PSMB8

Summary

PSMB8 (proteasome 20S subunit beta 8, HGNC:9545) is a protein-coding gene on chromosome 6p21.32, encoding Proteasome subunit beta type-8 (P28062). 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 is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 3 (proteasome beta 5 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. Two alternative transcripts encoding two isoforms have been identified; both isoforms are processed to yield the same mature subunit.

Source: NCBI Gene 5696 — RefSeq curated summary.

At a glance

• Gene–disease (curated): proteasome-associated autoinflammatory syndrome 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 282 total — 16 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 80
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_148919

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9545
Approved symbol	PSMB8
Name	proteasome 20S subunit beta 8
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	RING10, D6S216E, PSMB5i, beta5i
Ensembl gene	ENSG00000204264
Ensembl biotype	protein_coding
OMIM	177046
Entrez	5696

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 retained_intron

ENST00000374881, ENST00000374882, ENST00000395339, ENST00000484003, ENST00000650411, ENST00000650793, ENST00000697612, ENST00000923626

RefSeq mRNA: 2 — MANE Select: NM_148919 NM_004159, NM_148919

CCDS: CCDS4756, CCDS4757

Canonical transcript exons

ENST00000374882 — 6 exons

Exon	Start	End
ENSE00001622641	32842672	32842783
ENSE00001663215	32842942	32843089
ENSE00001830775	32843850	32844047
ENSE00003512806	32841531	32841735
ENSE00003525872	32842134	32842263
ENSE00003903288	32840717	32841047

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.2960 / max 615.5481, expressed in 1735 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73026	41.6343	1690
73028	10.6497	1516
73031	3.4620	1154
73030	2.5253	799
73025	0.4878	191
73027	0.3074	135
73029	0.2295	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.16	gold quality
leukocyte	CL:0000738	98.60	gold quality
spleen	UBERON:0002106	98.57	gold quality
monocyte	CL:0000576	98.56	gold quality
lymph node	UBERON:0000029	98.56	gold quality
vermiform appendix	UBERON:0001154	98.29	gold quality
mucosa of transverse colon	UBERON:0004991	98.28	gold quality
duodenum	UBERON:0002114	98.07	gold quality
blood	UBERON:0000178	97.91	gold quality
rectum	UBERON:0001052	97.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.00	gold quality
right lung	UBERON:0002167	96.86	gold quality
upper lobe of left lung	UBERON:0008952	96.67	gold quality
small intestine	UBERON:0002108	96.63	gold quality
transverse colon	UBERON:0001157	96.52	gold quality
right adrenal gland	UBERON:0001233	96.42	gold quality
left adrenal gland	UBERON:0001234	96.34	gold quality
left adrenal gland cortex	UBERON:0035825	96.22	gold quality
gall bladder	UBERON:0002110	96.19	gold quality
smooth muscle tissue	UBERON:0001135	96.07	gold quality
bone marrow	UBERON:0002371	95.97	gold quality
skin of abdomen	UBERON:0001416	95.92	gold quality
right adrenal gland cortex	UBERON:0035827	95.86	gold quality
right lobe of liver	UBERON:0001114	95.77	gold quality
right uterine tube	UBERON:0001302	95.66	gold quality
zone of skin	UBERON:0000014	95.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.49	gold quality
metanephros cortex	UBERON:0010533	95.42	gold quality
adipose tissue	UBERON:0001013	95.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	38.13
E-CURD-46	yes	21.22
E-HCAD-1	yes	18.33
E-ANND-3	yes	10.43
E-GEOD-125970	no	6.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, FOXO1, PRDM1

miRNA regulators (miRDB)

9 targeting PSMB8, 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-3151-5P	99.86	63.83	1069
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-5009-5P	94.82	63.89	775
HSA-MIR-8058	94.76	63.41	632
HSA-MIR-451A	91.68	64.18	71

Literature-anchored findings (GeneRIF, showing 40)

