PSMB6

Summary

PSMB6 (proteasome 20S subunit beta 6, HGNC:9543) is a protein-coding gene on chromosome 17p13.2, encoding Proteasome subunit beta type-6 (P28072). 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 96.6% 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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5694 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total — 1 pathogenic
• GTEx eGene: eQTL in 7 tissues, sQTL in 30 (q < 0.05)
• ChEMBL bioactivity: 5 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 96.6% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.17 (intermediate), LOEUF 0.72 (unconstrained)
• MANE Select transcript: NM_002798
• Interaction hub: 2,736 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9543
Approved symbol	PSMB6
Name	proteasome 20S subunit beta 6
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Y, DELTA
Ensembl gene	ENSG00000142507
Ensembl biotype	protein_coding
OMIM	600307
Entrez	5694

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 12 nonsense_mediated_decay, 9 protein_coding, 2 retained_intron

MANE Select: ENST00000270586

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 1

ENST00000270586, ENST00000571309, ENST00000575079, ENST00000575643, ENST00000614486, ENST00000904435, ENST00000939638, ENST00000939639, ENST00000939640, ENST00001010333, ENST00001010334, ENST00001089455, ENST00001089459, ENST00001089460, ENST00001089461, ENST00001089468, ENST00001089471, ENST00001089473, ENST00001089475, ENST00001092503, ENST00001092504, ENST00001092505, ENST00001137481

RefSeq mRNA: 2 — MANE Select: NM_002798 NM_001270481, NM_002798

CCDS: CCDS11056, CCDS73944

Canonical transcript exons

ENST00000270586 — 6 exons

Exon	Start	End
ENSE00000954599	4798280	4798495
ENSE00001126119	4797682	4797811
ENSE00001126122	4797438	4797569
ENSE00001126128	4796728	4796795
ENSE00003662921	4798009	4798153
ENSE00003847846	4796164	4796296

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 102.7651 / max 431.3188, expressed in 1828 samples.

