PSMA8

Summary

PSMA8 (proteasome 20S subunit alpha 8, HGNC:22985) is a protein-coding gene on chromosome 18q11.2, encoding Proteasome subunit alpha-type 8 (Q8TAA3). Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis.

Predicted to be involved in meiotic cell cycle and proteasome-mediated ubiquitin-dependent protein catabolic process. Located in extracellular exosome and nucleus.

Source: NCBI Gene 143471 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 40 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001025096

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22985
Approved symbol	PSMA8
Name	proteasome 20S subunit alpha 8
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC26605, PSMA7L
Ensembl gene	ENSG00000154611
Ensembl biotype	protein_coding
OMIM	617841
Entrez	143471

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000308268, ENST00000343848, ENST00000415576, ENST00000538664, ENST00000612461

RefSeq mRNA: 4 — MANE Select: NM_001025096 NM_001025096, NM_001025097, NM_001308188, NM_144662

CCDS: CCDS32808, CCDS45842, CCDS45843, CCDS77169

Canonical transcript exons

ENST00000415576 — 7 exons

Exon	Start	End
ENSE00003463506	26144559	26144685
ENSE00003478661	26158122	26158244
ENSE00003502593	26192319	26193355
ENSE00003553955	26179068	26179130
ENSE00003646732	26178830	26178949
ENSE00003658826	26151858	26151982
ENSE00003906978	26133869	26134067

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 82.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2820 / max 65.6462, expressed in 81 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169764	0.2602	80
169765	0.0218	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	82.47	gold quality
sperm	CL:0000019	82.23	gold quality
left testis	UBERON:0004533	81.87	gold quality
testis	UBERON:0000473	81.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.98	gold quality
buccal mucosa cell	CL:0002336	70.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.20	gold quality
adult organism	UBERON:0007023	67.31	gold quality
secondary oocyte	CL:0000655	62.53	gold quality
lymph node	UBERON:0000029	59.42	gold quality
pancreatic ductal cell	CL:0002079	57.77	silver quality
granulocyte	CL:0000094	57.58	gold quality
vermiform appendix	UBERON:0001154	54.97	gold quality
epithelium of nasopharynx	UBERON:0001951	54.45	silver quality
epithelial cell of pancreas	CL:0000083	54.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
nasal cavity epithelium	UBERON:0005384	53.98	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
deltoid	UBERON:0001476	52.35	gold quality
caecum	UBERON:0001153	51.68	gold quality
ileal mucosa	UBERON:0000331	51.38	silver quality
myocardium	UBERON:0002349	50.97	gold quality
quadriceps femoris	UBERON:0001377	49.49	gold quality
middle temporal gyrus	UBERON:0002771	48.74	gold quality
oocyte	CL:0000023	48.60	gold quality
vastus lateralis	UBERON:0001379	48.35	gold quality
tonsil	UBERON:0002372	47.23	gold quality
oviduct epithelium	UBERON:0004804	45.66	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting PSMA8, 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-3646	100.00	73.56	5283
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925

Literature-anchored findings (GeneRIF, showing 1)

• This article provides an overview of some of the components in the human 20 S proteasome. (PMID:12376572)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psma8	ENSDARG00000010965
mus_musculus	Psma8	ENSMUSG00000036743
rattus_norvegicus	Psma8	ENSRNOG00000030363
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), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit alpha-type 8 — Q8TAA3 (reviewed: Q8TAA3)

Alternative names: Proteasome alpha 4 subunit, Proteasome subunit alpha-type 7-like

All UniProt accessions (3): Q8TAA3, A0A087WYS6, F5GY34

UniProt curated annotations — full annotation on UniProt →

Function. Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. The proteasome is a protein complex that degrades unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Required for 20S core proteasome assembly, essential for the degradation of meiotic proteins RAD51 and RPA1 at late prophase I and the progression of meiosis I during spermatogenesis. Localizes to the synaptonemal complex, a ‘zipper’-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I.

Subunit / interactions. Component of the outer alpha-ring of the 20S proteasome core which is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The catalytic chamber with the active sites is on the inside of the barrel. Interacts with canonical subunits of the spermatoproteasome, including proteasome activators PSME4 (also called PA200) and PSME3 (also called PA28-gamma). Interacts with proteasome-interacting proteins chaperones, ubiquitin ligases and ubiquitin specific proteases. Interacts with meiotic proteins cyclin dependent kinase CDK1 and the ATPase TRIP13 as well as proteins of the synaptonemal complex SIX6OS1 and SYCE3.

Subcellular location. Nucleus.