• The frequencies of LMP7 genotypes and alleles showed no significant differences among different ages of diabetic onset. (PMID:11793848)
• Impaired expression of proteasome subunits is involved in the loss of HLA class I expression in human colon cancer cells. (PMID:12519221)
• LMP7 is associated with vitiligo. (PMID:14551602)
• interaction of TAP1 and TAP2 and P-glycoprotein with proteasome subunits beta-5 and beta-5i suggest direct targeting of antigenic peptides to the ER via a TAP-proteasome association and a possible role for P-glycoprotein (PMID:15488952)
• upregulation by IRF-1 and interferon gamma (PMID:15907481)
• Expression of LMP7E1 is cancer cells is an additional strategy of oncogenesis (PMID:16423992)
• two inducible subunits of the proteasome, lmp2 and lmp7, are transcriptionally up-regulated by heat shock; heat-shocked cells show enhanced presentation of immunoproteasome-dependent MHC I antigenic epitopes, but not immunoproteasome-independent epitopes (PMID:17142736)
• LMP7-145 site is associated with the risk of HBV infection. (PMID:17525827)
• study found strong associations of psoriasis with variant alleles of LMP and TAP (PMID:17581627)
• Patients with proteinuria greater than 0.5 g/1.73 m(2)/day had a significant switch of the chymotryptic-like beta5 protease to the LMP7 subunit, but this did not occur in patients with idiopathic nephrotic syndrome (PMID:19037255)
• The different proteasome profiles of (IFN)DC and (IL-4)DC were associated with a greater ability of (IFN)DC to present an immunodominant epitope that requires LMP7 expression for its processing. (PMID:19065646)
• Downregulation of LMP7 is associated with acute myeloid leukaemic blasts. (PMID:19148137)
• Interferon-induced PSMB8/LMP7 accelerates the degradation of Mcl-1 and increases the sensitivity of vascular lesion cells to apoptosis induced by fas ligation. (PMID:19443843)
• the immunoproteasome appears to be a key link between inflammatory factors and the control of vascular cell apoptosis and may thus be an important factor in plaque rupture and myocardial infarction. (PMID:19443843)
• LMP7 gene polymorphism showed identical frequency of different genotypes in hypertensive patients (Lys/Lys–92.4%, Lys/Gln–7.6%, Gln/Gln–0%) and healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). (PMID:19526842)
• the reduced LMP7-mRNA level by HSV-1 could be of biological importance, since the virus could escape/hide from immune system of the host and establish latency processes. (PMID:19619915)
• In a southern Spanish population, no differences were observed in the frequencies of the LMP and TAP genotypes between brucellosis patients and controls. (PMID:20470844)
• PSMB8 encodes a catalytic subunit of the 20S immunoproteasomes called beta5i. Immunoproteasome-mediated proteolysis generates immunogenic epitopes presented by major histocompatibility complex (MHC) class I molecules (PMID:21129723)
• the genetic variant within the LMP2/LMP7 gene would increase the risk of intestinal M. tuberculosis infection. (PMID:21303409)
• HLA-I, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%, 44%, 48%, 40%, 52%, 32% and 20% of esophageal squamous cell carcinoma lesions then, respectively. (PMID:21362330)
• In patients with primary Sjogren’s syndrome, the expression of LMP7 (but not LMP2) is up-regulated in the labial gland. (PMID:21529441)
• we identified two single nucleotide polymorphisms within the beta5i/LMP7-encoding gene sequences, which were in strong linkage disequilibrium, as independent genetic risk factors for type 1 diabetes development in humans (PMID:21804012)
• Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome (PMID:21852578)
• found a homozygous missense mutation (G197V) in immunoproteasome subunit, beta type 8 (PSMB8), which encodes one of the beta subunits induced by IFN-gamma in patients from 2 consanguineous families with lipodystrophy (PMID:21881205)
• CANDLE syndrome is caused by mutations in PSMB8, a gene recently reported to cause “JMP” syndrome in adults. (PMID:21953331)
• high risk of colon cancer was associated with LMP7-K/Q genotype and low risk with LMP7-Q/Q genotype; results suggest the presence of LMP7-K can reduce formation of immunoproteasomes and thus peptide processing, followed by reduced peptide-HLA presentation, a crucial factor in the immune response against cancer (PMID:22037870)
• The MAGE-C(2336-344) antigenic peptide is produced by the immunoproteasome and intermediate proteasome beta1i-beta5i, but not by the standard proteasome nor intermediate proteasome beta5i. (PMID:22925930)
• Data indicate that treatment-emergent resistance to single-agent bortezomib was independent of variants in the proteasome genes PSMB1, PSMB5, PSMB6, PSMB8, PSMB9, and PSMB10. (PMID:23018640)
• The LMP7 gene promoter methylation and protein downregulation were correlated at high extent in Kazakh’s ESCC patients, and may explain the epigenetic regulation on gene expression. (PMID:23283737)
• Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. (PMID:25098831)
• lupus nephritis showed up-regulation of the immunoproteasome subunit LMP7 in tubular epithelial cells associated with type I interferon signature. (PMID:25889472)
• We described a Brazilian patient with CANDLE syndrome possessing a novel mutation in the PSMB8 gene. (PMID:26567544)
• Upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. (PMID:26894977)
• designed siRNAs that efficiently silence LMP2, LMP7 and MECL-1 gene expression. (PMID:26944796)
• there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in Parkinson’s disease patients (PMID:27098790)
• Proteasome beta5i Subunit Deficiency Affects Opsonin Synthesis and Aggravates Pneumococcal Pneumonia. (PMID:27100179)
• Data show that tight junction protein 1 (TJP1) suppressed expression of the catalytically proteasome subunits LMP7 and LMP2, decreased proteasome activity, and enhanced proteasome inhibitor sensitivity in vitro and in vivo through suppression of EGFR/JAK1/STAT3 signaling. (PMID:27132469)
• demonstrated that patients with the LMP-7 CA/AA genotypes were more likely to have advanced fibrosis scores than those bearing the CC genotype (PMID:27156327)
• JAK1 mutations are highly frequent in microsatellite unstable endometrial cancer, not associated with survival, but are associated with impaired upregulation of LMP7 and HLA class I and may therefore facilitate immune escape (PMID:27213585)
• The results show that PSMB8 exon 2 SNP is significantly associated with vitiligo. (PMID:28207947)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb8a	ENSDARG00000001303
mus_musculus	Psmb8	ENSMUSG00000024338
rattus_norvegicus	Psmb8	ENSRNOG00000000456
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), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit beta type-8 — P28062 (reviewed: P28062)

Alternative names: Low molecular mass protein 7, Macropain subunit C13, Multicatalytic endopeptidase complex subunit C13, Proteasome component C13, Proteasome subunit beta-5i, Really interesting new gene 10 protein

All UniProt accessions (3): P28062, Q5JNW7, X5CMJ9

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. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein. Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes.