Highest expression (Bgee): gastrocnemius, hindlimb stylopod muscle, body of tongue, muscle of leg, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PSMB6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 30 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	2.6e-35	-1.46	17:4797326:A:G
Cells Cultured fibroblasts	sqtl	1.8e-18	-1.22	17:4797326:A:G
Artery Tibial	sqtl	6.5e-18	-1.18	17:4797326:A:G
Skin Sun Exposed Lower leg	sqtl	9.9e-17	-1.13	17:4797724:C:T
Esophagus Mucosa	sqtl	7.5e-16	-1.24	17:4797724:C:T
Nerve Tibial	sqtl	9.0e-13	+1.01	17:4808935:C:T
Skin Not Sun Exposed Suprapubic	sqtl	2.7e-11	+0.98	17:4797326:A:G
Adipose Subcutaneous	sqtl	2.2e-10	+0.95	17:4797326:A:G
Esophagus Muscularis	sqtl	2.3e-10	+1.20	17:4797724:C:T
Esophagus Gastroesophageal Junction	sqtl	3.3e-09	-1.12	17:4797326:A:G
Adipose Visceral Omentum	sqtl	5.7e-09	+0.88	17:4793960:G:A
Cells EBV-transformed lymphocytes	sqtl	1.4e-08	-1.23	17:4797326:A:G
Heart Left Ventricle	sqtl	8.2e-08	+1.21	17:4797326:A:G
Colon Transverse	sqtl	1.0e-07	+1.07	17:4797326:A:G
Artery Aorta	sqtl	2.1e-07	+1.00	17:4797326:A:G
Thyroid	sqtl	2.8e-07	+0.83	17:4797326:A:G
Breast Mammary Tissue	sqtl	8.2e-07	+0.96	17:4797724:C:T
Colon Sigmoid	sqtl	1.2e-06	+1.04	17:4797326:A:G
Heart Atrial Appendage	sqtl	1.6e-06	+1.01	17:4797326:A:G
Lung	sqtl	3.8e-06	+0.87	17:4797326:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
158944	102.7651	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.64	gold quality
body of tongue	UBERON:0011876	98.54	gold quality
muscle of leg	UBERON:0001383	98.46	gold quality
apex of heart	UBERON:0002098	98.43	gold quality
heart left ventricle	UBERON:0002084	98.37	gold quality
islet of Langerhans	UBERON:0000006	98.36	gold quality
cardiac ventricle	UBERON:0002082	98.33	gold quality
muscle organ	UBERON:0001630	98.27	gold quality
smooth muscle tissue	UBERON:0001135	98.25	gold quality
pharyngeal mucosa	UBERON:0000355	98.24	gold quality
right atrium auricular region	UBERON:0006631	98.18	gold quality
heart	UBERON:0000948	98.08	gold quality
ventricular zone	UBERON:0003053	98.05	gold quality
lower esophagus	UBERON:0013473	98.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.05	gold quality
cardiac atrium	UBERON:0002081	98.02	gold quality
tongue	UBERON:0001723	97.99	gold quality
rectum	UBERON:0001052	97.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.94	gold quality
popliteal artery	UBERON:0002250	97.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.91	gold quality
tibial artery	UBERON:0007610	97.91	gold quality
triceps brachii	UBERON:0001509	97.90	gold quality
left coronary artery	UBERON:0001626	97.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.90	gold quality
prefrontal cortex	UBERON:0000451	97.89	gold quality
esophagus	UBERON:0001043	97.89	gold quality
right adrenal gland	UBERON:0001233	97.86	gold quality
coronary artery	UBERON:0001621	97.86	gold quality
ganglionic eminence	UBERON:0004023	97.86	gold quality
vastus lateralis	UBERON:0001379	97.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.84	gold quality
aorta	UBERON:0000947	97.83	gold quality
quadriceps femoris	UBERON:0001377	97.82	gold quality
esophagus mucosa	UBERON:0002469	97.81	gold quality
right coronary artery	UBERON:0001625	97.77	gold quality
type B pancreatic cell	CL:0000169	97.76	gold quality
thoracic aorta	UBERON:0001515	97.75	gold quality
mucosa of transverse colon	UBERON:0004991	97.75	gold quality
ascending aorta	UBERON:0001496	97.73	gold quality
skin of leg	UBERON:0001511	97.72	gold quality
left ventricle myocardium	UBERON:0006566	97.72	gold quality
right adrenal gland cortex	UBERON:0035827	97.72	gold quality
skeletal muscle tissue	UBERON:0001134	97.71	gold quality
diaphragm	UBERON:0001103	97.68	gold quality
stromal cell of endometrium	CL:0002255	97.67	gold quality
left adrenal gland	UBERON:0001234	97.64	gold quality
descending thoracic aorta	UBERON:0002345	97.63	gold quality
ectocervix	UBERON:0012249	97.62	gold quality
body of stomach	UBERON:0001161	97.61	gold quality
embryo	UBERON:0000922	97.60	gold quality
skin of abdomen	UBERON:0001416	97.59	gold quality
superior surface of tongue	UBERON:0007371	97.58	gold quality
