SENP8

Summary

SENP8 (SUMO peptidase family member, NEDD8 specific, HGNC:22992) is a protein-coding gene on chromosome 15q23, encoding Sentrin-specific protease 8 (Q96LD8). Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.

This gene encodes a cysteine protease that is a member of the sentrin-specific protease family. The encoded protein is involved in processing and deconjugation of the ubiquitin-like protein termed, neural precursor cell expressed developmentally downregulated 8. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 123228 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 16 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_145204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22992
Approved symbol	SENP8
Name	SUMO peptidase family member, NEDD8 specific
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	NEDP1, DEN1, HsT17512
Ensembl gene	ENSG00000166192
Ensembl biotype	protein_coding
OMIM	608659
Entrez	123228

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000340912, ENST00000542035, ENST00000564082, ENST00000564863, ENST00000567794, ENST00000919436

RefSeq mRNA: 5 — MANE Select: NM_145204 NM_001166340, NM_001172109, NM_001172110, NM_001172111, NM_145204

CCDS: CCDS10240

Canonical transcript exons

ENST00000340912 — 2 exons

Exon	Start	End
ENSE00001386768	72139577	72143692
ENSE00001521305	72118403	72118464

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 96.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8055 / max 112.9415, expressed in 1706 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147559	5.3400	1608
147557	1.0096	625
147558	0.4560	190

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.52	gold quality
secondary oocyte	CL:0000655	87.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.66	gold quality
right testis	UBERON:0004534	80.30	gold quality
left testis	UBERON:0004533	79.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.68	gold quality
oocyte	CL:0000023	78.61	gold quality
testis	UBERON:0000473	78.57	gold quality
islet of Langerhans	UBERON:0000006	75.81	gold quality
muscle of leg	UBERON:0001383	75.31	gold quality
gastrocnemius	UBERON:0001388	75.13	gold quality
cortical plate	UBERON:0005343	73.59	gold quality
ventricular zone	UBERON:0003053	73.05	gold quality
stromal cell of endometrium	CL:0002255	72.47	gold quality
deltoid	UBERON:0001476	71.83	silver quality
ganglionic eminence	UBERON:0004023	71.65	gold quality
biceps brachii	UBERON:0001507	70.85	silver quality
prefrontal cortex	UBERON:0000451	70.19	gold quality
heart left ventricle	UBERON:0002084	69.93	gold quality
tibialis anterior	UBERON:0001385	69.91	silver quality
cardiac ventricle	UBERON:0002082	69.40	gold quality
metanephros cortex	UBERON:0010533	68.79	gold quality
mucosa of transverse colon	UBERON:0004991	68.59	gold quality
bone marrow cell	CL:0002092	68.58	silver quality
adrenal tissue	UBERON:0018303	68.22	gold quality
skeletal muscle tissue	UBERON:0001134	67.98	gold quality
ileal mucosa	UBERON:0000331	67.88	gold quality
apex of heart	UBERON:0002098	67.86	gold quality
smooth muscle tissue	UBERON:0001135	67.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting SENP8, 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-4692	100.00	67.32	2066
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-376B-5P	98.46	66.40	606

Literature-anchored findings (GeneRIF, showing 13)