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. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB5. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Directly interacts with POMP. Interacts with TAP1. (Microbial infection) Interacts with HIV-1 TAT protein.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.

Disease relevance. Proteasome-associated autoinflammatory syndrome 1 (PRAAS1) [MIM:256040] An autosomal recessive autoinflammatory disorder characterized by early childhood onset of recurrent fever, joint stiffness and severe contractures of the hands and feet, and erythematous skin lesions with subsequent development of lipodystrophy and laboratory evidence of immune dysregulation. Accompanying features may include muscle weakness and atrophy, hepatosplenomegaly, and microcytic anemia. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by IFNG/IFN-gamma and IRF1 (at protein level). Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn’s bowel disease (CD). Down-regulated by the selective inhibitor PR-957. Down-regulated in mature dendritic cells by HSV-1 infection. Up-regulated by heat shock treatment.

Similarity. Belongs to the peptidase T1B family.

Isoforms (2)

UniProt ID	Names	Canonical?
P28062-1	1, LMP7B, LMP7-E2	yes
P28062-2	2, LMP7A, LMP7-E1

RefSeq proteins (2): NP_004150, NP_683720* (*=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 (33 total): strand 12, sequence variant 8, helix 5, propeptide 1, chain 1, region of interest 1, turn 1, active site 1, modified residue 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
7AWE	X-RAY DIFFRACTION	2.29
5L5A	X-RAY DIFFRACTION	2.4
7B12	X-RAY DIFFRACTION	2.43
5L5F	X-RAY DIFFRACTION	2.5
5L5H	X-RAY DIFFRACTION	2.6
5L5O	X-RAY DIFFRACTION	2.6
5L5S	X-RAY DIFFRACTION	2.6
5L5U	X-RAY DIFFRACTION	2.6
5L5V	X-RAY DIFFRACTION	2.7
5LTT	X-RAY DIFFRACTION	2.7
5M2B	X-RAY DIFFRACTION	2.7
6E5B	X-RAY DIFFRACTION	2.77
5L5B	X-RAY DIFFRACTION	2.8
5L5D	X-RAY DIFFRACTION	2.8
5L5P	X-RAY DIFFRACTION	2.8
5L5Q	X-RAY DIFFRACTION	2.8
5L5E	X-RAY DIFFRACTION	2.9
5L5I	X-RAY DIFFRACTION	2.9
5L5J	X-RAY DIFFRACTION	2.9
5L5R	X-RAY DIFFRACTION	2.9
5L5T	X-RAY DIFFRACTION	2.9
6AVO	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28062-F1	84.28	0.67

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 (2): 73 (nucleophile); 72–73 (cleavage; by autolysis)

Post-translational modifications (1): 5

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-9907900	Proteasome assembly
R-HSA-9912633	Antigen processing: Ub, ATP-independent proteasomal degradation

MSigDB gene sets: 598 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, WALLACE_PROSTATE_CANCER_RACE_UP, MODULE_169, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GOBP_T_CELL_HOMEOSTASIS, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOZGIT_ESR1_TARGETS_DN

GO Biological Process (7): antigen processing and presentation (GO:0019882), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), fat cell differentiation (GO:0045444), immune system process (GO:0002376), proteolysis (GO:0006508), cell differentiation (GO:0030154), obsolete proteolysis involved in protein catabolic process (GO:0051603)

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 (9): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome core complex (GO:0005839), proteasome core complex, beta-subunit complex (GO:0019774), extracellular exosome (GO:0070062), spermatoproteasome complex (GO:1990111), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
Interferon Signaling	1
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular protein-containing complex	2
proteasome complex	2
intracellular anatomical structure	2
immune system process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cell differentiation	1
biological_process	1
protein metabolic process	1
cellular developmental 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
cytoplasm	1
catalytic complex	1
proteasome core complex	1
protein-containing complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

2920 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB8	PSMB10	P40306	990
PSMB8	PSMB9	P28065	988
PSMB8	PSME2	Q9UL46	933
PSMB8	PSME1	Q06323	928
PSMB8	CTRL	P40313	918
PSMB8	POMP	Q9Y244	901
PSMB8	IFNG	P01579	883
PSMB8	TAPBP	O15533	855
PSMB8	TAP1	Q03518	834
PSMB8	HLA-DOB	P13765	832
PSMB8	TAP2	Q03519	812
PSMB8	SFMBT1	Q9UHJ3	778
PSMB8	PSMA1	P25786	739
PSMB8	PSMB1	P20618	738
PSMB8	PSMA8	Q8TAA3	728

IntAct

42 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:2364”(proximity)	0.950
PSMB7	PSMB1	psi-mi:“MI:0914”(association)	0.900
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PSMB8		psi-mi:“MI:0915”(physical association)	0.580
	PSMB8	psi-mi:“MI:0915”(physical association)	0.580
PSMB9	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMA5	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMB7	PSMD12	psi-mi:“MI:0914”(association)	0.530
PSMB8	PSMA2	psi-mi:“MI:0914”(association)	0.530
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMB8	TAP1	psi-mi:“MI:0915”(physical association)	0.370
PSMB8	TAP2	psi-mi:“MI:0915”(physical association)	0.370
LMP2	WWP2	psi-mi:“MI:0914”(association)	0.350
CFTR	MYH7B	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350
PSMB8	PSMA7	psi-mi:“MI:0914”(association)	0.350