nipple	UBERON:0002030	97.56	gold quality
left adrenal gland cortex	UBERON:0035825	97.55	gold quality
adrenal cortex	UBERON:0001235	97.52	gold quality
saphenous vein	UBERON:0007318	97.50	gold quality
muscle tissue	UBERON:0002385	97.49	gold quality
oocyte	CL:0000023	97.43	gold quality
pons	UBERON:0000988	97.43	gold quality
nucleus accumbens	UBERON:0001882	97.43	gold quality
vena cava	UBERON:0004087	97.43	gold quality
mucosa of stomach	UBERON:0001199	97.39	gold quality
deltoid	UBERON:0001476	97.39	gold quality
renal medulla	UBERON:0000362	97.36	gold quality
putamen	UBERON:0001874	97.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.36	gold quality
gingiva	UBERON:0001828	97.35	gold quality
left uterine tube	UBERON:0001303	97.33	gold quality
amygdala	UBERON:0001876	97.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.32	gold quality
metanephros cortex	UBERON:0010533	97.32	gold quality
zone of skin	UBERON:0000014	97.31	gold quality
fundus of stomach	UBERON:0001160	97.31	gold quality
adenohypophysis	UBERON:0002196	97.30	gold quality
cortical plate	UBERON:0005343	97.27	gold quality
penis	UBERON:0000989	97.26	gold quality
biceps brachii	UBERON:0001507	97.26	gold quality
lower esophagus mucosa	UBERON:0035834	97.24	gold quality
gingival epithelium	UBERON:0001949	97.23	gold quality
caudate nucleus	UBERON:0001873	97.22	gold quality
pituitary gland	UBERON:0000007	97.19	gold quality
right frontal lobe	UBERON:0002810	97.19	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.18	gold quality
sigmoid colon	UBERON:0001159	97.14	gold quality
spinal cord	UBERON:0002240	97.14	gold quality
body of uterus	UBERON:0009853	97.13	gold quality
adrenal gland	UBERON:0002369	97.12	gold quality
dorsal root ganglion	UBERON:0000044	97.11	gold quality
lymph node	UBERON:0000029	97.10	gold quality
monocyte	CL:0000576	97.08	gold quality
heart right ventricle	UBERON:0002080	97.08	gold quality
transverse colon	UBERON:0001157	97.05	gold quality
gluteal muscle	UBERON:0002000	97.05	gold quality
granulocyte	CL:0000094	97.04	gold quality
mononuclear cell	CL:0000842	97.04	gold quality
vermiform appendix	UBERON:0001154	97.04	gold quality
upper lobe of left lung	UBERON:0008952	97.04	gold quality
leukocyte	CL:0000738	97.01	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	20.96
E-MTAB-7303	no	1407.87
E-GEOD-106540	no	1134.83
E-MTAB-6379	no	717.15
E-CURD-89	no	471.76
E-MTAB-7052	no	425.73
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	316.9	medium
Tongue	tissue	316.7
Caudate putamen	tissue	309.4
Frontal cortex	tissue	265.3
Heart muscle	tissue	174.0	medium
Liver	tissue	172.4	high
Parathyroid gland	tissue	162.8	medium
Epididymis	tissue	142.5	medium
Thymus	tissue	137.3
Tonsil	tissue	131.5	medium
Smooth muscle	tissue	126.3	medium
Kidney	tissue	125.5	medium
Esophagus	tissue	124.8	medium
Bone marrow	tissue	119.7	medium
Spinal cord	tissue	116.9
Pons	tissue	116.6
Placenta	tissue	112.5	high
Rectum	tissue	111.0	medium
Seminal vesicle	tissue	107.5	high
Medulla oblongata	tissue	104.7
Substantia nigra	tissue	104.2
Thalamus	tissue	103.9
Urinary bladder	tissue	103.3	high
Midbrain	tissue	102.3
Superior colliculi	tissue	102.1
Breast	tissue	100.2	medium
Skin 1	tissue	98.4	high
Colon	tissue	97.5	medium
Salivary gland	tissue	94.1	medium
Pancreas	tissue	93.6	medium
Fallopian tube	tissue	93.3	medium
Hypothalamus	tissue	91.8
Putamen	tissue	90.3
Ovary	tissue	89.4	medium
Vagina	tissue	88.8	medium
Hippocampal formation	tissue	87.3
Cervix	tissue	87.0	medium
Adipose tissue	tissue	86.5	medium
Corpus callosum	tissue	85.9
Lymph node	tissue	84.2	low
Septum	tissue	84.2
Periaqueductal gray	tissue	83.5
Pituitary gland	tissue	83.1
Thyroid gland	tissue	83.0	high
Lung	tissue	81.2	medium
Adrenal gland	tissue	80.5	high
Cerebral cortex	tissue	79.7	high
Somatosensory cortex	tissue	79.7
Prostate	tissue	79.5	medium
Ventral forebrain	tissue	79.1
Stomach 1	tissue	77.7	medium
Basal ganglia	tissue	77.7	high
Appendix	tissue	77.5	medium
Occipital cortex	tissue	75.8
Motor cortex	tissue	73.9
Temporal cortex	tissue	72.6
Duodenum	tissue	72.3	high
Prefrontal cortex	tissue	72.2
Endometrium 1	tissue	72.2	medium
Locus coeruleus	tissue	72.0