• NEDP1 is likely to play an important role in ubiquitin-mediated proteolysis by controlling the activity of SCF complexes (PMID:12730221)
• results suggest a unique role for NEDD8-specific protease 1(DEN1) in regulating the modification of cullin 1 by Nedd8 protein (PMID:12759363)
• X-ray structures of the human Nedd8-specific protease, Den1, in a complex with the inhibitor Nedd8 aldehyde, thus revealing a model for the tetrahedral transition state intermediate generated during proteolysis (PMID:15567417)
• Data show that the stability of MDM2 is regulated by NEDD8 pathway and identify NEDP1 that deneddylates MDM2, resulting in MDM2 destabilization concomitant with p53 activation. (PMID:19784069)
• the specificity of NEDD8-specific peptidase SENP8 (PMID:22110750)
• Data indicate that overexpression of SENP8, a NEDD8-specific cysteine protease, resulted in deNEDDylation of E2F1 and promoted its transactivation activity at the p73 gene. (PMID:23001041)
• A role for SENP8 as a central regulator of the inflammatory process is identified using knockdown and overexpression approaches. (PMID:23209320)
• We analyzed whether CSN1 alone can increase DEN1 degradation in HeLa cells.these data suggest that the COP9 signalosome supports proteasome-dependent protein degradation of DEN1/DenA in fungi and in human cells. (PMID:23408908)
• In endothelial dysfunction, HDAC2 levels were reciprocally regulated by ectopic expression of NEDD8 and the de-NEDDylating enzyme SENP8. (PMID:25655932)
• the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. (PMID:26403403)
• Furthermore, the authors characterized SENP8/DEN1 as the protease that counteracts Ubc12 auto-neddylation, and observed aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway components in SENP8-deficient cells. (PMID:28475037)
• Impairment of NEDDylation by Ubc12 knockout enhances PCNA ubiquitination and promotes PCNA-poleta interaction, while up-regulation of NEDDylation by NEDD8 overexpression or NEDP1 deletion reduces the excessive accumulation of ubiquitinated PCNA. Moreover, Ubc12 knockout decreases cell sensitivity to H2O2-induced oxidative stress, but NEDP1 deletion aggravates this sensitivity (PMID:28831681)
• The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity. (PMID:31577950)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	senp8	ENSDARG00000019595
mus_musculus	Senp8	ENSMUSG00000051705
rattus_norvegicus	Senp8	ENSRNOG00000075500
drosophila_melanogaster	CG1503	FBGN0031157
drosophila_melanogaster	Den1	FBGN0033716
caenorhabditis_elegans		WBGENE00006738

Paralogs (2): FAM76A (ENSG00000009780), FAM76B (ENSG00000077458)

Protein

Protein identifiers

Sentrin-specific protease 8 — Q96LD8 (reviewed: Q96LD8)

Alternative names: Deneddylase-1, NEDD8-specific protease 1, Protease, cysteine 2, Sentrin/SUMO-specific protease SENP8

All UniProt accessions (4): H3BS71, H3BTJ8, H3BTK5, Q96LD8

UniProt curated annotations — full annotation on UniProt →

Function. Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.

Tissue specificity. Broadly expressed, with highest levels in kidney and pancreas.

Similarity. Belongs to the peptidase C48 family.

RefSeq proteins (5): NP_001159812, NP_001165580, NP_001165581, NP_001165582, NP_660205* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003653	Peptidase_C48_C	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR044613	Nep1/2-like	Family

Pfam: PF02902

UniProt features (44 total): mutagenesis site 12, helix 12, strand 9, active site 3, turn 3, chain 1, region of interest 1, sequence conflict 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2BKR	X-RAY DIFFRACTION	1.9
2BKQ	X-RAY DIFFRACTION	2
1XT9	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LD8-F1	96.81	0.95

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 (3): 102; 119; 163 (nucleophile)

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (12):

Position	Phenotype
58	no effect on activity.
74	no effect on activity.
77	no effect on activity.
91	abolishes activity.
102	abolishes activity.
103	strongly reduces activity.
119	abolishes activity.
157	no effect on activity.
163	abolishes activity.
10	no effect on activity.
26	strongly reduces activity.
29	abolishes activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5689603	UCH proteinases
R-HSA-8951664	Neddylation
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 77 (showing top): GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, chr15q23, YYCATTCAWW_UNKNOWN, TGGAAA_NFAT_Q4_01, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_PEPTIDASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_DN, GOBP_PROTEIN_DENEDDYLATION, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_DENEDDYLASE_ACTIVITY

GO Biological Process (4): protein deneddylation (GO:0000338), proteolysis (GO:0006508), protein deubiquitination (GO:0016579), post-translational protein modification (GO:0043687)