BioGRID (226): HEATR1 (Co-fractionation), PSMA3 (Co-fractionation), PSMA4 (Co-fractionation), PSMB2 (Co-fractionation), PSMB3 (Co-fractionation), PSMB6 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation), PSMB8 (Co-fractionation)

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

Diamond homologs: A0B5B1, A0RXV1, A1RSJ8, A1RWY6, A1RX71, A1XQU1, A2BN24, A2BN27, A2SS78, A3CUS9, A3DN21, A3DN27, A3MXQ6, A4FYA5, A4WMZ0, A4YIE0, A5LHX3, A6VK02, A7I841, A7KE01, A7KII6, A8AA46, A8AB58, A8M8R5, A9A2U7, A9A788, B1L6S7, B1L6X8, B1YDJ0, B6YSW2, B6YXV3, B8GG66, C5A2D5, C7P6N4, C9REN7, D0KRX1, D0KTH0, D1Z199, D3S8M7, O23717

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
carfilzomib	“down-regulates activity”	PSMB8	“chemical inhibition”
PSMB8	“down-regulates quantity by destabilization”	MCL1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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	7	148.0×	4e-13
Cross-presentation of soluble exogenous antigens (endosomes)	9	84.6×	2e-14
Regulation of activated PAK-2p34 by proteasome mediated degradation	8	82.5×	6e-13
Regulation of ornithine decarboxylase (ODC)	8	80.6×	6e-13
Vpu mediated degradation of CD4	8	78.7×	6e-13
Autodegradation of the E3 ubiquitin ligase COP1	8	78.7×	6e-13
Ubiquitin-dependent degradation of Cyclin D	8	78.7×	6e-13
Proteasome assembly	10	75.5×	3e-15

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	12	18.4×	1e-10

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	4
Uncertain significance	121
Likely benign	84
Benign	18

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
2768840	NM_148919.4(PSMB8):c.227_230dup (p.Phe78fs)	Pathogenic
2818532	NM_148919.4(PSMB8):c.108_118del (p.Met37fs)	Pathogenic
2844110	NM_148919.4(PSMB8):c.383del (p.Glu128fs)	Pathogenic
2860423	NM_148919.4(PSMB8):c.50C>A (p.Ser17Ter)	Pathogenic
29860	NM_148919.4(PSMB8):c.602G>T (p.Gly201Val)	Pathogenic
3220940	NM_148919.4(PSMB8):c.163C>T (p.Gln55Ter)	Pathogenic
3220941	NM_148919.4(PSMB8):c.352T>C (p.Ser118Pro)	Pathogenic
3641579	NM_148919.4(PSMB8):c.337del (p.Leu113fs)	Pathogenic
3645559	NM_148919.4(PSMB8):c.21C>A (p.Cys7Ter)	Pathogenic
3672941	NM_148919.4(PSMB8):c.636_643del (p.Asp212fs)	Pathogenic
3712361	NM_148919.4(PSMB8):c.31C>T (p.Arg11Ter)	Pathogenic
3712942	NM_148919.4(PSMB8):c.434del (p.Arg145fs)	Pathogenic
548954	NM_148919.4(PSMB8):c.313A>C (p.Lys105Gln)	Pathogenic
659832	NM_148919.4(PSMB8):c.224C>T (p.Thr75Met)	Pathogenic
933294	NM_148919.4(PSMB8):c.608_611dup (p.Asn204fs)	Pathogenic
952176	NM_148919.4(PSMB8):c.421C>T (p.Arg141Ter)	Pathogenic
2027149	NM_148919.4(PSMB8):c.69_147+42del	Likely pathogenic
3064774	NM_004159.5(PSMB8):c.107_108del (p.Pro36fs)	Likely pathogenic
3246001	NC_000006.11:g.(?32810848)(32811339_?)del	Likely pathogenic
4797186	NM_148919.4(PSMB8):c.147+1G>T	Likely pathogenic

SpliceAI

771 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32841529:A:AC	donor_gain	1.0000
6:32841530:C:CC	donor_gain	1.0000
6:32841530:CT:C	donor_gain	1.0000
6:32841530:CTA:C	donor_gain	1.0000
6:32841600:AGG:A	donor_gain	1.0000
6:32841685:ATTT:A	donor_gain	1.0000
6:32841688:T:TA	donor_gain	1.0000
6:32841734:CC:C	acceptor_gain	1.0000
6:32841735:CC:C	acceptor_gain	1.0000
6:32842129:CCCA:C	donor_loss	1.0000
6:32842131:CACCT:C	donor_loss	1.0000
6:32842133:CCTT:C	donor_gain	1.0000
6:32842189:TGG:T	donor_gain	1.0000
6:32842259:ACAGC:A	acceptor_gain	1.0000
6:32842260:CAGC:C	acceptor_gain	1.0000
6:32842260:CAGCC:C	acceptor_gain	1.0000
6:32842261:AGC:A	acceptor_gain	1.0000
6:32842261:AGCC:A	acceptor_loss	1.0000
6:32842262:GC:G	acceptor_gain	1.0000
6:32842263:CC:C	acceptor_gain	1.0000
6:32842263:CCTGG:C	acceptor_loss	1.0000
6:32842264:C:CC	acceptor_gain	1.0000
6:32842264:CT:C	acceptor_loss	1.0000
6:32842265:T:G	acceptor_loss	1.0000
6:32842268:G:C	acceptor_gain	1.0000
6:32842268:G:GC	acceptor_gain	1.0000
6:32842275:C:CT	acceptor_gain	1.0000
6:32842276:A:T	acceptor_gain	1.0000
6:32842667:CTTA:C	donor_loss	1.0000
6:32842668:TTAC:T	donor_loss	1.0000