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (135.5), Ventral spinal cord (116.9), Dorsal spinal cord (98.2), Dorsal hippocampus (87.3), White matter (85.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

Functional genomics

gnomAD constraint: pLI 0.17, LOEUF 0.721, missense Z 1.14 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000270586 — one region, missense o/e 0.84. DepMap (CRISPR cell-line fitness): dependent in 96.6% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): AsPC-1 (-3.489), DAN-G (-3.451), OV-90 (-3.237), C2BBe1 (-3.221), TF-1 (-3.181), SK-BR-3 (-3.162), EOL-1 (-3.13), SCC-4 (-3.128), BHT-101 (-3.114), COLO-678 (-3.073), ONCO-DG-1 (-3.061), A-375 (-3.038), VCaP (-2.962), Panc 02.03 (-2.945), Hs 294T (-2.926).

Literature-anchored findings (GeneRIF, showing 2)

• results indicate ZAG as a possible predictive marker of Gleason grade. The inverse association between grade and tissue expression with a rising serum protein level is similar to that seen with prostate-specific antigen. In addition, the results for both ZAG and PSMB-6 highlight the challenges in trying to associate the protein levels in serum with tissue expression (PMID:20661134)
• 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)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb6	ENSDARG00000002240
mus_musculus	Psmb6	ENSMUSG00000018286
rattus_norvegicus	Psmb6l1	ENSRNOG00000011827
rattus_norvegicus	Psmb6	ENSRNOG00000019551
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), 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
Pongo abelii	Q5R8S2	100.0%	Diamond
Mus musculus bactrianus	O35522	99.5%	Diamond
Mus spicilegus	O35524	99.5%	Diamond
Salmo salar	A7KE01	99.1%	Diamond
Mus terricolor	O35521	99.1%	Diamond
Mus platythrix	O35523	98.2%	Diamond
Oncorhynchus mykiss	Q9PT26	98.2%	Diamond
Sus scrofa	A1XQU1	97.8%	Diamond
Bos taurus	Q2TBP0	97.8%	Diamond
Arabidopsis thaliana	O23710	97.4%	Diamond
Canis lupus familiaris	Q5W416	86.5%	Diamond
Nicotiana tabacum	P93395	85.1%	Diamond
Oryzias latipes	Q8UW64	83.9%	Diamond
Gallus gallus	P34065	70.4%	Diamond
Dictyostelium discoideum	Q54QR2	64.2%	Diamond
Schizosaccharomyces pombe 972h-	O43063	62.5%	Diamond
Saccharomyces cerevisiae S288C	P38624	62.5%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SR11	55.4%	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
GLTPD2	protein-coding	388323
MINK1	protein-coding	50488
PLD2	protein-coding	5338
C17orf114	protein-coding	119139905
VMO1	protein-coding	284013
TM4SF5	protein-coding	9032
CXCL16	protein-coding	58191
ZMYND15	protein-coding	84225

Protein

Protein identifiers

Proteasome subunit beta type-6 — P28072 (reviewed: P28072)

Alternative names: Macropain delta chain, Multicatalytic endopeptidase complex delta chain, Proteasome delta chain, Proteasome subunit Y, Proteasome subunit beta-1

All UniProt accessions (4): A0A087X2I4, P28072, I3L3X7, Q6IAT9

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, PSMB6 displays a peptidylglutamyl-hydrolizing activity also termed postacidic or caspase-like activity, meaning that the peptides bond hydrolysis occurs directly after acidic residues.

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 protein Tat.

Subcellular location. Cytoplasm. Nucleus.

Induction. Down-regulated by IFNG/IFN-gamma (at protein level). Up-regulated in anaplastic thyroid cancer cell lines.

Similarity. Belongs to the peptidase T1B family.