GO Molecular Function (5): cysteine-type peptidase activity (GO:0008234), deNEDDylase activity (GO:0019784), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Post-translational protein modification	2
Deubiquitination	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification by small protein removal	2
protein metabolic process	1
cysteine-type deubiquitinase activity	1
protein modification process	1
peptidase activity	1
ubiquitin-like protein peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SENP8	NEDD8	Q15843	961
SENP8	SENP3	Q9H4L4	889
SENP8	UBA3	Q8TBC4	792
SENP8	UBE2M	P61081	774
SENP8	UBE2F	Q969M7	771
SENP8	SUMO1	P55856	760
SENP8	CUL2	Q13617	743
SENP8	NAE1	Q13564	742
SENP8	SUMO2	P55855	731
SENP8	CUL1	Q13616	730
SENP8	UCHL3	P15374	716
SENP8	SENP1	Q9P0U3	684
SENP8	CUL4A	Q13619	679
SENP8	DCUN1D1	Q96GG9	657
SENP8	SENP7	Q9BQF6	651

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CUL1	RBX1	psi-mi:“MI:0194”(cleavage reaction)	0.980
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.790
CHN2	SENP8	psi-mi:“MI:0915”(physical association)	0.560
NEDD8	SENP8	psi-mi:“MI:0407”(direct interaction)	0.440
RPL11	SENP8	psi-mi:“MI:0569”(deneddylation reaction)	0.440
SENP8	HDGFL3	psi-mi:“MI:0915”(physical association)	0.400
SENP8	NSF	psi-mi:“MI:0915”(physical association)	0.400
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
CHN2	SENP8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): CUL1 (Biochemical Activity), PLA2G2A (Biochemical Activity), CUL4A (Biochemical Activity), CUL1 (Biochemical Activity), NEDD8 (Biochemical Activity), CUL2 (Biochemical Activity), TERF1 (Biochemical Activity), SENP8 (Affinity Capture-MS), HDGFRP3 (Affinity Capture-MS), SENP8 (Affinity Capture-Western), UBE2M (Biochemical Activity), CRBN (Dosage Growth Defect), NEDD8 (Biochemical Activity), SENP8 (Two-hybrid), HSPA4 (Biochemical Activity)

ESM2 similar proteins: A2X0Q3, B2RYG6, D3ZVK1, E1BMF7, E1BPX4, F4IDS7, I0IUP3, O00233, P42285, P45974, Q05B57, Q0IH43, Q0V9Q6, Q29FC9, Q2T9S3, Q32Q05, Q4VSI4, Q567B1, Q5F310, Q5F3A6, Q5M8L0, Q5R407, Q5VVQ6, Q6A4J8, Q6GM65, Q6U7I1, Q6YXZ7, Q7TQI3, Q7ZV00, Q84WC6, Q8AVL0, Q8CB27, Q8L5U0, Q921X6, Q92353, Q93009, Q949Y0, Q96FW1, Q96LD8, Q9CR00

Diamond homologs: Q54XR2, Q5FVJ8, Q96LD8, Q9D2Z4, Q9LSS7, Q94F30

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

465 predictions. Top by Δscore:

Variant	Effect	Δscore
15:72116575:GGAT:G	donor_gain	1.0000
15:72117674:TCTTA:T	donor_loss	0.9900
15:72117675:CTTA:C	donor_loss	0.9900
15:72117676:TTA:T	donor_loss	0.9900
15:72117677:TA:T	donor_loss	0.9900
15:72117678:A:AG	donor_loss	0.9900
15:72139310:A:G	acceptor_gain	0.9800
15:72139574:TAG:T	acceptor_gain	0.9800
15:72139575:A:AG	acceptor_gain	0.9800
15:72139575:A:C	acceptor_gain	0.9800
15:72139576:G:GG	acceptor_gain	0.9800
15:72139576:G:T	acceptor_gain	0.9800
15:72114521:A:T	donor_gain	0.9700
15:72116576:GAT:G	donor_gain	0.9700
15:72116584:A:T	donor_gain	0.9700
15:72117673:GTCTT:G	donor_loss	0.9700
15:72139572:TCTAG:T	acceptor_gain	0.9700
15:72139573:CTAGC:C	acceptor_gain	0.9700
15:72139576:GCT:G	acceptor_gain	0.9700
15:72139576:GCTC:G	acceptor_gain	0.9700
15:72139576:GCTCT:G	acceptor_gain	0.9700
15:72117678:A:AC	donor_gain	0.9600
15:72117679:C:CC	donor_gain	0.9600
15:72117679:CCT:C	donor_gain	0.9600
15:72116540:G:GT	donor_gain	0.9500
15:72116583:G:GT	donor_gain	0.9500
15:72114345:G:GT	donor_gain	0.9400
15:72114539:TCAAG:T	donor_loss	0.9400
15:72114540:CAAGG:C	donor_loss	0.9400
15:72114541:AAG:A	donor_loss	0.9400