Similarity. Belongs to the peptidase T1A family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TAA3-1	1	yes
Q8TAA3-2	2
Q8TAA3-5	3

RefSeq proteins (4): NP_001020267, NP_001020268, NP_001295117, NP_653263 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000426	Proteasome_asu_N	Domain
IPR001353	Proteasome_sua/b	Family
IPR023332	Proteasome_alpha-type	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR050115	Proteasome_alpha	Family

Pfam: PF00227, PF10584

UniProt features (4 total): splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAA3-F1	84.04	0.33

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 125 (showing top): WHITEHURST_PACLITAXEL_SENSITIVITY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, KEGG_PROTEASOME, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, INAMURA_LUNG_CANCER_SCC_UP, GOBP_ORGANELLE_FISSION, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, AFP1_Q6, AACTTT_UNKNOWN

GO Biological Process (8): spermatogenesis (GO:0007283), proteasomal protein catabolic process (GO:0010498), cell differentiation (GO:0030154), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), meiotic cell cycle (GO:0051321), regulation of meiosis I (GO:0060631), ubiquitin-dependent protein catabolic process (GO:0006511), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (0):

GO Cellular Component (7): nucleus (GO:0005634), cytosol (GO:0005829), proteasome core complex, alpha-subunit complex (GO:0019773), extracellular exosome (GO:0070062), spermatoproteasome complex (GO:1990111), proteasome complex (GO:0000502), proteasome core complex (GO:0005839)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein-containing complex	3
proteasome complex	2
developmental process involved in reproduction	1
male gamete generation	1
protein catabolic process	1
cellular developmental process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
meiosis I	1
regulation of meiotic nuclear division	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
proteasome core complex	1
extracellular vesicle	1
endopeptidase complex	1
catalytic complex	1

Protein interactions and networks

STRING

1708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMA8	PSMB10	P40306	801
PSMA8	PSMB9	P28065	747
PSMA8	PSMB8	P28062	728
PSMA8	PSME4	Q14997	688
PSMA8	PSMB11	A5LHX3	654
PSMA8	PSMB2	P31145	604
PSMA8	PSMA1	P25786	541
PSMA8	SYCP3	Q8IZU3	539
PSMA8	PSME3	P61289	516
PSMA8	PSMC3	P17980	489
PSMA8	PSMC2	P35998	474
PSMA8	MEIKIN	A0A087WXM9	473
PSMA8	PSMD14	O00487	470
PSMA8	PSMC4	P43686	468
PSMA8	PSMD12	O00232	455
PSMA8	NFKB2	Q00653	455

IntAct

33 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
PSMA2	PSMA7	psi-mi:“MI:0914”(association)	0.850
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMB7	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMB2	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMB3	PSMA7	psi-mi:“MI:0914”(association)	0.770
PSMB4	PSMA7	psi-mi:“MI:0914”(association)	0.730
POLR3GL	POLR3A	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB1	PSMA7	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PSMB9	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMA7	PSMG1	psi-mi:“MI:0914”(association)	0.530
PSMA2	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMG2	PSMA7	psi-mi:“MI:0914”(association)	0.530
PSMB7	PSMD12	psi-mi:“MI:0914”(association)	0.530
PSMA8	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
SHC2	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (125): PSMA8 (Affinity Capture-MS), PSMA8 (Affinity Capture-MS), PSMA8 (Affinity Capture-MS), PSMA1 (Co-fractionation), PSMA2 (Co-fractionation), PSMA3 (Co-fractionation), PSMA4 (Co-fractionation), PSMA5 (Co-fractionation), PSMA8 (Co-fractionation), PSMA8 (Co-fractionation), PSMA8 (Co-fractionation), PSMB2 (Co-fractionation), PSMB3 (Co-fractionation), PSMB4 (Co-fractionation), PSMB5 (Co-fractionation)

ESM2 similar proteins: A2YXU2, A2Z3I9, O13268, O14818, O16811, O17586, O23715, O24030, O24362, O24616, O48551, O70435, O81146, O94517, P18422, P21243, P22769, P25788, P30186, P34120, P40303, P48004, P52428, P60900, P60901, P90513, Q0J006, Q10329, Q24178, Q27563, Q2YDE4, Q3ZBG0, Q4R7D9, Q58DU5, Q5RDH8, Q6YT00, Q8TAA3, Q95005, Q9CWH6, Q9LSU0