AlphaMissense

1786 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32842216:G:A	S152F	0.996
6:32842219:G:T	A151D	0.995
6:32842216:G:T	S152Y	0.994
6:32842997:G:C	F80L	0.992
6:32842997:G:T	F80L	0.992
6:32842999:A:G	F80L	0.992
6:32841653:G:T	A207D	0.991
6:32842147:C:T	G175D	0.991
6:32842158:A:C	S171R	0.991
6:32842158:A:T	S171R	0.991
6:32842160:T:G	S171R	0.991
6:32842693:C:G	R129P	0.991
6:32842700:A:G	W127R	0.991
6:32842700:A:T	W127R	0.991
6:32842969:A:G	S90P	0.991
6:32841045:A:C	Y249D	0.990
6:32841590:C:T	G228D	0.990
6:32842210:A:G	L154P	0.990
6:32842741:A:G	L113P	0.990
6:32842687:A:G	L131P	0.989
6:32841024:A:G	W256R	0.988
6:32841024:A:T	W256R	0.988
6:32841581:G:T	A231D	0.988
6:32841582:C:G	A231P	0.988
6:32843004:A:G	F78S	0.988
6:32841548:G:A	S242F	0.987
6:32841569:G:T	A235D	0.987
6:32842217:A:G	S152P	0.987
6:32842220:C:G	A151P	0.987
6:32842735:C:T	G115D	0.987

dbSNP variants (sampled 300 via entrez): RS1000381110 (6:32843691 C>A,G), RS1000989358 (6:32842062 T>C), RS1001653737 (6:32844953 A>G), RS1002655422 (6:32841471 ACC>A,AC,ACCC,ACCCC,ACCCCC,ACCCCCC), RS1003272544 (6:32846099 A>C), RS1003289311 (6:32846364 A>G), RS1003421442 (6:32840325 G>A,T), RS1003907769 (6:32845882 G>A,C), RS1004916318 (6:32844609 C>A,T), RS1007524117 (6:32843056 C>T), RS1008140191 (6:32845456 A>G), RS1009865824 (6:32843866 A>G,T), RS1010001049 (6:32844108 G>T), RS1010545572 (6:32841708 G>A), RS1010592599 (6:32840374 G>A)

Disease associations

OMIM: gene MIM:177046 | disease phenotypes: MIM:256040, MIM:604571

GenCC curated gene-disease

Disease	Classification	Inheritance
proteasome-associated autoinflammatory syndrome 1	Definitive	Autosomal recessive
proteosome-associated autoinflammatory syndrome	Strong	Autosomal dominant

Mondo (4): proteosome-associated autoinflammatory syndrome (MONDO:0009726), proteasome-associated autoinflammatory syndrome 1 (MONDO:0054698), autoinflammatory syndrome (MONDO:0019751), MHC class I deficiency (MONDO:0011476)

Orphanet (6): Proteasome-associated autoinflammatory syndrome (Orphanet:324977), Nakajo-Nishimura syndrome (Orphanet:2615), JMP syndrome (Orphanet:324999), CANDLE syndrome (Orphanet:325004), Autoinflammatory syndrome (Orphanet:93665), Immunodeficiency by defective expression of MHC class I (Orphanet:34592)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000031	Epididymitis
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000292	Loss of facial adipose tissue
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000448	Prominent nose
HP:0000509	Conjunctivitis
HP:0000520	Proptosis
HP:0000771	Gynecomastia
HP:0000858	Irregular menstruation
HP:0000882	Hypoplastic scapulae
HP:0000953	Hyperpigmentation of the skin
HP:0000956	Acanthosis nigricans
HP:0000998	Hypertrichosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001507	Growth abnormality
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001538	Protuberant abdomen
HP:0001635	Congestive heart failure
HP:0001640	Cardiomegaly
HP:0001744	Splenomegaly
HP:0001822	Hallux valgus

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001009_2	Nephropathy	2.000000e-12
GCST002655_18	IgA nephropathy	2.000000e-09
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_150	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST008916_27	Asthma	5.000000e-31
GCST008916_90	Asthma	4.000000e-15
GCST011781_8	IgA nephropathy	1.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538334	Nakajo syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831201 (PROTEIN COMPLEX GROUP), CHEMBL5620 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,732 (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
CHEMBL270515	DELANZOMIB	2	1,883
CHEMBL4297468	ZETOMIPZOMIB	2	129

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2071543	PSMB8, TAP1, TAP2		0.00	0
rs9357155	PSMB8, TAP2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — T1: Proteasome

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
zetomipzomib	Inhibition	7.41	pIC50
ONX-0914	Inhibition	7.0	pIC50
HT1042	Inhibition	6.38	pKi