AlphaMissense

1424 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:72139930:T:A	W103R	0.999
15:72139930:T:C	W103R	0.999
15:72139932:G:C	W103C	0.999
15:72139932:G:T	W103C	0.999
15:72139933:A:C	S104R	0.999
15:72139935:T:A	S104R	0.999
15:72139935:T:G	S104R	0.999
15:72139699:T:A	W26R	0.998
15:72139699:T:C	W26R	0.998
15:72139896:T:A	N91K	0.998
15:72139896:T:G	N91K	0.998
15:72139927:C:G	H102D	0.998
15:72140219:G:T	R199M	0.998
15:72140220:G:C	R199S	0.998
15:72140220:G:T	R199S	0.998
15:72139709:A:C	D29A	0.997
15:72139709:A:T	D29V	0.997
15:72139922:G:A	G100E	0.997
15:72139929:C:A	H102Q	0.997
15:72139929:C:G	H102Q	0.997
15:72140113:G:T	G164W	0.997
15:72140114:G:A	G164E	0.997
15:72140219:G:C	R199T	0.997
15:72139703:T:A	L27H	0.996
15:72139708:G:C	D29H	0.996
15:72139723:T:C	F34L	0.996
15:72139724:T:C	F34S	0.996
15:72139725:T:A	F34L	0.996
15:72139725:T:G	F34L	0.996
15:72139922:G:T	G100V	0.996

dbSNP variants (sampled 300 via entrez): RS1000065849 (15:72117631 G>A,C,T), RS1000263203 (15:72117341 G>A), RS1000290751 (15:72124785 G>A,C), RS1000372070 (15:72132403 T>A), RS1000647940 (15:72126734 A>T), RS1000650953 (15:72138437 C>T), RS1000772923 (15:72143921 A>G), RS1000786400 (15:72118380 C>A,T), RS1000892991 (15:72126277 C>G), RS1001070342 (15:72118541 G>A,T), RS1001157747 (15:72130829 C>T), RS1001224163 (15:72131357 T>C), RS1001273514 (15:72130856 C>G,T), RS1001339488 (15:72117082 T>C), RS1001345311 (15:72125854 C>T)

Disease associations

OMIM: gene MIM:608659 | 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
GCST001823_21	Metabolite levels (HVA/MHPG ratio)	2.000000e-06
GCST010083_289	Hemoglobin levels	1.000000e-14
GCST90013407_88	Liver enzyme levels (gamma-glutamyl transferase)	4.000000e-21

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005131	HVA measurement
EFO:0005133	MHPG measurement
EFO:0004509	hemoglobin measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741207 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,477 (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
CHEMBL165790	IPRIFLAVONE	2	5,477

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — C48: Ulp1 endopeptidase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
ST074946	Inhibition	7.8	pIC50

Binding affinities (BindingDB)