Diamond homologs: A2Y9X7, A2YVR7, A2YXU2, A2Z3I9, A3CW55, A4FZT6, A4YCU9, A5UJS2, A6VIP0, A7I9C7, B0R2T2, B6YSH9, B8GEZ3, C3MQ43, C3MVG1, C3N5R0, C3NEC6, C3NHC6, C4KHD9, C5A2C2, C6A459, O13268, O14818, O23708, O24030, O24616, O24733, O26782, O29760, O48551, O59219, O73672, O81148, O81149, O94579, P0DKK3, P0DKK4, P17220, P23638, P23639

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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	10	285.5×	1e-22
Regulation of activated PAK-2p34 by proteasome mediated degradation	11	153.2×	2e-21
Cross-presentation of soluble exogenous antigens (endosomes)	12	152.3×	3e-23
Regulation of ornithine decarboxylase (ODC)	11	149.6×	2e-21
Vpu mediated degradation of CD4	11	146.1×	2e-21
Autodegradation of the E3 ubiquitin ligase COP1	11	146.1×	2e-21
Ubiquitin-dependent degradation of Cyclin D	11	146.1×	2e-21
Proteasome assembly	14	142.8×	5e-27

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	12	27.2×	1e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1415 predictions. Top by Δscore:

Variant	Effect	Δscore
18:26134073:G:GT	donor_gain	1.0000
18:26158120:A:AG	acceptor_gain	1.0000
18:26158121:G:GG	acceptor_gain	1.0000
18:26158121:GAA:G	acceptor_gain	1.0000
18:26158121:GAAAT:G	acceptor_gain	1.0000
18:26158240:GGAAG:G	donor_gain	1.0000
18:26158241:GAAG:G	donor_gain	1.0000
18:26158241:GAAGG:G	donor_gain	1.0000
18:26158246:T:A	donor_loss	1.0000
18:26178827:A:AG	acceptor_gain	1.0000
18:26178827:AAG:A	acceptor_gain	1.0000
18:26178828:A:AG	acceptor_gain	1.0000
18:26178828:AG:A	acceptor_gain	1.0000
18:26178828:AGG:A	acceptor_loss	1.0000
18:26178829:G:GG	acceptor_gain	1.0000
18:26178829:GG:G	acceptor_gain	1.0000
18:26178829:GGC:G	acceptor_gain	1.0000
18:26178829:GGCA:G	acceptor_gain	1.0000
18:26178829:GGCAA:G	acceptor_gain	1.0000
18:26178945:TAGAA:T	donor_gain	1.0000
18:26178946:AGAA:A	donor_gain	1.0000
18:26178946:AGAAG:A	donor_loss	1.0000
18:26178947:GAA:G	donor_gain	1.0000
18:26178947:GAAG:G	donor_gain	1.0000
18:26178949:AG:A	donor_loss	1.0000
18:26178950:G:GG	donor_gain	1.0000
18:26178951:TAA:T	donor_loss	1.0000
18:26179063:ATTAG:A	acceptor_gain	1.0000
18:26179064:T:G	acceptor_gain	1.0000
18:26179066:A:AG	acceptor_gain	1.0000

AlphaMissense

1628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:26133999:T:C	F12L	1.000
18:26134001:C:A	F12L	1.000
18:26134001:C:G	F12L	1.000
18:26134012:G:A	G16E	0.999
18:26158147:G:C	R133T	0.999
18:26134000:T:G	F12C	0.998
18:26134012:G:T	G16V	0.998
18:26151907:C:G	C99W	0.998
18:26151921:T:C	L104P	0.998
18:26151968:G:C	A120P	0.998
18:26158148:A:C	R133S	0.998
18:26158148:A:T	R133S	0.998
18:26158150:C:A	P134H	0.998
18:26158225:G:A	G159D	0.998
18:26158225:G:T	G159V	0.998
18:26158239:T:A	W164R	0.998
18:26158239:T:C	W164R	0.998
18:26178843:G:A	G170D	0.998
18:26133999:T:G	F12V	0.997
18:26134000:T:C	F12S	0.997
18:26134011:G:A	G16R	0.997
18:26134011:G:C	G16R	0.997
18:26134018:T:A	L18H	0.997
18:26134025:A:C	Q20H	0.997
18:26134025:A:T	Q20H	0.997
18:26134036:C:A	A24D	0.997
18:26144560:T:A	V35D	0.997
18:26151897:G:C	R96P	0.997
18:26151969:C:A	A120E	0.997
18:26158152:T:C	F135L	0.997

dbSNP variants (sampled 300 via entrez): RS1000028220 (18:26157445 C>T), RS1000190128 (18:26185992 A>C), RS1000275566 (18:26164734 G>T), RS1000305229 (18:26137937 G>A), RS1000389151 (18:26150981 A>G), RS1000459935 (18:26164544 G>C), RS1000499058 (18:26157548 T>C), RS1000550617 (18:26162599 C>T), RS1000570759 (18:26137583 T>C), RS1000603017 (18:26162895 A>G), RS1000724765 (18:26179231 T>C), RS1000791256 (18:26138341 G>C), RS1000827971 (18:26192568 T>A,G), RS1000843394 (18:26138747 TG>T), RS1000863004 (18:26192847 A>G)

