PSMB7

Summary

PSMB7 (proteasome 20S subunit beta 7, HGNC:9544) is a protein-coding gene on chromosome 9q33.3, encoding Proteasome subunit beta type-7 (Q99436). 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 96.8% 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. The encoded protein is a member of the proteasome B-type family, also known as the T1B family, and is a 20S core beta subunit in the proteasome. Expression of this catalytic subunit is downregulated by gamma interferon, and proteolytic processing is required to generate a mature subunit. A pseudogene of this gene is located on the long arm of chromosome 14.

Source: NCBI Gene 5695 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• GTEx eGene: eQTL in 33 tissues, sQTL in 3 (q < 0.05)
• ChEMBL bioactivity: 5 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 96.8% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.43 (moderately constrained)
• MANE Select transcript: NM_002799
• Interaction hub: 2,598 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9544
Approved symbol	PSMB7
Name	proteasome 20S subunit beta 7
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	Z
Ensembl gene	ENSG00000136930
Ensembl biotype	protein_coding
OMIM	604030
Entrez	5695

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 20 protein_coding, 8 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000259457

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1, TSL 5: 4

ENST00000259457, ENST00000441097, ENST00000466951, ENST00000474081, ENST00000478817, ENST00000498485, ENST00000894502, ENST00000894503, ENST00000894504, ENST00000916856, ENST00000916857, ENST00000916858, ENST00000916859, ENST00000916860, ENST00000916861, ENST00000978529, ENST00000978530, ENST00000978531, ENST00000978532, ENST00001041013, ENST00001058402, ENST00001058403, ENST00001058412, ENST00001058414, ENST00001102265, ENST00001102266, ENST00001105604, ENST00001105605, ENST00001116006, ENST00001116007, ENST00001130640, ENST00001135675

RefSeq mRNA: 1 — MANE Select: NM_002799 NM_002799

CCDS: CCDS6855

Canonical transcript exons

ENST00000259457 — 8 exons

Exon	Start	End
ENSE00000726881	124405317	124405432
ENSE00001866322	124415364	124415442
ENSE00003474631	124356764	124356915
ENSE00003516673	124414842	124414935
ENSE00003539655	124353465	124353709
ENSE00003648784	124412352	124412492
ENSE00003677239	124384598	124384656
ENSE00003677426	124413908	124414005

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 150.5938 / max 1109.3557, expressed in 1823 samples.

Highest expression (Bgee): ganglionic eminence, cortical plate, ventricular zone, testis, embryo.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PSMB7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 36 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	2.2e-13	+0.14	9:124354663:C:T
Esophagus Muscularis	eqtl	3.8e-12	+0.17	9:124383011:A:C
Thyroid	eqtl	6.6e-12	+0.13	9:124421788:A:G
Adipose Subcutaneous	eqtl	8.4e-11	+0.14	9:124415457:G:C
Brain Caudate basal ganglia	sqtl	3.3e-09	+0.62	9:124374365:G:C
Brain Cerebellum	eqtl	6.0e-09	-0.25	9:124413319:G:C
Colon Transverse	eqtl	1.7e-08	+0.16	9:124415457:G:C
Nerve Tibial	eqtl	3.8e-08	+0.11	9:124415457:G:C
Colon Sigmoid	eqtl	8.4e-08	+0.19	9:124404281:G:GT
Pancreas	eqtl	1.7e-07	+0.18	9:124421788:A:G
Stomach	eqtl	1.9e-07	+0.16	9:124404281:G:GT
Breast Mammary Tissue	eqtl	2.5e-07	+0.10	9:124369741:A:G
Brain Nucleus accumbens basal ganglia	sqtl	4.0e-07	-0.60	9:124323850:T:C
Lung	eqtl	9.2e-07	+0.11	9:124415457:G:C
Brain Cerebellar Hemisphere	eqtl	1.3e-06	-0.15	9:124415987:G:T
Adipose Visceral Omentum	eqtl	1.7e-06	+0.10	9:124421788:A:G
Artery Aorta	eqtl	3.2e-06	-0.12	9:124413319:G:C
Ovary	eqtl	4.3e-06	-0.30	9:124374365:G:C
Cells Cultured fibroblasts	eqtl	2.4e-05	-0.16	9:124360479:C:G
Testis	eqtl	7.0e-05	+0.09	9:124421788:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
102425	150.5938	1823