Binding affinities (BindingDB)

94 measured of 136 human assays (136 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[(1R)-1-[[2-[(3,5-dichloro-2-pyridinyl)oxy]acetyl]amino]-2-phenylethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[(2-phenoxyacetyl)amino]-2-phenylethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(4-methylphenyl)-1-(3-phenoxypropanoylamino)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[3-(4-methoxyphenoxy)propanoylamino]-2-(4-methylphenyl)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyridin-3-ylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(4-cyanophenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(4-methoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyridin-3-yloxyacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(6-methoxy-2-pyridinyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(5-ethoxy-2-pyridinyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(3-methoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyrazin-2-ylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyrimidin-2-ylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(3,4,5-trifluorophenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[[2-(4-acetamidophenyl)acetyl]amino]-2-(1-benzofuran-3-yl)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2-methoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(4-ethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[3-(3-hydroxypropoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[[2-(3-acetamidophenyl)acetyl]amino]-2-(1-benzofuran-3-yl)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(2-hydroxyethoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(3-hydroxypropoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[3-(2-hydroxyethoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[3-(methoxymethyl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(3,4,5-trimethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[2-(oxan-4-yloxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2,5-dimethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2R)-3-hydroxy-2-phenylpropanoyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2,3,4-trimethoxyphenyl)acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(2-oxopyrrolidin-1-yl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[4-(2-hydroxypropan-2-yl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(7-methoxy-1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(7-fluoro-1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-[(3S)-2,3-dihydro-1-benzofuran-3-yl]-1-(3-phenoxypropanoylamino)ethyl]boronic acid	IC50	275 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
CHEMBL4786861	IC50	1360 nM
[(1R)-2-phenyl-1-[(2-pyridin-2-yloxyacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(4-methylphenyl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-2-(4-methylphenyl)ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyridin-4-ylacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[(2,2-difluoro-2-phenylacetyl)amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[2-(trifluoromethyl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-(2,6-dichlorophenyl)acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[2-[2-(trifluoromethoxy)phenyl]acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2S)-2-methoxy-2-phenylacetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2R)-2-methoxy-2-phenylacetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(2,4-dimethylphenyl)-1-[[2-(2,6-dimethylphenyl)acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2S)-2-phenylpropanoyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-1-[[2-(4-acetamidophenyl)acetyl]amino]-2-(2,4-dimethylphenyl)ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(2,4-dimethylphenyl)-1-[[2-[4-(2-oxopyrrolidin-1-yl)phenyl]acetyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors
[(1R)-2-(1-benzofuran-3-yl)-1-[[(2R)-2-phenylpropanoyl]amino]ethyl]boronic acid	IC50	2750 nM	US-10294246: Substituted boronic acids and boronate esters as immunoproteasome inhibitors

ChEMBL bioactivities

804 potent at pChembl≥5 of 908 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.40	IC50	0.4	nM	CHEMBL4751044
9.40	IC50	0.4	nM	CHEMBL4784875
9.22	IC50	0.6	nM	CINNABARAMIDE G
9.22	Ki	0.6	nM	CHEMBL5624541
9.22	Ki	0.6	nM	BORTEZOMIB
9.10	IC50	0.8	nM	CHEMBL4741140
9.04	IC50	0.92	nM	CHEMBL4102324
9.03	IC50	0.94	nM	CHEMBL5175132
9.00	IC50	1	nM	CINNABARAMIDE A
8.97	IC50	1.07	nM	CHEMBL5180795
8.96	IC50	1.1	nM	CHEMBL3218837
8.93	IC50	1.17	nM	CHEMBL5201806
8.92	IC50	1.2	nM	CHEMBL3319587
8.92	IC50	1.2	nM	CHEMBL4796570
8.89	IC50	1.3	nM	CHEMBL4749207
8.89	IC50	1.3	nM	MARIZOMIB
8.89	IC50	1.3	nM	BORTEZOMIB
8.85	IC50	1.4	nM	CHEMBL3319585
8.82	IC50	1.5	nM	CHEMBL4460323
8.82	IC50	1.5	nM	CHEMBL4764897
8.80	IC50	1.6	nM	CHEMBL4758484
8.77	IC50	1.7	nM	CHEMBL5188533
8.76	IC50	1.74	nM	CHEMBL5202276
8.74	IC50	1.8	nM	CHEMBL5192498
8.72	IC50	1.9	nM	CHEMBL5174892
8.72	IC50	1.9	nM	CHEMBL5191857
8.70	IC50	2	nM	CHEMBL3319478
8.70	IC50	2	nM	BORTEZOMIB
8.70	IC50	1.99	nM	CHEMBL5181060
8.70	IC50	2	nM	CHEMBL307387
8.68	IC50	2.1	nM	CHEMBL3319586
8.68	IC50	2.1	nM	CHEMBL5175217
8.66	IC50	2.2	nM	CHEMBL5185591
8.66	IC50	2.2	nM	CHEMBL5419917
8.64	IC50	2.3	nM	CHEMBL4784015
8.64	IC50	2.3	nM	CHEMBL5190088
8.64	IC50	2.3	nM	CHEMBL5170541
8.62	IC50	2.4	nM	CHEMBL4517600
8.62	IC50	2.4	nM	CHEMBL4763116
8.62	IC50	2.4	nM	BORTEZOMIB
8.62	IC50	2.4	nM	CHEMBL5413513
8.60	IC50	2.5	nM	CHEMBL3319482
8.60	IC50	2.5	nM	CHEMBL4587036
8.59	IC50	2.56	nM	BORTEZOMIB
8.59	IC50	2.59	nM	CHEMBL5207139
8.57	IC50	2.7	nM	CHEMBL3237863
8.57	IC50	2.7	nM	CHEMBL5394365
8.54	IC50	2.9	nM	CHEMBL5171825
8.54	IC50	2.9	nM	CHEMBL5203216
8.54	IC50	2.86	nM	CHEMBL5205273