Disease associations

OMIM: gene MIM:617841 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001966_3	Rhegmatogenous retinal detachment	2.000000e-06
GCST002127_20	Periodontitis (Mean PAL)	5.000000e-06
GCST002127_35	Periodontitis (Mean PAL)	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 41,720 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL451887	CARFILZOMIB	4	12,508
CHEMBL2141296	IXAZOMIB	3	6,022
CHEMBL371405	MARIZOMIB	3	7,332
CHEMBL2103884	OPROZOMIB	2	2,738

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

ChEMBL bioactivities

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

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

PubChem BioAssay actives

280 with measured affinity, of 810 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
methyl (2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoate	277357: Inhibition of human 20S proteasome	ic50	0.0006	uM
[(1R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-(pyrazine-2-carbonyl)amino]-3-methylbutyl]boronic acid	2131634: Binding affinity to 20s proteosome (unknown origin) assessed as inhibition constant	ki	0.0006	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0009	uM
(1R,4R,5S)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	277357: Inhibition of human 20S proteasome	ic50	0.0010	uM
(1R,4R,5S)-4-(2-chloroethyl)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	1853759: Inhibition of 20S proteasome (unknown origin) by fluorescence based assay	ic50	0.0013	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0015	uM
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-2-cyclopentyl-10-(1,3-dioxoisoindol-2-yl)decanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0020	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0022	uM
4-N-(4-benzoylphenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0024	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0024	uM
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0025	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0027	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0027	uM
4-N-(4-fluorophenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0034	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methyl-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0034	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0036	uM
4-N-(1,3-benzothiazol-2-yl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0039	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0039	uM
[(1R)-1-[[2-[(2,5-dibromobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0040	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0040	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(2S)-3-(4-hydroxyphenyl)-1-[[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0043	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3,4-thiadiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-chlorophenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-methoxyphenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0048	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0050	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0051	uM
(2S)-N’-(2,2-dimethylpropyl)-2-[[4-[methyl(pyridine-3-carbonyl)amino]piperidine-1-carbonyl]amino]-N-[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]butanediamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0052	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0056	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
benzyl N-[(2S)-1-[[(2R)-1-[(1R,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]-4-phenylbutan-2-yl]amino]-1-oxopropan-2-yl]carbamate	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
(2S)-2-[(2,5-dichlorobenzoyl)amino]-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0059	uM
(2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoic acid	277357: Inhibition of human 20S proteasome	ic50	0.0060	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0060	uM
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-10-cyano-2-cyclopentyldecanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0060	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0063	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,2-oxazol-3-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0064	uM
(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pentanamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0064	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0065	uM
Ixazomib	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0065	uM
4-N-(4-chlorophenyl)-1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methylpiperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0069	uM
(2S)-N-[(2S,3R,4R)-3-hydroxy-5-[[(2S)-1-[(2-hydroxy-4-methoxyphenyl)methylamino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxo-1-phenyl-4-[(3,4,5-trimethoxyphenyl)methylamino]pentan-2-yl]-3,3-dimethyl-2-[(2-naphthalen-1-ylacetyl)amino]butanamide	3027: Tested in vitro for inhibition of chymotrypsin like activity of purified human 20S proteasome	ic50	0.0070	uM
Carfilzomib	1770085: Inhibition of human 20S proteasome chymotrypsin-like activity in human RPMI-8226 cells using Suc-LLVY-AMC as fluorogenic substrate incubated for 3 hrs by fluorescence assay	ic50	0.0070	uM
(2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-naphthalen-1-ylacetyl)amino]propanoyl]amino]-N-[1-(4-hydroxyphenyl)-3-oxopropan-2-yl]-3-methylbutanamide	248827: Inhibitory concentration to inhibit chymotrypsin-like activity of 20S proteasome prepared from human leukemia HL-60 cells was determined	ic50	0.0070	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-(pyrazine-2-carbonylamino)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0071	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
quercitrin	decreases expression	1
benzo(e)pyrene	increases methylation	1
bisphenol S	decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	increases methylation	1
Phthalic Acids	decreases methylation	1
Rotenone	decreases expression	1

ChEMBL screening assays

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

Representative assays (with source publication via chembl_document):

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

Clinical trials (associated diseases)

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