881 measured of 1023 human assays (1075 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Ethyl 5-Amino-3-(4-methoxyphenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate	EC50	0.0145 nM
4-methoxy-N-(6-methoxy-4H-indeno[1,2-d][1,3]thiazol-2-yl)benzamide	IC50	23 nM
4-(2-hydroxyethyl)-7-methyl-8a-oxidanyl-2,3-dihydro-1,4-benzoxazin-6-one	IC50	23 nM
cid_349435	IC50	40.8 nM
MLS000064750	IC50	113 nM
MLS000111651	IC50	124 nM
3-[(E)-5’-(2-Cyano-ethylsulfanyl)-5,4’-dimethyl-[2,2’]bi[[1,3]dithiolylidene]-4-ylsulfanyl]-propionitrile	IC50	129 nM
3-(2-Chloro-acetyl)-8-methyl-1,2,3,3a,4,5-hexahydro-3,10b-diaza-acephenanthrylen-6-one	IC50	348 nM
methyl 2-{3-[(methoxycarbonyl)hydrazono]-2,3-dihydro-1H-inden-1-ylidene}hydrazinecarboxylate	IC50	365 nM
4-(5-phenyl-1,3-oxazol-2-yl)benzamide	EC50	403 nM
2-(2-chlorophenyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole	EC50	431 nM
8-fluoranylindolo[2,1-b]quinazoline-6,12-dione	IC50	433 nM
MLS000585839	IC50	453 nM
SMR000549781	IC50	528 nM
cid_8379104	IC50	543 nM
MLS-0454431.0001	IC50	619 nM
MLS000581513	EC50	702 nM
SMR000186252	IC50	707 nM
5-[(4-methyl-2-nitro-phenoxy)methyl]-3-(2-thienyl)-1,2,4-oxadiazole	EC50	769 nM
3,4-dimethoxy-6,7-dihydro-[1,3]dioxolo[4,5-g]pyrido[2,1-a]isoquinolin-5-ylium	IC50	770 nM
5-bromanyl-N-(2,3-dihydro-1H-inden-5-yl)thiophene-2-carboxamide	EC50	772 nM
2-(2-bromophenyl)-5-[(2-fluorophenyl)sulfanylmethyl]-1,3,4-oxadiazole	EC50	818 nM
(6E)-6-[6-amino-4-(ethylamino)-1H-1,3,5-triazin-2-ylidene]-4-chloro-1-cyclohexa-2,4-dienone	EC50	847 nM
(2-phenyl-5,6,7,8-tetrahydrobenzothiopheno[2,3-d]pyrimidin-4-yl)amine	EC50	873 nM
2-[1-(4-methoxyanilino)ethylidene]indene-1,3-dione	EC50	889 nM
MLS000548752	EC50	907 nM
3-[[(4E)-4-(2,4-dimethylphenyl)sulfonylimino-1-keto-2-naphthyl]amino]benzoic acid	IC50	919 nM
Primaquine bisphosphate	IC50	935 nM
N’-[(E)-[4-(diethylamino)-6-oxocyclohexa-2,4-dien-1-ylidene]methyl]-2-methylfuran-3-carbohydrazide	IC50	942 nM
cid_49852505	IC50	944 nM
MLS001197729	IC50	950 nM
4-({(4Z)-1-oxo-4-[(phenylsulfonyl)imino]-1,4-dihydronaphthalen-2-yl}amino)benzoic acid	IC50	967 nM
2-[(E)-2-(4-methylphenyl)ethenyl]-1H-quinazolin-4-one	IC50	999 nM
MLS000767219	IC50	1010 nM
3-(5-p-cumenyltetrazol-2-yl)propionic acid	EC50	1040 nM
N-(6-butyl-1,3-benzothiazol-2-yl)-3-chlorothiophene-2-carboxamide	IC50	1060 nM
5-bromanyl-N-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)thiophene-2-carboxamide	EC50	1070 nM
MLS000533921	EC50	1090 nM
4-{5-[(2,4-dichlorophenoxy)methyl]-1,2,4-oxadiazol-3-yl}pyridine	EC50	1120 nM
2-[(2-fluorobenzyl)thio]-5-(4-methylphenyl)-1,3,4-oxadiazole	EC50	1140 nM
(6Z)-6-[3-[(E)-2-(4-methoxyphenyl)ethenyl]-2H-1,2,4-oxadiazol-5-ylidene]cyclohexa-2,4-dien-1-one	IC50	1190 nM
Furan-2-carboxylic acid (6-chloro-benzothiazol-2-yl)-amide	EC50	1190 nM
MLS000590115	IC50	1210 nM
MLS001181024	IC50	1220 nM
N-(1,3-benzothiazol-2-yl)-3-chlorothiophene-2-carboxamide	IC50	1220 nM
MLS-0454414.0001	IC50	1250 nM
SMR000269364	IC50	1260 nM
2-[(2-fluorobenzyl)thio]-5-(2-methylphenyl)-1,3,4-oxadiazole	EC50	1270 nM
2-(4-methylphenyl)-6-nitro-indazole	EC50	1290 nM
cid_6532818	IC50	1290 nM