PubChem BioAssay actives

772 with measured affinity, of 1728 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
(2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide	1604187: Inhibition of 20S proteasome beta 5i (unknown origin) after 1 hr by fluorescence based assay	ic50	<0.0001	uM
(2S)-N’-tert-butyl-2-[(4-methylphenyl)sulfonylamino]-N-[(2S)-1-(naphthalen-1-ylmethylamino)-1-oxopropan-2-yl]pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	ic50	0.0004	uM
(2S)-N’-tert-butyl-N-[(2S)-1-[(4-fluoronaphthalen-1-yl)methylamino]-3-methoxy-1-oxopropan-2-yl]-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	ic50	0.0004	uM
methyl (2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoate	277357: Inhibition of human 20S proteasome	ic50	0.0006	uM
[(1R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-(pyrazine-2-carbonyl)amino]-3-methylbutyl]boronic acid	2131634: Binding affinity to 20s proteosome (unknown origin) assessed as inhibition constant	ki	0.0006	uM
(2S)-N’-tert-butyl-N-[(2S)-1-[(4-fluoronaphthalen-1-yl)methylamino]-3-methoxy-1-oxopropan-2-yl]-2-[(4-methylphenyl)sulfonylamino]pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	ic50	0.0008	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	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
(2S)-N’-tert-butyl-2-[[(2S)-3-[(2-chloroacetyl)amino]-2-[(4-methylphenyl)sulfonylamino]propanoyl]amino]-N-[(2S)-1-[(4-methylphenyl)methylamino]-1-oxo-3-phenylpropan-2-yl]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	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
(2S)-N’-tert-butyl-2-[3-[(2-chloroacetyl)amino]propanoylamino]-N-[(2S)-3-naphthalen-2-yl-1-(naphthalen-1-ylmethylamino)-1-oxopropan-2-yl]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	ic50	0.0011	uM
(2S)-N-[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-3-pyridin-4-ylpropan-2-yl]-N’-(2,2-dimethylpropyl)-2-[[2-(1H-indol-3-yl)-2-oxoacetyl]amino]butanediamide	1683225: Inhibition of 20S immunoproteasome beta 5i subunit in human peripheral blood monocyte using Ac-ANW-AMC as substrate in presence of PA28alpha by fluorimetry analysis	ic50	0.0011	uM
(2S)-3-(4-methoxyphenyl)-N-[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-2-[[(2R)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide	1182706: Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry	ic50	0.0012	uM
(2S)-N’-tert-butyl-N-[(2S)-1-[(4-fluoronaphthalen-1-yl)methylamino]-1-oxopropan-2-yl]-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	ic50	0.0012	uM
(2S)-N’-tert-butyl-2-[[(2S)-3-[(2-chloroacetyl)amino]-2-(4-phenylbutanoylamino)propanoyl]amino]-N-[(2S)-1-[(4-methylphenyl)methylamino]-1-oxo-3-phenylpropan-2-yl]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	ic50	0.0012	uM
(1R,4R,5S)-4-(2-chloroethyl)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	1853759: Inhibition of 20S proteasome (unknown origin) by fluorescence based assay	ic50	0.0013	uM
[(1R)-1-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1687110: Inhibition of human 20S immunoproteasome beta 5 subunit chymotrypsin-like activity using fluorogenic peptide Ac-WLA-AMC as substrate in presence of PA28alpha incubated for 1 to 2 hrs by fluorescence microplate reader assay	ic50	0.0013	uM
Bortezomib	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0013	uM
N-[(2S)-1-[[(2S)-3-(4-methoxyphenyl)-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methyl-1H-indene-2-carboxamide	1182706: Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry	ic50	0.0014	uM
(2S)-N’-tert-butyl-N-[(2S)-1-(naphthalen-1-ylmethylamino)-1-oxopropan-2-yl]-2-(3-phenylpropanoylamino)pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	ic50	0.0015	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0015	uM
(2S)-N’-tert-butyl-N-[(2S)-1-[(4-fluoronaphthalen-1-yl)methylamino]-1-oxopropan-2-yl]-2-(3-phenylpropanoylamino)pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	ic50	0.0016	uM
[(1R)-2-(3-ethylphenyl)-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0017	uM
(2S)-N’-tert-butyl-2-[3-[[(E)-3-(4-chlorophenyl)-2-cyanoprop-2-enoyl]amino]propanoylamino]-N-[(2S)-3-naphthalen-2-yl-1-(naphthalen-1-ylmethylamino)-1-oxopropan-2-yl]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	ic50	0.0017	uM
[(1R)-2-[(3S)-7-chloro-2,3-dihydro-1-benzofuran-3-yl]-1-[(2-phenylacetyl)amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0018	uM
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyrazin-2-ylacetyl)amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0019	uM
[(1R)-2-(1-benzofuran-3-yl)-1-(3-methoxypropanoylamino)ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0019	uM
(2S)-3-(4-methoxyphenyl)-N-[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide	1182706: Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry	ic50	0.0020	uM
(2S)-N’-tert-butyl-2-[[(2S)-3-[(2-chloroacetyl)amino]-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]propanoyl]amino]-N-[(2S)-1-[(4-methylphenyl)methylamino]-1-oxo-3-phenylpropan-2-yl]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	ic50	0.0020	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
