PSMB11

Summary

PSMB11 (proteasome subunit beta 11, HGNC:31963) is a protein-coding gene on chromosome 14q11.2, encoding Proteasome subunit beta type-11 (A5LHX3). The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.

Proteasomes generate peptides that are presented by major histocompatibility complex (MHC) I molecules to other cells of the immune system. Proteolysis is conducted by 20S proteasomes, complexes of 28 subunits arranged as a cylinder in 4 heteroheptameric rings: alpha-1 to -7, beta-1 to -7, beta-1 to -7, and alpha-1 to -7. The catalytic subunits are beta-1 (PSMB6; MIM 600307), beta-2 (PSMB7; MIM 604030), and beta-5 (PSMB5; MIM 600306). Three additional subunits, beta-1i (PSMB9; MIM 177045), beta-2i (PSMB10; MIM 176847), and beta-5i (PSMB8; MIM 177046), are induced by gamma-interferon (IFNG; MIM 147570) and are preferentially incorporated into proteasomes to make immunoproteasomes. PSMB11, or beta-5t, is a catalytic subunit expressed exclusively in cortical thymic epithelial cells (Murata et al., 2007 [PubMed 17540904]).

Source: NCBI Gene 122706 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 70 total — 1 pathogenic
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001099780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31963
Approved symbol	PSMB11
Name	proteasome subunit beta 11
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	beta5t
Ensembl gene	ENSG00000222028
Ensembl biotype	protein_coding
OMIM	611137
Entrez	122706

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000408907

RefSeq mRNA: 1 — MANE Select: NM_001099780 NM_001099780

CCDS: CCDS41923

Canonical transcript exons

ENST00000408907 — 1 exons

Exon	Start	End
ENSE00001734086	23042212	23044060

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 41.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0315 / max 29.8245, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138873	0.0315	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	41.29	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skeletal muscle tissue	UBERON:0001134	36.32	gold quality
lymph node	UBERON:0000029	36.22	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
sural nerve	UBERON:0015488	35.85	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	33.22	gold quality
bone marrow	UBERON:0002371	32.90	gold quality
right uterine tube	UBERON:0001302	32.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
blood	UBERON:0000178	31.60	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.29	gold quality
muscle of leg	UBERON:0001383	29.03	gold quality
urinary bladder	UBERON:0001255	28.68	gold quality
gastrocnemius	UBERON:0001388	28.37	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.94	gold quality
leukocyte	CL:0000738	27.91	gold quality
primary visual cortex	UBERON:0002436	27.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	27.42	gold quality
left testis	UBERON:0004533	27.38	silver quality
left adrenal gland cortex	UBERON:0035825	27.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.35	gold quality
islet of Langerhans	UBERON:0000006	27.30	gold quality
right adrenal gland cortex	UBERON:0035827	27.17	gold quality
tonsil	UBERON:0002372	27.05	gold quality
calcaneal tendon	UBERON:0003701	26.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-79	yes	450.60
E-ANND-3	no	0.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PSMB11, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4725-5P	98.67	65.42	628

Literature-anchored findings (GeneRIF, showing 6)

• results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection (PMID:17540904)
• Human beta5t was expressed in approximately 80% of cortical thymic epithelial cells and some cortical dendritic cells (PMID:19289856)
• Proteasome beta5t is expressed in most type B and in some type AB thymomas and is a marker useful in differentiating type B3 thymomas from thymic carcinomas when used in combination with other diagnostic markers. (PMID:21836487)
• provide the first evidence that the mechanism underlying BTZ resistance in these tumor cells is impaired binding of BTZ to the mutant beta5 subunit of the proteasome (PMID:21941364)
• Histological diversity of type AB thymoma correlates with expression of a functional marker beta5t and abundance of TdT-positive lymphocytes. (PMID:24293611)
• We analysed thymic tissues from patients with trisomy 13 (n = 4), trisomy 18 (n = 14) and trisomy 21 (n = 13) for histological alterations, and for the expression of functionally important molecules such as beta5t, a thymoproteasome subunit, and cathepsins. (PMID:25556590)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb11b	ENSDARG00000068086
danio_rerio	psmb11a	ENSDARG00000108530
mus_musculus	Psmb11	ENSMUSG00000072423
rattus_norvegicus	Psmb11	ENSRNOG00000072044
drosophila_melanogaster	Prosbeta1	FBGN0010590
caenorhabditis_elegans		WBGENE00003947

