC50
WLL-vs	Inhibition	6.0	pIC50

Binding affinities (BindingDB)

100 measured of 147 human assays (147 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL1169560	IC50	4.3 nM
CHEMBL1169561	IC50	7.6 nM
CARFILZOMIB	IC50	8.6 nM
[(1R)-1-[[2-[(3,5-dichloro-2-pyridinyl)oxy]acetyl]amino]-2-phenylethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[(2-phenoxyacetyl)amino]-2-phenylethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(4-methylphenyl)-1-(3-phenoxypropanoylamino)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[3-(4-methoxyphenoxy)propanoylamino]-2-(4-methylphenyl)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyridin-3-ylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(4-cyanophenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(4-methoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyridin-3-yloxyacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(6-methoxy-2-pyridinyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(5-ethoxy-2-pyridinyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(3-methoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyrazin-2-ylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyrimidin-2-ylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(3,4,5-trifluorophenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[[2-(4-acetamidophenyl)acetyl]amino]-2-(1-benzofuran-3-yl)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2-methoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(4-ethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[3-(3-hydroxypropoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[[2-(3-acetamidophenyl)acetyl]amino]-2-(1-benzofuran-3-yl)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(2-hydroxyethoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(3-hydroxypropoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[3-(2-hydroxyethoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[3-(methoxymethyl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(3,4,5-trimethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[2-(oxan-4-yloxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2,5-dimethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2R)-3-hydroxy-2-phenylpropanoyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2,3,4-trimethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(2-oxopyrrolidin-1-yl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(2-hydroxypropan-2-yl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(7-methoxy-1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(7-fluoro-1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-[(3S)-2,3-dihydro-1-benzofuran-3-yl]-1-(3-phenoxypropanoylamino)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
CHEMBL4563143	IC50	638 nM
CHEMBL4544082	IC50	853 nM
[(1R)-2-phenyl-1-[(2-pyridin-2-yloxyacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(4-methylphenyl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-2-(4-methylphenyl)ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyridin-4-ylacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2,2-difluoro-2-phenylacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[2-(trifluoromethyl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2,6-dichlorophenyl)acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[2-(trifluoromethoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2S)-2-methoxy-2-phenylacetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2R)-2-methoxy-2-phenylacetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(2,4-dimethylphenyl)-1-[[2-(2,6-dimethylphenyl)acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors

ChEMBL bioactivities

1663 potent at pChembl≥5 of 1872 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	CHEMBL3347481
9.89	Ki	0.13	nM	CHEMBL4749207
9.85	Ki	0.14	nM	CHEMBL3629678
9.66	IC50	0.22	nM	CHEMBL3347627
9.52	IC50	0.3	nM	CHEMBL4070336
9.47	IC50	0.34	nM	CHEMBL3347641
9.42	IC50	0.38	nM	CHEMBL3347480
9.41	IC50	0.39	nM	CHEMBL3347642
9.40	IC50	0.4	nM	CHEMBL3347625
9.38	IC50	0.42	nM	CHEMBL3347640
9.30	Ki	0.5	nM	CHEMBL207598
9.30	IC50	0.5	nM	BORTEZOMIB
9.29	Ki	0.51	nM	CHEMBL205757
9.26	Ki	0.55	nM	BORTEZOMIB
9.26	IC50	0.55	nM	CHEMBL3347626
9.22	Ki	0.6	nM	BORTEZOMIB
9.22	IC50	0.6	nM	CHEMBL4061262
9.22	IC50	0.6	nM	CINNABARAMIDE G
9.22	Ki	0.6	nM	CHEMBL5624541
9.19	Ki	0.65	nM	CHEMBL206413
9.15	IC50	0.7	nM	CHEMBL4104744
9.15	IC50	0.7079	nM	CHEMBL5206237
9.14	Ki	0.72	nM	CHEMBL377532
9.14	Ki	0.72	nM	CHEMBL383674
9.12	IC50	0.76	nM	CHEMBL3793848
9.10	IC50	0.8	nM	CHEMBL4747480
9.05	IC50	0.9	nM	CHEMBL4102324
9.05	IC50	0.9	nM	CHEMBL4794118
9.04	IC50	0.92	nM	CHEMBL4102324
9.03	Ki	0.93	nM	IXAZOMIB CITRATE
9.00	IC50	1	nM	CHEMBL4064404
9.00	IC50	1	nM	CHEMBL4078056
9.00	IC50	1	nM	CINNABARAMIDE A
9.00	IC50	1	nM	CHEMBL5208208
9.00	Ki	1.01	nM	CHEMBL5569360
9.00	IC50	1	nM	CHEMBL578478
8.99	IC50	1.02	nM	CHEMBL3786398
8.96	IC50	1.1	nM	CHEMBL204992
8.96	IC50	1.1	nM	CHEMBL4072652
8.96	IC50	1.1	nM	CHEMBL3218837
8.95	IC50	1.12	nM	CHEMBL3794168
8.95	IC50	1.122	nM	CHEMBL5183504
8.94	IC50	1.16	nM	CHEMBL3793238
8.94	IC50	1.15	nM	CHEMBL3793581
8.94	IC50	1.16	nM	CHEMBL3794310
8.92	IC50	1.2	nM	CHEMBL3218837
8.92	IC50	1.2	nM	CHEMBL499361
8.92	IC50	1.2	nM	CHEMBL4078693
8.92	IC50	1.2	nM	MG-132
8.92	IC50	1.202	nM	CHEMBL5196305

PubChem BioAssay actives

1462 with measured affinity, of 3363 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
[(1R)-1-[[(2S)-2-(3,4-dihydro-1H-isoquinoline-2-carbonylamino)-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1459637: Inhibition of chymotrypsin-like activity of 20S proteasome in human HL60 cells using Suc-LLVYaminoluciferin as substrate after 2 hrs by fluorescence analysis	ic50	<0.0001	uM
[(1R)-1-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1687111: Binding affinity to human 20S constitutive proteasome beta 5 subunit assessed as equilibrium constant using fluorogenic peptide Ac-WLA-AMC as substrate in presence of PA28alpha by fluorescence based microplate reader assay	ki	0.0001	uM
N-[(2S)-1-[[(3E,5S,8S,9E)-2,7-dioxo-5-propan-2-yl-1,6-diazacyclododeca-3,9-dien-8-yl]amino]-1-oxo-3-phenylpropan-2-yl]decanamide	1252350: Inhibition of proteasome beta-5 (unknown origin)	ki	0.0001	uM
[(1R)-3-methyl-1-[[(2S)-3-phenyl-2-[(3-phenylphenyl)methylcarbamoylamino]propanoyl]amino]butyl]boronic acid	1459637: Inhibition of chymotrypsin-like activity of 20S proteasome in human HL60 cells using Suc-LLVYaminoluciferin as substrate after 2 hrs by fluorescence analysis	ic50	0.0003	uM
(2S)-N-[(2S)-1-[[(2S)-1-[5-[4-(dimethylamino)phenyl]-1,3,4-oxadiazol-2-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methoxy-1-oxopropan-2-yl]-N’-(2,2-dimethylpropyl)-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0005	uM
(2S)-N-[(2S)-1-[[(2S)-1-[5-[4-(dimethylamino)phenyl]-1,3,4-oxadiazol-2-yl]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]-N’-(2,2-dimethylpropyl)-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0005	uM
Bortezomib	1382147: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-MCA as substrate measured for 1 hr by fluorescence assay	ic50	0.0005	uM
(2S)-N’-(2,2-dimethylpropyl)-N-[(2S)-1-[[(2S)-4-methyl-1-oxo-1-(5-phenyl-1,3,4-oxadiazol-2-yl)pentan-2-yl]amino]-1-oxopropan-2-yl]-2-[(3-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0006	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0006	uM
methyl (2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoate	277357: Inhibition of human 20S proteasome	ic50	0.0006	uM
[(1R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-(pyrazine-2-carbonyl)amino]-3-methylbutyl]boronic acid	2131634: Binding affinity to 20s proteosome (unknown origin) assessed as inhibition constant	ki	0.0006	uM
(2S)-N’-(2,2-dimethylpropyl)-N-[(2S)-1-[[(2S)-4-methyl-1-oxo-1-(5-phenyl-1,3,4-oxadiazol-2-yl)pentan-2-yl]amino]-1-oxopropan-2-yl]-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0007	uM
(2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide	1604186: Inhibition of 20S proteasome beta 5c (unknown origin) after 1 hr by fluorescence based assay	ic50	0.0007	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0007	uM
[(1R)-1-[[(2S)-2-[(2,5-dichlorobenzoyl)amino]-3-methylbutanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0007	uM
(2S)-N’-(2,2-dimethylpropyl)-N-[(2S)-3-methoxy-1-[[(2S)-4-methyl-1-oxo-1-(5-phenyl-1,3,4-oxadiazol-2-yl)pentan-2-yl]amino]-1-oxopropan-2-yl]-2-[(4-methylphenyl)sulfonylamino]butanediamide	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0007	uM
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxo-3-phenylpropan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0008	uM
1-N-[(2S)-5-(tert-butylamino)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-1,5-dioxopentan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1683221: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition by fluorescence assay	ic50	0.0008	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0009	uM
1-N-[(2S)-5-(tert-butylamino)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-1,5-dioxopentan-2-yl]-4-N-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1683221: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition by fluorescence assay	ic50	0.0009	uM