RefSeq proteins (2): NP_001257410, NP_002789* (*=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, helix 11, turn 2, modified residue 2, initiator methionine 1, propeptide 1, chain 1, active site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 146 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
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
8CVR	Human 20S proteasome with MG-132	ELECTRON MICROSCOPY	2.7
6KWY	human PA200-20S complex	ELECTRON MICROSCOPY	2.72
9MBP	Substrate-engaged human 26S proteasome bound to midnolin with RPT1 at top of spiral …	ELECTRON MICROSCOPY	2.75
7NAN	Human 20S proteasome core particle	ELECTRON MICROSCOPY	2.8
8TM6	Human premature 20S proteasome assembly intermediate	ELECTRON MICROSCOPY	2.8
9NKG	Structure of substrate engaged MIDN-bound human 26S proteasome, EB-MIDN (Composite map)	ELECTRON MICROSCOPY	2.8
8QYO	Human proteasome 20S core particle	ELECTRON MICROSCOPY	2.84
8QYN	Human 20S proteasome assembly intermediate structure 5	ELECTRON MICROSCOPY	2.88
4R67	Human constitutive 20S proteasome in complex with carfilzomib	X-RAY DIFFRACTION	2.89
7NAO	Human PA28-20S proteasome complex	ELECTRON MICROSCOPY	2.9
8CXB	Human PA28-20S (PA28-4a3b)	ELECTRON MICROSCOPY	2.9
9BV3	M1B Midnolin-Proteasome	ELECTRON MICROSCOPY	2.9
9K4J	Structure of substrate-engaged human 26S proteasome RP-CP subcomplex in state EA1.0	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28072-F1	89.14	0.80

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): cytosol; nucleoplasm; mitochondria

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
35	nucleophile

Post-translational modifications (2)

Type	Positions
N-acetylalanine	2
Phosphothreonine	69

Function

Pathways and Gene Ontology

Reactome pathways

58 curated (TAS) of 172; 13 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 172 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-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 ⚕	—
R-HSA-1643685	Disease ⚕	—

MSigDB gene sets: 376 (showing top): MORF_MTA1, 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, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION

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 (6): endopeptidase activity (GO:0004175), threonine-type endopeptidase activity (GO:0004298), cadherin binding (GO:0045296), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (10): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome core complex (GO:0005839), synaptic vesicle (GO:0008021), proteasome core complex, beta-subunit complex (GO:0019774), proteasome storage granule (GO:0034515), extracellular exosome (GO:0070062)

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

49 GO namespaces:

Category	Terms
proteasomal protein catabolic process	3
cellular anatomical structure	3
intracellular protein-containing complex	2
intracellular anatomical structure	2
cytoplasm	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
cell adhesion molecule binding	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
proteasome core complex	1
protein-containing complex	1
intracellular membraneless organelle	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 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
extracellular exosome	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
proteasome complex	CC	direct assay
proteasome core complex	CC	direct assay
cadherin binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 2,736 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB6	PSMB2	P31145	821
PSMB6	PSMB7	Q99436	801
PSMB6	PSMB5	P28074	786
PSMB6	CTRL	P40313	781
PSMB6	PSMA4	P25789	709
PSMB6	PSMA5	P28066	708
PSMB6	PSMB4	P28070	706
PSMB6	PSMA1	P25786	699
PSMB6	PSMA3	P25788	682
PSMB6	PSMA6	P34062	682
PSMB6	PSMB3	P31147	681
PSMB6	PSMA2	P25787	646
PSMB6	PSME3	P61289	634
PSMB6	PSMC1	P49014	621
PSMB6	PSMB1	P20618	610

IntAct

Human interaction partners of PSMB6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
PSMB7	physical association	0.800	2
POMP	physical association	0.760	2
HTT	physical association	0.560	3
NDOR1	physical association	0.560	3
MDM2	physical association	0.400	1
ARHGEF7	association	0.350	1
PSMD1	association	0.350	1
EZH2	physical association	0.000	1
HLA-B	physical association	0.000	1
IKBKE	physical association	0.000	1
TRAF6	physical association	0.000	1