Paralogs (18): PSMB1 (ENSG00000008018), PSMA4 (ENSG00000041357), PSMA3 (ENSG00000100567), PSMB5 (ENSG00000100804), PSMA6 (ENSG00000100902), PSMA7 (ENSG00000101182), PSMA2 (ENSG00000106588), PSMB2 (ENSG00000126067), PSMA1 (ENSG00000129084), PSMB7 (ENSG00000136930), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit beta type-11 — A5LHX3 (reviewed: A5LHX3)

Alternative names: Proteasome subunit beta-5t

All UniProt accessions (1): A5LHX3

UniProt curated annotations — full annotation on UniProt →

Function. The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Incorporated instead of PSMB5 or PSMB8, this unit reduces the chymotrypsin-like activity of the proteasome. Plays a pivotal role in development of CD8-positive T cells.

Subunit / interactions. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Incorporated instead of PSMB5 and PSMB8.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the peptidase T1B family.

RefSeq proteins (1): NP_001093250* (*=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 (6 total): region of interest 2, propeptide 1, chain 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5LHX3-F1	80.90	0.63

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): 50 (nucleophile)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 72 (showing top): KEGG_PROTEASOME, GOBP_THYMIC_T_CELL_SELECTION, GOBP_T_CELL_HOMEOSTASIS, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_T_CELL_SELECTION, GOBP_LEUKOCYTE_HOMEOSTASIS, GOBP_HOMEOSTATIC_PROCESS, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_PROTEOLYSIS

GO Biological Process (5): proteolysis (GO:0006508), T cell differentiation in thymus (GO:0033077), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), CD8-positive, alpha-beta T cell differentiation (GO:0043374), 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 (6): nucleus (GO:0005634), cytosol (GO:0005829), proteasome core complex, beta-subunit complex (GO:0019774), proteasome complex (GO:0000502), cytoplasm (GO:0005737), proteasome core complex (GO:0005839)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular anatomical structure	2
intracellular protein-containing complex	2
protein metabolic process	1
T cell differentiation	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
CD8-positive, alpha-beta T cell activation	1
alpha-beta T cell differentiation	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
intracellular membrane-bounded organelle	1
cytoplasm	1
proteasome core complex	1
protein-containing complex	1
endopeptidase complex	1
proteasome complex	1
catalytic complex	1

Protein interactions and networks

STRING

1075 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB11	PSMB10	P40306	962
PSMB11	PSMB9	P28065	939
PSMB11	PRSS16	Q9NQE7	809
PSMB11	FOXN1	O15353	672
PSMB11	PSMA8	Q8TAA3	654
PSMB11	AIRE	O43918	597
PSMB11	PSME4	Q14997	597
PSMB11	LY75	O60449	589
PSMB11	POMP	Q9Y244	545
PSMB11	PLET1	Q6UQ28	541
PSMB11	CTRL	P40313	508
PSMB11	CCL25	O15444	474
PSMB11	CTSL	P07711	465
PSMB11	PSME3	P61289	455
PSMB11	PSMD4	P55036	453

IntAct

18 interactions, top by confidence:

A	B	Type	Score
HGS	PSMB11	psi-mi:“MI:0915”(physical association)	0.560
PITX1	PSMB11	psi-mi:“MI:0915”(physical association)	0.560
PSMB11	PROP1	psi-mi:“MI:0915”(physical association)	0.560
PSMB11	HGS	psi-mi:“MI:0915”(physical association)	0.560
PSMB11	TLX3	psi-mi:“MI:0915”(physical association)	0.560
PSMB11	PITX1	psi-mi:“MI:0915”(physical association)	0.560
PSMB11	ATG5	psi-mi:“MI:0915”(physical association)	0.560
PROP1	PSMB11	psi-mi:“MI:0915”(physical association)	0.000
ATG5	PSMB11	psi-mi:“MI:0915”(physical association)	0.000
TLX3	PSMB11	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): PSMB11 (Two-hybrid), PSMB11 (Two-hybrid), PSMB11 (Two-hybrid), PSMB11 (Two-hybrid), PSMB11 (Two-hybrid), PSMB11 (Affinity Capture-RNA), PSMB11 (Proximity Label-MS), PSMB11 (Protein-peptide)