2-[4-(carboxymethyl)-2-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-5-oxo-1,3,2-dioxaborolan-4-yl]acetic acid	2131635: Binding affinity to 20s proteasome beta5 site (unknown origin) mediated chymotrypsin-like activity assessed as inhibition constant	ki	0.0009	uM
[(1S)-1-[[3-(3-fluorophenyl)-3-[[(1S)-1,2,3,4-tetrahydronaphthalene-1-carbonyl]amino]propanoyl]amino]-3-methylbutyl]boronic acid	1291318: Inhibition of chymotrypsin like activity of human erythrocyte-derived 20S proteasome preincubated for 10 mins using Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	0.0010	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-pyridin-2-ylpiperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0010	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-(1,3-thiazol-2-ylmethyl)piperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0010	uM
[(1R)-1-[[(2S)-2-[(2,5-dichlorobenzoyl)amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0010	uM
N-[(2S)-1-[[(3E,5S,8S)-5-benzyl-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl]amino]-1-oxo-3-phenylpropan-2-yl]decanamide	2108291: Inhibition of 20S proteasome beta-5 in human erythrocytes using Suc-LLVY-AMC as substrate by AK-740 assay	ki	0.0010	uM
(2S)-2-[[(2S)-2-[[(2S)-2-azido-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-3-phenylpropanamide	459970: Inhibition of 26S proteasome beta 5 using LLVY as substrate	ic50	0.0010	uM
(1R,4R,5S)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	277357: Inhibition of human 20S proteasome	ic50	0.0010	uM
tert-butyl (4S)-5-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ki	0.0010	uM
tert-butyl (4S)-4-(benzenesulfonamido)-5-[[(2S)-3-hydroxy-1-[[(E,3S)-5-methyl-1-methylsulfonylhex-1-en-3-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoate	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ic50	0.0011	uM
N-[(2S)-4-methyl-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxopentan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0011	uM
(1S)-N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0011	uM
(2S)-N-[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]-N’-(2,2-dimethylpropyl)-2-[[4-(pyrazine-2-carbonylamino)piperidine-1-carbonyl]amino]butanediamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0011	uM
[(1R)-1-[[(2S)-2-[(2,3-difluorobenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0011	uM
(2S)-N-[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-3-pyridin-4-ylpropan-2-yl]-N’-(2,2-dimethylpropyl)-2-[[2-(1H-indol-3-yl)-2-oxoacetyl]amino]butanediamide	1436355: Inhibition of 20s constitutive proteasome chymotrypsin-like activity in human erythrocyte using Ac-WLA-AMC as substrate in presence of proteasomal activator 28alpha by fluorimetric method	ic50	0.0011	uM
N-[(2S)-1-[[(1R)-2-(4-methylphenyl)-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0012	uM
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0012	uM
(2S)-N-[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]-N’-(2,2-dimethylpropyl)-2-[[4-[(4-fluorobenzoyl)amino]piperidine-1-carbonyl]amino]butanediamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0012	uM
[(1R)-1-[[(2S)-2-[(2,3-dichlorobenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1864383: Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis	ic50	0.0012	uM
[(1R)-3-methyl-1-[[(2S)-3-phenyl-2-[[(1S)-1,2,3,4-tetrahydronaphthalene-1-carbonyl]amino]propanoyl]amino]butyl]boronic acid	1291318: Inhibition of chymotrypsin like activity of human erythrocyte-derived 20S proteasome preincubated for 10 mins using Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	0.0012	uM
benzyl N-[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]carbamate	1515537: Inhibition of chymotrypsin like activity of 26S proteasome beta 5 subunit (unknown origin) by fluorescence assay	ic50	0.0012	uM
(1R,4R,5S)-4-(2-chloroethyl)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	1853759: Inhibition of 20S proteasome (unknown origin) by fluorescence based assay	ic50	0.0013	uM