Top tissues by expression

showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.28	gold quality
cortical plate	UBERON:0005343	99.10	gold quality
ventricular zone	UBERON:0003053	98.98	gold quality
left testis	UBERON:0004533	98.82	gold quality
right testis	UBERON:0004534	98.82	gold quality
embryo	UBERON:0000922	98.81	gold quality
right adrenal gland	UBERON:0001233	98.65	gold quality
left adrenal gland	UBERON:0001234	98.59	gold quality
skin of leg	UBERON:0001511	98.54	gold quality
right adrenal gland cortex	UBERON:0035827	98.53	gold quality
left adrenal gland cortex	UBERON:0035825	98.50	gold quality
adrenal tissue	UBERON:0018303	98.47	gold quality
skin of abdomen	UBERON:0001416	98.44	gold quality
stromal cell of endometrium	CL:0002255	98.39	gold quality
apex of heart	UBERON:0002098	98.36	gold quality
zone of skin	UBERON:0000014	98.31	gold quality
adrenal gland	UBERON:0002369	98.30	gold quality
body of pancreas	UBERON:0001150	98.29	gold quality
right frontal lobe	UBERON:0002810	98.29	gold quality
adrenal cortex	UBERON:0001235	98.25	gold quality
adult organism	UBERON:0007023	98.21	gold quality
prefrontal cortex	UBERON:0000451	98.19	gold quality
testis	UBERON:0000473	98.16	gold quality
rectum	UBERON:0001052	98.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.13	gold quality
nucleus accumbens	UBERON:0001882	98.11	gold quality
islet of Langerhans	UBERON:0000006	98.08	gold quality
caudate nucleus	UBERON:0001873	98.08	gold quality
right lobe of liver	UBERON:0001114	98.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.04	gold quality
monocyte	CL:0000576	98.03	gold quality
smooth muscle tissue	UBERON:0001135	98.03	gold quality
heart right ventricle	UBERON:0002080	98.03	gold quality
heart left ventricle	UBERON:0002084	98.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.02	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.00	gold quality
body of stomach	UBERON:0001161	97.99	gold quality
cardiac ventricle	UBERON:0002082	97.99	gold quality
cingulate cortex	UBERON:0003027	97.99	gold quality
right atrium auricular region	UBERON:0006631	97.99	gold quality
gingival epithelium	UBERON:0001949	97.98	gold quality
upper leg skin	UBERON:0004262	97.96	gold quality
amygdala	UBERON:0001876	97.94	gold quality
anterior cingulate cortex	UBERON:0009835	97.94	gold quality
gastrocnemius	UBERON:0001388	97.90	gold quality
minor salivary gland	UBERON:0001830	97.88	gold quality
esophagus mucosa	UBERON:0002469	97.88	gold quality
mononuclear cell	CL:0000842	97.87	gold quality
biceps brachii	UBERON:0001507	97.85	gold quality
leukocyte	CL:0000738	97.84	gold quality
descending thoracic aorta	UBERON:0002345	97.84	gold quality
gall bladder	UBERON:0002110	97.83	gold quality
putamen	UBERON:0001874	97.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.79	gold quality
esophagus	UBERON:0001043	97.78	gold quality
left coronary artery	UBERON:0001626	97.76	gold quality
ectocervix	UBERON:0012249	97.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.75	gold quality
popliteal artery	UBERON:0002250	97.74	gold quality
tibial artery	UBERON:0007610	97.74	gold quality
peripheral nervous system	UBERON:0000010	97.73	gold quality
tibial nerve	UBERON:0001323	97.73	gold quality
mouth mucosa	UBERON:0003729	97.73	gold quality
lower esophagus	UBERON:0013473	97.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.73	gold quality
gingiva	UBERON:0001828	97.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.71	gold quality
artery	UBERON:0001637	97.70	gold quality
type B pancreatic cell	CL:0000169	97.68	gold quality
aorta	UBERON:0000947	97.68	gold quality