ChEMBL bioactivities

293 potent at pChembl≥5 of 695 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.61	IC50	244	nM	CHEMBL3196451
6.49	IC50	325	nM	CHEMBL1506796
6.39	IC50	403	nM	CHEMBL1421255
6.34	IC50	458	nM	CHEMBL1967857
6.33	IC50	471	nM	CHEMBL1475128
6.28	IC50	520	nM	CHEMBL1870914
6.26	IC50	548	nM	CHEMBL3195102
6.26	IC50	543	nM	CHEMBL1316867
6.22	IC50	607	nM	CHEMBL595840
6.22	IC50	606	nM	CHEMBL1418096
6.21	IC50	619	nM	CHEMBL1870914
6.21	IC50	620	nM	CHEMBL1891588
6.18	IC50	660	nM	CHEMBL1316867
6.17	IC50	672	nM	CHEMBL1879394
6.15	IC50	710	nM	CHEMBL1891206
6.11	IC50	782	nM	CHEMBL1988780
6.11	IC50	770	nM	CHEMBL1884442
6.10	IC50	794	nM	CHEMBL1869875
6.09	IC50	810	nM	CHEMBL1871228
6.08	IC50	824	nM	CHEMBL1480814
6.08	IC50	830	nM	CHEMBL1884495
6.06	IC50	865	nM	CHEMBL1469807
6.06	IC50	869	nM	CHEMBL1586985
6.05	IC50	888	nM	CHEMBL1380580
6.05	IC50	884	nM	CHEMBL281980
6.05	IC50	899	nM	CHEMBL1402456
6.03	IC50	944	nM	CHEMBL1871228
6.00	IC50	990	nM	CHEMBL1869393
5.97	IC50	1060	nM	CHEMBL1869393
5.97	IC50	1080	nM	CHEMBL1302779
5.95	IC50	1130	nM	CHEMBL281980
5.95	IC50	1120	nM	CHEMBL1525161
5.93	IC50	1184	nM	CHEMBL340701
5.92	IC50	1190	nM	CHEMBL1577231
5.92	IC50	1200	nM	CHEMBL1319405
5.91	IC50	1220	nM	CHEMBL1891206
5.90	IC50	1250	nM	CHEMBL1877777
5.89	IC50	1290	nM	CHEMBL1319405
5.89	IC50	1300	nM	CHEMBL1885269
5.89	IC50	1300	nM	CHEMBL1577231
5.88	IC50	1330	nM	CHEMBL3191962
5.86	IC50	1380	nM	CHEMBL1998302
5.85	IC50	1420	nM	CHEMBL1483649
5.85	IC50	1400	nM	CHEMBL1878061
5.84	IC50	1440	nM	CHEMBL1901952
5.83	IC50	1490	nM	CHEMBL1890591
5.82	IC50	1530	nM	CHEMBL1475128
5.82	IC50	1500	nM	CHEMBL1421255
5.82	IC50	1500	nM	CHEMBL1877777
5.81	IC50	1560	nM	CHEMBL1582654

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	5
trichostatin A	affects cotreatment, decreases expression	3
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Potassium Chloride	decreases expression, decreases response to substance	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Dronabinol	decreases expression, decreases response to substance	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 6 functional, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738243	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of inhibitors of Sentrin-specific proteases (SENPs) using a Luminescent Interference Counterscreen assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2540, AID25	PubChem BioAssay data set
CHEMBL3239929	Binding	Inhibition of human DEN1 using Nedd8-EKL as substrate at 31 uM	X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases. — J Med Chem

Clinical trials (associated diseases)

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