BioGRID (481 interactions; top human partners by supporting records): PSMA2 (Co-fractionation; 12 records), PSMB7 (Affinity Capture-MS; 12 records), PSMB2 (Co-fractionation; 9 records), PSMB4 (Affinity Capture-MS; 9 records), PSMA4 (Co-fractionation; 8 records), PSMA6 (Co-fractionation; 8 records), PSMB1 (Co-fractionation; 8 records), PSMB3 (Co-fractionation; 8 records), PSMD14 (Co-fractionation; 8 records), PSMA1 (Co-fractionation; 7 records), PSMA5 (Co-fractionation; 7 records), PSMA7 (Co-fractionation; 7 records), PSMB5 (Co-fractionation; 7 records), PSMB8 (Co-fractionation; 7 records), PSMA3 (Co-fractionation; 6 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PSMB6	“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

Disease & clinical

Genetic variants

Variant evidence for PSMB6: 39 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	31
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59563	GRCh38/hg38 17p13.2-13.1(chr17:3601515-7178024)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PSMB6’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 422):

Position(s)	Effect	Δscore	Sites
17:4797556	donor_gain	1.0000
17:4797570–4797571	donor_loss	1.0000	4
17:4798004	acceptor_gain	1.0000
17:4798007–4798008	acceptor_loss	1.0000	5
17:4798154–4798155	donor_loss	1.0000	5
17:4798278	acceptor_loss	1.0000	2
17:4796274	donor_gain	0.9900
17:4796297–4796298	donor_loss	0.9900	5
17:4796352	donor_gain	0.9900
17:4797436–4797437	acceptor_loss	0.9900	6

AlphaMissense

860 missense substitutions predicted likely pathogenic (of 1,526 scored), across 185 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
M153	9	0.858	0.984
D51	8	0.999	1.000
D201	8	0.999	1.000
D85	8	0.994	0.999
D174	8	0.990	0.998
D138	8	0.981	0.993
S204	8	0.973	0.999
D66	8	0.961	0.996
S166	8	0.954	0.999
F189	8	0.940	0.998
F117	8	0.935	0.987
M198	8	0.875	0.972
D91	8	0.866	0.975
K67	7	0.996	1.000
F42	7	0.987	0.999
C77	7	0.971	1.000
C78	7	0.970	1.000
W137	7	0.968	0.989
F76	7	0.953	0.989
M181	7	0.948	0.983

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
Lung Adenocarcinoma (TCGA)	unfavorable	9.82e-05
Breast Invasive Carcinoma (validation)	unfavorable	0.000258

Disease associations

OMIM: gene MIM:600307 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1944496 (SINGLE PROTEIN), CHEMBL2364701 (PROTEIN COMPLEX), 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)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — T1: Proteasome

Binding affinities (BindingDB)

150 measured of 190 human assays (190 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
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
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
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
CHEMBL2114122	IC50	20 nM
TP-109	IC50	20 nM
CHEMBL5173758	IC50	20 nM

ChEMBL bioactivities

318 potent at pChembl≥5 of 342 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

317 with measured affinity, of 1003 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, increases expression	3
Arsenic	affects methylation, decreases expression, increases abundance, increases expression	3
Particulate Matter	increases reaction, decreases expression, increases abundance, affects cotreatment, affects expression	3
perfluorooctane sulfonic acid	increases expression	2
Rotenone	decreases reaction, increases expression, affects reaction, affects binding, increases reaction	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
quercitrin	decreases expression	1
arsenite	increases reaction, affects binding	1
sulforaphane	decreases reaction, increases expression	1
cobaltous chloride	increases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
arsenic trichloride	decreases expression, increases abundance	1
microcystin RR	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
epoxomicin	affects reaction, decreases reaction, increases expression	1
chloropicrin	affects expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
bisphenol B	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
stattic	decreases expression	1

ChEMBL screening assays

173 unique, capped per target: 164 binding, 6 admet, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1948739	Binding	Binding affinity to LMPY/beta1 in human PC3 cells at 10 to 20 uM after 1.5 hrs by Western blotting	A bright approach to the immunoproteasome: development of LMP2/β1i-specific imaging probes. — *Bioorg Med Chem*
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 PSMB6 across ~30M SureChEMBL compounds — explore on Sugi Predict.