thoracic aorta	UBERON:0001515	97.68	gold quality
ascending aorta	UBERON:0001496	97.67	gold quality
body of uterus	UBERON:0009853	97.67	gold quality
metanephros cortex	UBERON:0010533	97.67	gold quality
endocervix	UBERON:0000458	97.63	gold quality
saliva-secreting gland	UBERON:0001044	97.61	gold quality
left ovary	UBERON:0002119	97.59	gold quality
coronary artery	UBERON:0001621	97.58	gold quality
omental fat pad	UBERON:0010414	97.58	gold quality
muscle of leg	UBERON:0001383	97.57	gold quality
right lung	UBERON:0002167	97.57	gold quality
peritoneum	UBERON:0002358	97.57	gold quality
mucosa of transverse colon	UBERON:0004991	97.57	gold quality
right ovary	UBERON:0002118	97.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.52	gold quality
mucosa of stomach	UBERON:0001199	97.51	gold quality
amniotic fluid	UBERON:0000173	97.50	gold quality
sigmoid colon	UBERON:0001159	97.50	gold quality
right coronary artery	UBERON:0001625	97.50	gold quality
skin of hip	UBERON:0001554	97.48	gold quality
spinal cord	UBERON:0002240	97.43	gold quality
upper lobe of left lung	UBERON:0008952	97.42	gold quality
transverse colon	UBERON:0001157	97.41	gold quality
hypothalamus	UBERON:0001898	97.41	gold quality
gluteal muscle	UBERON:0002000	97.41	gold quality
liver	UBERON:0002107	97.41	gold quality
left uterine tube	UBERON:0001303	97.39	gold quality
ovary	UBERON:0000992	97.36	gold quality
vermiform appendix	UBERON:0001154	97.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-53	no	647.30
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	259.6
Caudate putamen	tissue	258.9
Liver	tissue	208.1	high
Skeletal muscle	tissue	205.4	medium
Tongue	tissue	191.7
Bone marrow	tissue	178.9	medium
Heart muscle	tissue	173.2	high
Spinal cord	tissue	167.6
Pons	tissue	156.7
Medulla oblongata	tissue	151.6
Thalamus	tissue	145.6
Midbrain	tissue	141.2
Kidney	tissue	140.7	high
Epididymis	tissue	138.8	high
Thymus	tissue	137.6
Substantia nigra	tissue	137.1
Superior colliculi	tissue	135.8
Parathyroid gland	tissue	134.6	high
Adrenal gland	tissue	129.9	high
Locus coeruleus	tissue	129.6
Hippocampal formation	tissue	129.3
Corpus callosum	tissue	128.2
Skin 1	tissue	123.4	high
Putamen	tissue	121.8
Testis	tissue	119.4	high
Ovary	tissue	119.4	medium
Septum	tissue	118.4
Cerebral cortex	tissue	117.4	high
Somatosensory cortex	tissue	117.4
Hypothalamus	tissue	116.9
Tonsil	tissue	116.7	high
Pancreas	tissue	116.0	high
Breast	tissue	114.7	high
Placenta	tissue	112.9	high
Nucleus accumbens	tissue	112.7
Periaqueductal gray	tissue	112.2
Hippocampus	tissue	111.6	medium
Ventral forebrain	tissue	111.1
Occipital cortex	tissue	110.2
Esophagus	tissue	109.5	high
Motor cortex	tissue	109.1
Prefrontal cortex	tissue	107.8
Salivary gland	tissue	107.6	high
Lymph node	tissue	105.3	low
Temporal cortex	tissue	104.7
Retrosplenial and cingulate cortex	tissue	104.2
Urinary bladder	tissue	103.2	high
Basal ganglia	tissue	102.6	medium
Rectum	tissue	101.2	high
Adipose tissue	tissue	100.6	medium
Entorhinal cortex	tissue	100.2
Vagina	tissue	98.9	high
Appendix	tissue	98.0	medium
Retrosplenial cortex	tissue	95.7
Colon	tissue	95.1	high
Amygdala	tissue	93.4
Duodenum	tissue	92.8	medium
Small intestine	tissue	92.6	medium
Postcentral gyrus	tissue	90.4
Fallopian tube	tissue	89.0	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (167.6), Dorsal spinal cord (143.2), Posterior thalamic nucleus (129.7), Dorsal hippocampus (129.3), Spinal trigeminal nucleus, interpolar (128.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PSMB7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

4 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-4704-5P	96.13	68.67	608

Functional genomics

gnomAD constraint: pLI 0.994, LOEUF 0.427, missense Z 1.21 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000259457 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
9:124,353,601–124,414,891	213 / 302.4	0.70	no
9:124,414,892–124,415,425	62 / 43.9	1.41	no
DepMap (CRISPR cell-line fitness): dependent in 96.8% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): AsPC-1 (-2.365), SW 1990 (-2.167), DK-MG (-2.092), SNU-886 (-2.01), SK-HEP-1 (-2.001), NCI-H226 (-1.977), HPAF-II (-1.97), RH-41 (-1.937), RERF-LC-Sq1 (-1.916), LU99 (-1.905), KP-N-SI9s (-1.892), BHT-101 (-1.888), RERF-LC-AI (-1.849), HCC38 (-1.841), NCI-H2052 (-1.821).

Literature-anchored findings (GeneRIF, showing 8)

• Low protein Z levels but not protein Z gene G79A polymorphism are a risk factor for ischemic stroke. (PMID:18378283)
• A previously unreported sporadic missense mutation within exon 8 is described in a patient with very low protein Z levels. (PMID:18462727)
• PSB7, PRDX1, and SRP9 up-regulation as candidate biomarkers of colon cancer is discovered (PMID:18549262)
• ZPI functions like other serpins to regulate the activity of FXa but in a manner uniquely dependent on protein Z, procoagulant membranes, and pH (PMID:18768472)
• we have identified and characterized a new phosphorylated isoform of the human 20S proteasome b7 subunit and showed its differential expression in tumor vs. normal cell lines (PMID:19645816)
• high PSMB7 expression is associated with anthracycline resistance in breast cancer. (PMID:20010949)
• reduced protein levels in patients with rheumatoid arthritis in association with disease progression (PMID:21713324)
• Studied the associations of Protein Z (PROZ G79A) and Endothelin-1 (EDN1 G5665T) polymorphisms with the clinical features of sickle cell disease (SCD) in a cohort of Egyptian children with SCD. (PMID:28548215)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb7	ENSDARG00000037962
mus_musculus	Psmb7	ENSMUSG00000026750
rattus_norvegicus	Psmb7	ENSRNOG00000011732
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), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	A1XQU1	97.8%	Diamond
Bos taurus	Q2TBP0	97.8%	Diamond
Arabidopsis thaliana	O23710	97.4%	Diamond
Nicotiana tabacum	P93395	85.1%	Diamond
Schizosaccharomyces pombe 972h-	P30655	67.9%	Diamond
Dictyostelium discoideum	Q54QR2	64.2%	Diamond
Saccharomyces cerevisiae S288C	P38624	62.5%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SQN7	52.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NEK6	protein-coding	10783
ADGRD2	protein-coding	347088
NR5A1	protein-coding	2516
NR6A1	protein-coding	2649
LHX2	protein-coding	9355

Protein

Protein identifiers

Proteasome subunit beta type-7 — Q99436 (reviewed: Q99436)

Alternative names: Macropain chain Z, Multicatalytic endopeptidase complex chain Z, Proteasome subunit Z, Proteasome subunit beta-2

All UniProt accessions (3): E9KL30, Q99436, Q5TBG5

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, PSMB7 displays a trypsin-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. (Microbial infection) Interacts with HIV-1 Tat protein.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed at a low level in colonic mucosa. Up-regulated in colorectal cancer tissues.

Similarity. Belongs to the peptidase T1B family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99436-1	1	yes
Q99436-2	2

RefSeq proteins (1): NP_002790* (*=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
IPR024689	Proteasome_bsu_C	Domain
IPR029055	Ntn_hydrolases_N	Homologous_superfamily

Pfam: PF00227, PF12465

UniProt features (32 total): strand 16, helix 9, splice variant 2, propeptide 1, chain 1, active site 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

showing 30 of 166 structures by resolution:

PDB	Title	Method	Resolution (Å)
5LE5	Native human 20S proteasome at 1.8 Angstrom	X-RAY DIFFRACTION	1.8
5LEY	Human 20S proteasome complex with Oprozomib at 1.9 Angstrom	X-RAY DIFFRACTION	1.9
5LF4	Human 20S proteasome complex with Delanzomib at 2.0 Angstrom	X-RAY DIFFRACTION	1.99
5LF1	Human 20S proteasome complex with Dihydroeponemycin at 2.0 Angstrom	X-RAY DIFFRACTION	2
5LF7	Human 20S proteasome complex with Ixazomib at 2.0 Angstrom	X-RAY DIFFRACTION	2
8UD9	Structure of human constitutive 20S proteasome complexed with the inhibitor TDI-8304	ELECTRON MICROSCOPY	2.04
5LF6	Human 20S proteasome complex with Z-LLY-ketoaldehyde at 2.1 Angstrom	X-RAY DIFFRACTION	2.07
5LF3	Human 20S proteasome complex with Bortezomib at 2.1 Angstrom	X-RAY DIFFRACTION	2.1
8BZL	Human 20S Proteasome in complex with peptide activator peptide BLM42	X-RAY DIFFRACTION	2.14
5LEZ	Human 20S proteasome complex with Oprozomib in Mg-Acetate at 2.2 Angstrom	X-RAY DIFFRACTION	2.19
5LEX	Native human 20S proteasome in Mg-Acetate at 2.2 Angstrom	X-RAY DIFFRACTION	2.2
5LF0	Human 20S proteasome complex with Epoxomicin at 2.4 Angstrom	X-RAY DIFFRACTION	2.41
9K53	Structure of substrate-engaged human 26S proteasome RP-CP subcomplex in state ED2.1	ELECTRON MICROSCOPY	2.5
9HMN	CryoEM structure of human 20S proteasome in complex with proteasome inhibitor …	ELECTRON MICROSCOPY	2.55
4R3O	Human Constitutive 20S Proteasome	X-RAY DIFFRACTION	2.6
6HTR	Yeast 20S proteasome with human beta2c (S171G) in complex with 13	X-RAY DIFFRACTION	2.6
6RGQ	Human 20S Proteasome	ELECTRON MICROSCOPY	2.6
9YUZ	Structure of the human 20S proteasome in complex with a beta5-selective covalent …	ELECTRON MICROSCOPY	2.6
8QYL	Human 20S proteasome assembly intermediate structure 2	ELECTRON MICROSCOPY	2.67
6HTB	Yeast 20S proteasome with human beta2c (S171G)	X-RAY DIFFRACTION	2.7
8CVR	Human 20S proteasome with MG-132	ELECTRON MICROSCOPY	2.7
6KWY	human PA200-20S complex	ELECTRON MICROSCOPY	2.72
8QYJ	Human 20S proteasome assembly structure 1	ELECTRON MICROSCOPY	2.73
8QYM	Human 20S proteasome assembly intermediate structure 3	ELECTRON MICROSCOPY	2.73
8USB	Non-substrate-engaged human 26S proteasome with Nub1/FAT10 bound to Rpn1	ELECTRON MICROSCOPY	2.73
9MBP	Substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral …	ELECTRON MICROSCOPY	2.75
6HTC	Yeast 20S proteasome with human beta2c (S171G) in complex with ONX 0914	X-RAY DIFFRACTION	2.8
6HUU	Yeast 20S proteasome with human beta2c (S171G) in complex with 29	X-RAY DIFFRACTION	2.8
7NAN	Human 20S proteasome core particle	ELECTRON MICROSCOPY	2.8
8TM6	Human premature 20S proteasome assembly intermediate	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99436-F1	90.42	0.73

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Threonine-type peptidases, Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; nuclear bodies; primary cilium

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
44	nucleophile

Function

Pathways and Gene Ontology

Reactome pathways

59 curated (TAS) of 173; 13 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 173 pathways:

ID	Pathway	Evidence
R-HSA-5678895	Defective CFTR causes cystic fibrosis ⚕	curated
R-HSA-5362768	Hh mutants are degraded by ERAD ⚕	curated
R-HSA-180585	Vif-mediated degradation of APOBEC3G ⚕	curated
R-HSA-180534	Vpu mediated degradation of CD4 ⚕	curated
R-HSA-382556	ABC-family protein mediated transport	curated
R-HSA-9931269	AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	curated
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin	curated
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	curated
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA	curated
R-HSA-1169091	Activation of NF-kappaB in B cells	curated
R-HSA-9912633	Antigen processing: Ub, ATP-independent proteasomal degradation	curated
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	curated
R-HSA-68867	Assembly of the pre-replicative complex	curated
R-HSA-4608870	Asymmetric localization of PCP proteins	curated
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C	curated
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1	curated
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6	curated
R-HSA-5607764	CLEC7A (Dectin-1) signaling	curated
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A	curated
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)	curated
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling	curated
R-HSA-4641257	Degradation of AXIN	curated
R-HSA-9766229	Degradation of CDH1	curated
R-HSA-4641258	Degradation of DVL	curated
R-HSA-5610780	Degradation of GLI1 by the proteasome	curated
R-HSA-195253	Degradation of beta-catenin by the destruction complex	curated
R-HSA-202424	Downstream TCR signaling	curated
R-HSA-8854050	FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	curated
R-HSA-2871837	FCERI mediated NF-kB activation	curated
R-HSA-69481	G2/M Checkpoints	curated
R-HSA-5610785	GLI3 is processed to GLI3R by the proteasome	curated
R-HSA-9762114	GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	curated
R-HSA-9929356	GSK3B-mediated proteasomal degradation of PD-L1(CD274)	curated
R-HSA-5632684	Hedgehog ‘on’ state	curated
R-HSA-5358346	Hedgehog ligand biogenesis	curated
R-HSA-9020702	Interleukin-1 signaling	curated
R-HSA-9755511	KEAP1-NFE2L2 pathway	curated
R-HSA-5687128	MAPK6/MAPK4 signaling	curated
R-HSA-5676590	NIK–>noncanonical NF-kB signaling	curated
R-HSA-8951664	Neddylation	curated
R-HSA-9974237	Negative Regulation of DNA Double Strand Break Response	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-68949	Orc1 removal from chromatin	curated
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	curated
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs	curated
R-HSA-8948751	Regulation of PTEN stability and activity	curated
R-HSA-5658442	Regulation of RAS by GAPs	curated
R-HSA-8941858	Regulation of RUNX3 expression and activity	curated
R-HSA-350562	Regulation of ornithine decarboxylase (ODC)	curated
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21	curated
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1	curated
R-HSA-9929491	SPOP-mediated proteasomal degradation of PD-L1(CD274)	curated
R-HSA-2467813	Separation of Sister Chromatids	curated
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway	curated
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint	curated
R-HSA-5689603	UCH proteinases	curated
R-HSA-5689880	Ub-specific processing proteases	curated
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	curated
R-HSA-75815	Ubiquitin-dependent degradation of Cyclin D	curated
R-HSA-5619084	ABC transporter disorders ⚕	—

MSigDB gene sets: 388 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, 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, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21

GO Biological Process (14): DNA repair (GO:0006281), apoptotic process (GO:0006915), DNA damage response (GO:0006974), response to oxidative stress (GO:0006979), spermatogenesis (GO:0007283), proteasomal protein catabolic process (GO:0010498), proteasomal ubiquitin-independent protein catabolic process (GO:0010499), flagellated sperm motility (GO:0030317), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), meiotic cell cycle (GO:0051321), regulation of proteasomal protein catabolic process (GO:0061136), cellular response to type I interferon (GO:0071357), regulation of G1/S transition of mitotic cell cycle (GO:2000045), proteolysis (GO:0006508)

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

GO Cellular Component (13): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome core complex (GO:0005839), synaptic vesicle (GO:0008021), nuclear body (GO:0016604), proteasome core complex, beta-subunit complex (GO:0019774), proteasome storage granule (GO:0034515), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

18 top-level categories:

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
Stabilization of p53	1
Metabolism of polyamines	1
Transport of small molecules	1

GO top-level categories

52 GO namespaces:

Category	Terms
cellular anatomical structure	4
proteasomal protein catabolic process	3
intracellular protein-containing complex	2
intracellular anatomical structure	2
cytoplasm	2
intracellular membraneless organelle	2
DNA metabolic process	1
DNA damage response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
response to stress	1
developmental process involved in reproduction	1
male gamete generation	1
protein catabolic process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
ubiquitin-dependent protein catabolic process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
regulation of protein catabolic process	1
response to type I interferon	1
cellular response to cytokine stimulus	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
protein metabolic process	1
peptidase activity	1
endopeptidase activity	1
threonine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
proteasome complex	1
catalytic complex	1
exocytic vesicle	1
presynapse	1
nucleoplasm	1
proteasome core complex	1
protein-containing complex	1
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 33 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
proteasomal protein catabolic process	BP	direct assay
proteasome-mediated ubiquitin-dependent protein catabolic process	BP	direct assay
regulation of proteasomal protein catabolic process	BP	direct assay
response to oxidative stress	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nuclear body	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
proteasome complex	CC	direct assay
proteasome core complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,598 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB7	PSMB2	P31145	838
PSMB7	PSMB6	P28072	801
PSMB7	PSMB5	P28074	786
PSMB7	PSMB1	P20618	712
PSMB7	PSMB3	P31147	709
PSMB7	PSMA1	P25786	693
PSMB7	PSMB4	P28070	682
PSMB7	PSMA5	P28066	663
PSMB7	PSMA4	P25789	662
PSMB7	PSMA6	P34062	660
PSMB7	PSMA3	P25788	644
PSMB7	PSME3	P61289	631
PSMB7	PSMD1	Q99460	617
PSMB7	PSMC2	P35998	610
PSMB7	PSMC1	P49014	604

IntAct

Human interaction partners of PSMB7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

Partner	Interaction type	MIscore	Records
POMP	physical association	0.910	2
PSMB1	association	0.900	8
PSMB5	physical association	0.890	2
PSMB3	physical association	0.840	1
PSMB9	physical association	0.840	1
PSMB6	physical association	0.800	2
PSMB4	physical association	0.800	1
PSMA7	association	0.790	3
PSMA4	association	0.790	1
PSMD11	association	0.640	2
PSMD4	physical association	0.560	1
PSMD12	association	0.530	1
HTT	physical association	0.400	1
PSMB8	physical association	0.370	2
AFP	physical association	0.370	1
FUS	physical association	0.370	1
PSMD1	association	0.350	1
EIF1B	physical association	0.000	1
EMG1	physical association	0.000	1
EPB41	physical association	0.000	1
PAK2	physical association	0.000	1
PSMD6	physical association	0.000	1

BioGRID (541 interactions; top human partners by supporting records): PSMB1 (Affinity Capture-MS; 26 records), PSMB4 (Affinity Capture-MS; 20 records), PSMA2 (Affinity Capture-MS; 17 records), PSMA4 (Affinity Capture-MS; 15 records), PSMB3 (Affinity Capture-MS; 15 records), PSMB6 (Affinity Capture-MS; 12 records), PSMB5 (Affinity Capture-MS; 11 records), PSMA1 (Affinity Capture-MS; 10 records), PSMB2 (Affinity Capture-MS; 10 records), PSMA5 (Affinity Capture-MS; 9 records), PSMA6 (Affinity Capture-MS; 9 records), PSMA7 (Affinity Capture-MS; 9 records), POMP (Affinity Capture-MS; 8 records), PSMA3 (Affinity Capture-MS; 8 records), PSMB8 (Co-fractionation; 7 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PSMB7	“form complex”	“26S Proteasome”	binding

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ PA700-20S-PA28 complex	36	PSMA5, PSMD4, PSMD6, PSMD9, PSME1, PSME2, PSMD11, PSMB1, PSMB4, PSMC1, PSMA3, PSMB5, PSMD10, PSMA7, PSMC5, PSMD14, PSMD7, PSMA6, PSMB6, PSMD12, PSMD3, PSMD1, PSMA4, PSMB7, PSMC3, PSMC4, PSMC6, PSMD8, PSMB3, PSMC2, PSMD13, PSMA1, PSMA2, PSMB2, PSMD2, PSMD5
★ 26S proteasome	22	PSMA2, PSMA7, PSMB3, PSMA5, PSMA6, PSMB4, PSMB7, PSMC1, PSMC2, PSMC5, PSMC6, PSMA3, PSMB2, PSMB5, PSMC3, PSMC4, PSMD13, PSMD4, PSMA1, PSMA4, PSMB1, PSMB6
★ PA28-20S proteasome	16	PSMA6, PSMB5, PSMA2, PSMA7, PSMB2, PSMB4, PSME1, PSMA3, PSMB1, PSMB3, PSMB6, PSME2, PSMA1, PSMA5, PSMB7, PSMA4
★ PA28gamma-20S proteasome	15	PSMB5, PSMA5, PSMB1, PSMB4, PSME3, PSMA1, PSMA4, PSMA7, PSMB2, PSMA2, PSMA3, PSMB6, PSMB7, PSMA6, PSMB3
★ 20S proteasome	14	PSMA5, PSMA6, PSMB1, PSMB6, PSMA2, PSMA7, PSMB2, PSMB3, PSMB4, PSMB5, PSMB7, PSMA1, PSMA3, PSMA4

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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	9	244.7×	2e-20
Regulation of activated PAK-2p34 by proteasome mediated degradation	12	159.2×	8e-24
Cross-presentation of soluble exogenous antigens (endosomes)	13	157.1×	9e-26
Proteasome assembly	15	145.7×	2e-29
Regulation of ornithine decarboxylase (ODC)	11	142.4×	3e-21
Vpu mediated degradation of CD4	11	139.1×	3e-21
Autodegradation of the E3 ubiquitin ligase COP1	11	139.1×	3e-21
Ubiquitin-dependent degradation of Cyclin D	11	139.1×	3e-21

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	14	33.2×	2e-17

Disease & clinical

Genetic variants

Variant evidence for PSMB7: 16 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,127):

Position(s)	Effect	Δscore	Sites
9:124356762–124356763	donor_loss	1.0000	3
9:124356916–124356917	acceptor_loss	1.0000	4
9:124412350–124412351	donor_loss	1.0000	3
9:124413906–124413907	donor_loss	1.0000	2
9:124414006–124414007	acceptor_loss	1.0000	3
9:124414840–124414841	donor_loss	1.0000	4
9:124353710–124353711	acceptor_loss	0.9900	6
9:124356762–124356763	donor_loss	0.9900	2
9:124356916	acceptor_loss	0.9900
9:124384596–124384597	donor_loss	0.9900	5

AlphaMissense

922 missense substitutions predicted likely pathogenic (of 1,804 scored), across 204 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D60	8	0.998	0.999
D209	8	0.998	0.999
D94	8	0.997	0.999
D147	8	0.989	0.996
D217	8	0.982	0.992
H78	8	0.980	0.997
H159	8	0.945	0.984
F14	8	0.923	0.986
F181	8	0.922	0.992
F16	8	0.913	0.990
D71	8	0.912	0.975
D163	8	0.905	0.978
N22	8	0.903	0.988
M178	8	0.870	0.984
K76	7	0.993	1.000
F131	7	0.992	0.998
E182	7	0.988	0.997
C86	7	0.970	1.000
C87	7	0.967	1.000
F185	7	0.965	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.62e-06
Lung Adenocarcinoma (TCGA)	unfavorable	2.86e-05

Disease associations

OMIM: gene MIM:604030 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006061_27	Atrial fibrillation	7e-9

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3347256 (SINGLE PROTEIN), CHEMBL3831201 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,320 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL325041	BORTEZOMIB	4	13,415
CHEMBL451887	CARFILZOMIB	4	13,156
CHEMBL2141296	IXAZOMIB	3	6,376
CHEMBL371405	MARIZOMIB	3	7,520
CHEMBL2103884	OPROZOMIB	2	2,853

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

177 measured of 219 human assays (219 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Cinnabaramide G	IC50	0.6 nM
CHEMBL4102324	IC50	0.92 nM
CINNABARAMIDE A	IC50	1 nM
MARIZOMIB	IC50	1.3 nM
CHEMBL4460323	IC50	1.5 nM
Alpha-ketocarbonyl derivative	IC50	2 nM
(R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-6-carboxamido)propanamido)butylboronic acid	IC50	2.4 nM
CHEMBL4517600	IC50	2.4 nM
CHEMBL4587036	IC50	2.5 nM
CHEMBL4444107	IC50	3.4 nM
CHEMBL5197285	IC50	3.4 nM
CHEMBL6143686	IC50	3.4 nM
CHEMBL4541038	IC50	3.6 nM
CHEMBL4547405	IC50	3.9 nM
CHEMBL5171225	IC50	4 nM
CHEMBL4581126	IC50	4.3 nM
CHEMBL4542373	IC50	4.6 nM
CHEMBL4558648	IC50	4.6 nM
CHEMBL4467618	IC50	4.8 nM
CHEMBL5186240	IC50	5.2 nM
CHEMBL3237860	IC50	5.7 nM
Alpha-ketocarbonyl derivative	IC50	6 nM
Cinnabaramide F	IC50	6 nM
CHEMBL4447701	IC50	6.4 nM
CHEMBL4435814	IC50	6.4 nM
CHEMBL4436430	IC50	6.5 nM
CHEMBL432281	IC50	7 nM
CHEMBL5202627	IC50	7 nM
CHEMBL5208573	IC50	7.2 nM
CHEMBL3237874	IC50	7.7 nM
CHEMBL4559271	IC50	7.7 nM
CHEMBL5172645	IC50	8.1 nM
CHEMBL5179570	IC50	8.4 nM
CHEMBL5209077	IC50	8.6 nM
CHEMBL5173459	IC50	8.9 nM
CHEMBL5188065	IC50	9.3 nM
CHEMBL5196378	IC50	9.3 nM
CHEMBL4572638	IC50	9.4 nM
CHEMBL5201055	IC50	9.4 nM
CHEMBL4441018	IC50	9.5 nM
Cinnabaramide C	IC50	12 nM
TP-103	IC50	14 nM
CHEMBL4578081	IC50	14 nM
MLN2238	IC50	15 nM
CHEMBL4443333	IC50	15 nM
CHEMBL4864661	IC50	16 nM
CHEMBL4875208	IC50	16 nM
CHEMBL4557130	IC50	17 nM
CHEMBL27225	IC50	18 nM
TP-108	IC50	18 nM

ChEMBL bioactivities

315 potent at pChembl≥5 of 340 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

314 with measured affinity, of 1000 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
Bortezomib	2205591: Inhibition of 20S proteasome (unknown origin)	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
(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
4-methyl-N-[(2R)-1-[[(2R)-4-methyl-1-[(2S)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide	2236585: Activation of 26s proteosome (unknown origin)	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	4
sodium arsenite	affects binding, increases reaction, increases expression	3
bisphenol A	decreases expression	2
Vehicle Emissions	affects cotreatment, decreases expression, affects expression, increases reaction	2
Doxorubicin	increases expression, increases metabolic processing	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	affects expression, increases reaction	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment	1
salinomycin	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
cupric chloride	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
chloropicrin	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
stattic	decreases expression	1
bisphenol S	increases expression	1
EGFR tyrosine kinase inhibitor 324674	decreases reaction, increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

171 unique, capped per target: 162 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PSMB7 across ~30M SureChEMBL compounds — explore on Sugi Predict.