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-3-naphthalen-1-yl-1-oxopropan-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0013	uM
(1S)-N-[(2S)-1-[[(1R)-2-(4-fluorophenyl)-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0013	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-1-oxo-4-phenylbutan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1325161: Inhibition of chymotrypsin-like activity of human 20S proteasome preincubated for 15 mins followed by addition of Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence analysis	ic50	0.0014	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-5-(2,2-dimethylpropylamino)-1,5-dioxopentan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1683221: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition by fluorescence assay	ic50	0.0014	uM
benzyl N-[(2S,3S)-1-[[(2S)-4-(2,2-dimethylpropylamino)-1-[[(2S)-1-[[(E,3S)-5-methyl-1-methylsulfonylhex-1-en-3-yl]amino]-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate	264535: Inhibition of chymotrypsin-like proteasome activity of human 20S proteasome	ic50	0.0015	uM
N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxo-3-phenylpropan-2-yl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide	1295429: Inhibition of chymotrypsin like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric analysis	ic50	0.0015	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-(4-fluorophenyl)piperidine-1,4-dicarboxamide	1436349: Inhibition of chymotrypsin-like activity of human 20S proteasome pretreated for 15 mins followed by Suc-Leu-Leu-Val-Tyr-AMC substrate addition by fluorescence assay	ic50	0.0015	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases reaction, increases reaction, affects expression, affects cotreatment (+3 more)	5
Resveratrol	affects cotreatment, increases expression, affects reaction, decreases secretion, decreases expression	3
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases expression, decreases expression, increases reaction, affects cotreatment	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
bisphenol A	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tanshinone	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
sibutramine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CV 6504	decreases reaction, increases expression	1
chloropicrin	affects expression	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
stattic	increases expression, decreases expression, decreases reaction	1
WP1066	decreases reaction, increases expression, decreases expression	1
EGFR tyrosine kinase inhibitor 324674	decreases reaction, increases expression	1
bisphenol AF	increases expression	1
Bortezomib	affects binding, decreases response to substance, affects response to substance	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Clozapine	affects cotreatment, increases expression	1

ChEMBL screening assays

486 unique, capped per target: 466 binding, 15 admet, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3222879	Binding	Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 90 mins by fluorescence assay	Oxathiazole-2-one derivative of bortezomib: Synthesis, stability and proteasome inhibition activity — Medchemcomm
CHEMBL4736581	ADMET	Inhibition of human 20S proteasome stably expressed in HEK293 cells at 5 to 50 uM using succinyl-LLVY-AMC as substrate preincubated for 30 mins followed by substrate addition and measured at 3 mins interval for 30 mins by fluorescence assay	A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells. — Eur J Med Chem
CHEMBL834792	Functional	Inhibitory concentration to inhibit trypsin-like activity of 20S proteasome from human leukemia HL-60 cells was determined	Structure-based design of derivatives of tyropeptin A as the potent and selective inhibitors of mammalian 20S proteasome. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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