ESM2 similar proteins: A0JP70, A1XQU1, A5LHX3, O14976, O23712, O24361, O35955, O43304, O55234, O95248, O95382, O95398, P28062, P28063, P28064, P28072, P28074, P28075, P30656, P34065, P40306, P51656, P51657, P54265, P70195, Q09013, Q0P595, Q2TBP0, Q32KL2, Q3MHN0, Q3T0T1, Q3T112, Q4KM35, Q54BC8, Q5R8S2, Q5W416, Q60692, Q6NYX6, Q6ZPG2, Q7DLS1

Diamond homologs: A0RXV1, A1RSJ8, A1RWY6, A1RX71, A1XQU1, A2BN27, A2SS78, A3CUS9, A3DN27, A3MS44, A3MXQ6, A4FYA5, A4WH05, A4WMZ0, A4YIE0, A5LHX3, A6UT20, A6VK02, A7I841, A8M8R5, A8MBW0, A9A2U7, A9A788, B1L6S7, B1YDJ0, B5IEE5, B6YSW2, B6YXV3, B8D683, B8GG66, B9LTS6, C3MRE5, C3MY41, C3MZI0, C3N7K2, C3NFX2, C4KIR0, C5A2D5, C5A7L1, C6A459

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1676204	NC_000014.8:g.(21162263_36986276)_(36987308_50713602)del	Pathogenic

SpliceAI

197 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23043123:GT:G	donor_gain	0.9800
14:23043136:G:GT	donor_gain	0.9800
14:23043101:G:GT	donor_gain	0.9700
14:23042823:G:GT	donor_gain	0.9600
14:23043084:A:AG	donor_gain	0.9600
14:23043113:G:T	donor_gain	0.9600
14:23042997:G:GT	donor_gain	0.9500
14:23043112:GGAC:G	donor_gain	0.9500
14:23043000:G:GT	donor_gain	0.9400
14:23043052:A:G	donor_gain	0.9400
14:23043125:G:GG	donor_gain	0.9300
14:23042872:A:AG	donor_gain	0.9200
14:23042884:GGGGC:G	donor_gain	0.9200
14:23043077:G:T	donor_gain	0.8800
14:23043119:GACG:G	donor_gain	0.8800
14:23043078:G:T	donor_gain	0.8700
14:23043113:GAC:G	donor_gain	0.8300
14:23043085:C:G	donor_gain	0.8200
14:23043536:T:TA	acceptor_gain	0.7500
14:23043078:G:GT	donor_gain	0.7300
14:23042914:A:T	donor_gain	0.7200
14:23042238:G:GT	donor_gain	0.6900
14:23043121:CGGT:C	donor_gain	0.6800
14:23043122:GGTG:G	donor_gain	0.6800
14:23043048:G:GT	donor_gain	0.6600
14:23043164:G:T	donor_gain	0.6200
14:23043119:G:GT	donor_gain	0.6100
14:23043144:T:A	donor_gain	0.6100
14:23043120:ACGGT:A	donor_gain	0.6000
14:23043143:T:TA	donor_gain	0.5800

AlphaMissense

1907 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23042389:T:C	F55S	0.984
14:23042413:C:A	A63D	0.980
14:23042471:G:C	K82N	0.980
14:23042471:G:T	K82N	0.980
14:23042394:T:C	F57L	0.979
14:23042396:C:A	F57L	0.979
14:23042396:C:G	F57L	0.979
14:23042776:C:A	A184D	0.976
14:23042415:G:C	A64P	0.974
14:23042839:C:A	A205D	0.972
14:23042535:T:A	W104R	0.970
14:23042535:T:C	W104R	0.970
14:23042388:T:C	F55L	0.969
14:23042390:C:A	F55L	0.969
14:23042390:C:G	F55L	0.969
14:23042418:G:C	A65P	0.969
14:23042713:T:A	V163D	0.969
14:23042848:C:A	A208D	0.969
14:23042416:C:A	A64E	0.968
14:23042860:C:A	A212D	0.967
14:23042873:T:A	D216E	0.965
14:23042873:T:G	D216E	0.965
14:23042421:G:C	D66H	0.964
14:23042500:G:A	G92D	0.964
14:23042859:G:C	A212P	0.964
14:23042901:T:C	F226L	0.963
14:23042903:C:A	F226L	0.963
14:23042903:C:G	F226L	0.963
14:23042374:C:T	T50I	0.962
14:23042422:A:T	D66V	0.962

dbSNP variants (sampled 300 via entrez): RS1000042249 (14:23044185 T>G), RS1001760648 (14:23041779 G>A), RS1002822903 (14:23042740 G>A,C,T), RS1003719609 (14:23043584 C>G), RS1003771963 (14:23043799 A>G), RS1004652382 (14:23041483 C>G,T), RS1004903352 (14:23044339 A>AGTTGCT), RS1006015118 (14:23041883 T>A,C,G), RS1006611856 (14:23043202 G>A,T), RS1007035724 (14:23041673 T>A), RS1008613872 (14:23043429 C>T), RS1008722757 (14:23040756 G>A), RS1009189838 (14:23040924 A>G), RS1012365470 (14:23043895 C>G), RS1012419623 (14:23044106 C>A)

Disease associations

OMIM: gene MIM:611137 | disease phenotypes: MIM:610978

GenCC curated gene-disease

Mondo (1): brain-lung-thyroid syndrome (MONDO:0012593)

Orphanet (1): Brain-lung-thyroid syndrome (Orphanet:209905)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004621_65	Red cell distribution width	2.000000e-20
GCST006804_180	Red cell distribution width	2.000000e-08
GCST90002404_388	Red cell distribution width	3.000000e-23

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567034	Choreoathetosis, Hypothyroidism, And Neonatal Respiratory Distress (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831201 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 41,720 (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
CHEMBL2141296	IXAZOMIB	3	6,022
CHEMBL371405	MARIZOMIB	3	7,332
CHEMBL2103884	OPROZOMIB	2	2,738

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

ChEMBL bioactivities

312 potent at pChembl≥5 of 336 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CINNABARAMIDE G
9.22	Ki	0.6	nM	CHEMBL5624541
9.22	Ki	0.6	nM	BORTEZOMIB
9.04	IC50	0.92	nM	CHEMBL4102324
9.00	IC50	1	nM	CINNABARAMIDE A
8.89	IC50	1.3	nM	MARIZOMIB
8.82	IC50	1.5	nM	CHEMBL4460323
8.70	IC50	2	nM	CHEMBL307387
8.66	IC50	2.2	nM	CHEMBL5419917
8.62	IC50	2.4	nM	CHEMBL4517600
8.62	IC50	2.4	nM	BORTEZOMIB
8.62	IC50	2.4	nM	CHEMBL5413513
8.60	IC50	2.5	nM	CHEMBL4587036
8.59	IC50	2.56	nM	BORTEZOMIB
8.57	IC50	2.7	nM	CHEMBL3237863
8.57	IC50	2.7	nM	CHEMBL5394365
8.52	IC50	3	nM	BORTEZOMIB
8.47	IC50	3.4	nM	CHEMBL4444107
8.47	IC50	3.4	nM	CHEMBL6143686
8.46	IC50	3.43	nM	CHEMBL5197285
8.44	IC50	3.6	nM	CHEMBL4541038
8.41	IC50	3.9	nM	CHEMBL3237862
8.41	IC50	3.9	nM	CHEMBL4547405
8.40	IC50	4	nM	CHEMBL5406440
8.39	IC50	4.1	nM	CHEMBL3237864
8.39	IC50	4.1	nM	CHEMBL3237867
8.39	IC50	4.03	nM	CHEMBL5171225
8.37	IC50	4.28	nM	CHEMBL4581126
8.34	IC50	4.6	nM	CHEMBL4542373
8.34	IC50	4.6	nM	CHEMBL4558648
8.32	IC50	4.8	nM	CHEMBL3237873
8.32	IC50	4.8	nM	CHEMBL4467618
8.30	IC50	5	nM	CHEMBL5398681
8.29	IC50	5.1	nM	CHEMBL3237865
8.29	IC50	5.15	nM	CHEMBL5186240
8.28	IC50	5.2	nM	CHEMBL5429323
8.28	IC50	5.2	nM	CHEMBL5431451
8.25	IC50	5.6	nM	CHEMBL5423645
8.24	IC50	5.7	nM	CHEMBL3237866
8.24	IC50	5.7	nM	CHEMBL3237860
8.23	IC50	5.9	nM	CHEMBL3237868
8.22	IC50	6	nM	CINNABARAMIDE F
8.22	IC50	6	nM	CHEMBL5412037
8.22	IC50	6	nM	CHEMBL74336
8.20	IC50	6.3	nM	CHEMBL5440712
8.19	IC50	6.4	nM	CHEMBL4447701
8.19	IC50	6.4	nM	CHEMBL4435814
8.19	IC50	6.5	nM	CHEMBL4436430
8.19	IC50	6.5	nM	IXAZOMIB
8.16	IC50	6.91	nM	BORTEZOMIB

PubChem BioAssay actives

280 with measured affinity, of 810 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
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
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	1903224: 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 measured by fluorescence assay	ic50	0.0009	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
(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
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
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-2-cyclopentyl-10-(1,3-dioxoisoindol-2-yl)decanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0020	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0022	uM
4-N-(4-benzoylphenyl)-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]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0024	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0024	uM
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(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]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0025	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0027	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0027	uM
4-N-(4-fluorophenyl)-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]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0034	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methyl-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1903224: 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 measured by fluorescence assay	ic50	0.0034	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-pyridin-3-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0036	uM
4-N-(1,3-benzothiazol-2-yl)-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]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0039	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0039	uM
[(1R)-1-[[2-[(2,5-dibromobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0040	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1903224: 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 measured by fluorescence assay	ic50	0.0040	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(2S)-3-(4-hydroxyphenyl)-1-[[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0043	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-(1,3,4-thiadiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-chlorophenyl)-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]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-methoxyphenyl)-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]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0048	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0050	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0051	uM
(2S)-N’-(2,2-dimethylpropyl)-2-[[4-[methyl(pyridine-3-carbonyl)amino]piperidine-1-carbonyl]amino]-N-[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]butanediamide	1903224: 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 measured by fluorescence assay	ic50	0.0052	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0056	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
benzyl N-[(2S)-1-[[(2R)-1-[(1R,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]-4-phenylbutan-2-yl]amino]-1-oxopropan-2-yl]carbamate	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
(2S)-2-[(2,5-dichlorobenzoyl)amino]-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0059	uM
(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]sulfanylpropanoic acid	277357: Inhibition of human 20S proteasome	ic50	0.0060	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0060	uM
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-10-cyano-2-cyclopentyldecanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0060	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0063	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-(1,2-oxazol-3-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0064	uM
(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pentanamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0064	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-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0065	uM
Ixazomib	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0065	uM
4-N-(4-chlorophenyl)-1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methylpiperidine-1,4-dicarboxamide	1903224: 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 measured by fluorescence assay	ic50	0.0069	uM
(2S)-N-[(2S,3R,4R)-3-hydroxy-5-[[(2S)-1-[(2-hydroxy-4-methoxyphenyl)methylamino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxo-1-phenyl-4-[(3,4,5-trimethoxyphenyl)methylamino]pentan-2-yl]-3,3-dimethyl-2-[(2-naphthalen-1-ylacetyl)amino]butanamide	3027: Tested in vitro for inhibition of chymotrypsin like activity of purified human 20S proteasome	ic50	0.0070	uM
Carfilzomib	1770085: Inhibition of human 20S proteasome chymotrypsin-like activity in human RPMI-8226 cells using Suc-LLVY-AMC as fluorogenic substrate incubated for 3 hrs by fluorescence assay	ic50	0.0070	uM
(2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-naphthalen-1-ylacetyl)amino]propanoyl]amino]-N-[1-(4-hydroxyphenyl)-3-oxopropan-2-yl]-3-methylbutanamide	248827: Inhibitory concentration to inhibit chymotrypsin-like activity of 20S proteasome prepared from human leukemia HL-60 cells was determined	ic50	0.0070	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-(pyrazine-2-carbonylamino)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0071	uM

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation	2
dimethylselenide	decreases expression, increases expression, increases oxidation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Reactive Oxygen Species	increases oxidation, decreases expression, increases expression	1

ChEMBL screening assays

168 unique, capped per target: 159 binding, 6 admet, 3 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.