(2S)-3-(1H-indol-3-yl)-N-[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-2-[[(2R)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide	1182706: Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry	ic50	0.0021	uM
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0021	uM
[(1R)-2-(7-methoxy-1-benzofuran-3-yl)-1-[(2-phenylacetyl)amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0022	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
(2S)-N’-tert-butyl-N-[(2S)-3-methoxy-1-(naphthalen-1-ylmethylamino)-1-oxopropan-2-yl]-2-(3-phenylpropanoylamino)pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	ic50	0.0023	uM
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyrimidin-2-ylacetyl)amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0023	uM
[(1R)-2-(1-benzofuran-3-yl)-1-[(2-pyridin-3-ylacetyl)amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0023	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
(2S)-N’-tert-butyl-N-[(2S)-1-[(4-fluoronaphthalen-1-yl)methylamino]-1-oxopropan-2-yl]-2-[(4-methylphenyl)sulfonylamino]pentanediamide	1699438: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity	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
N-[(2R)-1-[[(2S)-3-(1H-indol-3-yl)-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methyl-1H-indene-2-carboxamide	1182706: Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry	ic50	0.0025	uM
(2S)-N’-tert-butyl-N-[(2S)-1-(naphthalen-1-ylmethylamino)-1-oxo-3-phenylpropan-2-yl]-2-[3-(propanoylamino)propanoylamino]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	ic50	0.0026	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
[(1R)-2-[(3S)-7-chloro-2,3-dihydro-1-benzofuran-3-yl]-1-[[2-(2-cyanophenyl)acetyl]amino]ethyl]boronic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0029	uM
[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid;2-hydroxypropane-1,2,3-tricarboxylic acid	1895437: Inhibition of human 20S immunoproteasome beta-5i subunit using Suc-LLVY-AMC as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0029	uM
(2S)-N’-tert-butyl-2-[3-[[(E)-2-cyano-3-(furan-2-yl)prop-2-enoyl]amino]propanoylamino]-N-[(2S)-1-[(4-methylphenyl)methylamino]-1-oxo-3-phenylpropan-2-yl]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	ic50	0.0029	uM
(2S)-N’-tert-butyl-2-[[(2S)-3-[(2-chloroacetyl)amino]-2-[[2-(1H-indol-3-yl)-2-oxoacetyl]amino]propanoyl]amino]-N-[(2S)-1-[(4-methylphenyl)methylamino]-1-oxo-3-phenylpropan-2-yl]pentanediamide	1905138: Inhibition of 20S proteasome subunit beta-5i (unknown origin) using Ac-ANW-AMC as substrate and measured after 30 mins	ic50	0.0029	uM
N-[(2R)-1-[[(2S)-3-(4-methoxyphenyl)-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methyl-1H-indene-2-carboxamide	1182706: Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry	ic50	0.0030	uM
N-[(2S)-1-[[(2S)-1-[[(2S)-3-cyclohexyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methyl-1H-indene-2-carboxamide	1182706: Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry	ic50	0.0030	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	4
Arsenic Trioxide	decreases expression, affects cotreatment, increases expression	4
Tretinoin	affects cotreatment, increases expression	4
Acetaminophen	decreases expression, increases expression, affects response to substance	3
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Estradiol	decreases expression, increases expression, affects cotreatment	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
OTX015	decreases expression	1
mivebresib	decreases expression	1
oxyphylla A	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
2,2,2-trichloroethanol	affects cotreatment, increases expression, decreases reaction	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases reaction, increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	increases expression	1
sibutramine	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
monomethylarsonous acid	increases expression	1
K 7174	decreases expression	1

ChEMBL screening assays

262 unique, capped per target: 250 binding, 9 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

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1H2	Abcam A-549 PSMB8 KO 1	Cancer cell line	Male
CVCL_B2PL	Abcam A-549 PSMB8 KO 2	Cancer cell line	Male
CVCL_B7SS	NIHTVBi016-A	Induced pluripotent stem cell	Female
CVCL_B7ST	NIHTVBi017-A	Induced pluripotent stem cell	Male
CVCL_B7SU	NIHTVBi018-A	Induced pluripotent stem cell	Female
CVCL_TH30	HAP1 PSMB8 (-) 1	Cancer cell line	Male
CVCL_TH31	HAP1 PSMB8 (-) 2	Cancer cell line	Male
CVCL_TH32	HAP1 PSMB8 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT04517253	PHASE2/PHASE3	TERMINATED	A Study of Baricitinib (LY3009104) in Adult and Pediatric Japanese Participants With NNS/CANDLE, SAVI, and AGS
NCT01724580	Not specified	APPROVED_FOR_MARKETING	Compassionate Use Protocol for the Treatment of Autoinflammatory Syndromes
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION