DCUN1D1

Summary

DCUN1D1 (defective in cullin neddylation 1 domain containing 1, HGNC:18184) is a protein-coding gene on chromosome 3q26.33, encoding DCN1-like protein 1 (Q96GG9). Part of an E3 ubiquitin ligase complex for neddylation.

Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation and regulation of protein ubiquitination. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex.

Source: NCBI Gene 54165 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 26 total
• Druggable target: yes
• MANE Select transcript: NM_020640

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18184
Approved symbol	DCUN1D1
Name	defective in cullin neddylation 1 domain containing 1
Location	3q26.33
Locus type	gene with protein product
Status	Approved
Aliases	RP42, SCRO, DCUN1L1, Tes3, SCCRO
Ensembl gene	ENSG00000043093
Ensembl biotype	protein_coding
OMIM	605905
Entrez	54165

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000292782, ENST00000460412, ENST00000466812, ENST00000469954, ENST00000487822, ENST00000492563, ENST00000497606, ENST00000632685, ENST00000925547, ENST00000925548

RefSeq mRNA: 2 — MANE Select: NM_020640 NM_001308101, NM_020640

CCDS: CCDS3240, CCDS77862

Canonical transcript exons

ENST00000292782 — 7 exons

Exon	Start	End
ENSE00001812456	182938074	182945173
ENSE00001956067	182980487	182980538
ENSE00003467431	182963881	182964049
ENSE00003521638	182947238	182947334
ENSE00003522108	182947550	182947632
ENSE00003535143	182965537	182965753
ENSE00003683481	182961226	182961356

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6884 / max 686.2134, expressed in 1765 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45773	12.5342	1729
45774	2.2080	1183
45775	1.1335	659
45776	0.4774	218
45777	0.3351	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.78	gold quality
right testis	UBERON:0004534	98.47	gold quality
sperm	CL:0000019	97.68	gold quality
testis	UBERON:0000473	96.87	gold quality
endothelial cell	CL:0000115	95.83	gold quality
tendon of biceps brachii	UBERON:0008188	95.62	gold quality
trabecular bone tissue	UBERON:0002483	94.49	gold quality
adult organism	UBERON:0007023	93.84	gold quality
male germ cell	CL:0000015	93.52	gold quality
tendon	UBERON:0000043	93.44	gold quality
esophagus squamous epithelium	UBERON:0006920	93.36	gold quality
buccal mucosa cell	CL:0002336	92.95	gold quality
calcaneal tendon	UBERON:0003701	92.56	gold quality
cauda epididymis	UBERON:0004360	92.40	gold quality
middle temporal gyrus	UBERON:0002771	92.18	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.09	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.01	gold quality
bone marrow	UBERON:0002371	91.73	gold quality
squamous epithelium	UBERON:0006914	91.55	gold quality
amniotic fluid	UBERON:0000173	91.39	gold quality
oral cavity	UBERON:0000167	91.38	gold quality
corpus callosum	UBERON:0002336	91.24	gold quality
superficial temporal artery	UBERON:0001614	91.07	gold quality
caput epididymis	UBERON:0004358	91.00	gold quality
medial globus pallidus	UBERON:0002477	90.98	gold quality
bone marrow cell	CL:0002092	90.86	gold quality
epithelium of esophagus	UBERON:0001976	90.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.61	gold quality
visceral pleura	UBERON:0002401	90.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.50	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	4208.69
E-GEOD-134144	yes	32.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

327 targeting DCUN1D1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 20)

• Loss of SCRO expression in primary adrenocortical carcinoma is associated with worse outcome and may be a marker of progressive dedifferentiation in these tumors. (PMID:15657565)
• SCCRO regulates Gli1–a key regulator of the hedgehog (HH) pathway. (PMID:17018598)
• SCCRO recruits Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin neddylation (PMID:18826954)
• SCCRO-induced invasion involves activation of MMP2 transcription in an AP2- and p53-dependent manner. (PMID:18980971)
• The GG genotype of the DCUN1D1 rs4859147 Single Nucleotide Polymorphism represents a risk factor for the development of frontotemporal lobar degeneration , increasing the risk of about fourfold. (PMID:19473369)
• a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1, thereby regulating hDCNL1-dependent activation of the cullin-RING E3 ubiquitin ligases in selected cellular compartments. (PMID:21813641)
• Distinct preferences of UBC12 and UBE2F peptides for inhibiting different DCNLs, including the oncogenic DCNL1. (PMID:23201271)
• substrate engagement prompts DCNL1 recruitment that facilitates the initiation of CUL2 neddylation and define DCNL1 as a “substrate sensor switch” for ECV activation. (PMID:23401859)
• SCCRO3 functions as a tumor suppressor by antagonizing the neddylation activity of SCCRO (PMID:25349211)
• The ubiquitin-associated (UBA) domain of SCCRO/DCUN1D1 protein serves as a feedback regulator of biochemical and oncogenic activity. (PMID:25411243)
• We also found that both miR-195 and DCUN1D1 siRNAs can inhibit cell invasion possibly through downregulating Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) at the post-transcriptional level, which can be attenuated by restoring the expression of DCUN1D1 (PMID:28791411)
• the DCN1-UBC12 interaction is inhibited by DI-591, a high-affinity, cell-permeable small-molecule inhibitor that binds to purified recombinant human DCN1 and DCN2 proteins with K i values of 10-12 nM (PMID:29074978)
• SCRO has potential to become a new target for the treatment of PC (PMID:29077169)
• Expression of DCUN1D1 in laryngeal squamous cell carcinoma and its inhibiting effect on TU-177 cells after interfered by RNA (PMID:29164666)
• DCUN1D1 activated the FAK oncogenic signaling pathway and up-regulated PD-L1. (PMID:30528265)
• ubiquitin-associated (UBA) domain-containing DCNL1 is monoubiquitylated when bound to CRLs and that this monoubiquitylation depends on the CRL-associated Ariadne RBR ligases TRIAD1 (ARIH2) and HHARI (ARIH1) and strictly requires the DCNL1’s UBA domain. (PMID:30587576)
• REVIEW: Targeting DCN1-UBC12 Protein-Protein Interaction for Regulation of Neddylation Pathway (PMID:31898237)
• Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in squamous cell lung cancer. (PMID:33862557)
• Circ-DTL sponges miR-758-3p to accelerate cervical cancer malignant progression by regulating DCUN1D1 expression. (PMID:37522575)
• DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway. (PMID:37566052)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcun1d1	ENSDARG00000099642
mus_musculus	Dcun1d1	ENSMUSG00000027708
mus_musculus	Tes3-ps	ENSMUSG00000113255
rattus_norvegicus	Dcun1d1	ENSRNOG00000012734
drosophila_melanogaster	SCCRO	FBGN0036510
drosophila_melanogaster	SCCRO4	FBGN0036967
caenorhabditis_elegans		WBGENE00010428

Paralogs (4): DCUN1D4 (ENSG00000109184), DCUN1D5 (ENSG00000137692), DCUN1D2 (ENSG00000150401), DCUN1D3 (ENSG00000188215)

Protein

Protein identifiers

DCN1-like protein 1 — Q96GG9 (reviewed: Q96GG9)

Alternative names: DCUN1 domain-containing protein 1, Defective in cullin neddylation protein 1-like protein 1, Squamous cell carcinoma-related oncogene

All UniProt accessions (6): C9J0B2, C9J8R4, C9JRU6, C9JVE2, Q96GG9, F8WC32

UniProt curated annotations — full annotation on UniProt →

Function. Part of an E3 ubiquitin ligase complex for neddylation. Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes. Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity. Also acts as an oncogene facilitating malignant transformation and carcinogenic progression.

Subunit / interactions. Part of an E3 complex for neddylation composed of cullins, RBX1, UBE2M and CAND1. Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. Binds neddylated CUL1. Interacts (via the C-terminus 50 AA) directly with RBX1. Interacts (via DCUN1 domain) with the N-terminally acetylated form of UBE2M and UBE2F. Interacts preferentially with UBE2M-NEDD8 thioester (via N-terminus 1-26 AA) than with free UBE2M. UBE2M N-terminal acetylation increases the affinity of this interaction by about 2 orders of magnitude. Interacts with CAND1; this interaction is indirect and is bridged by cullins such as CUL1 and CUL3. May also interact with regulators or subunits of cullin-RING ligases such as RNF7, ELOB and DDB1; these interactions are bridged by cullins. Component of VCB complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation. Interacts with VHL; this interaction triggers engagement of HIF1A in the VCB complex and is independent of CUL2. Interacts with CUL2 independently of VHL. Interacts with SOCS1 and SOCS2. Interacts with HIF1A; this interaction increases the interaction between VHL and DCUN1D1. Interacts (via UBA-like domain) with ARIH2; promotes DCUN1D1 ubiquitination.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in pancreas, kidney, placenta, brain and heart. Weakly or not expressed in liver, skeletal muscle and lung. Strongly overexpressed in thyroid tumors, bronchioloalveolar carcinomas, and malignant tissues of squamous cell carcinoma of the oral tongue. Not overexpressed in aggressive adrenocortical carcinomas.

Post-translational modifications. Mono- and poly-ubiquitinated by ARIH2 and ARIH1. Monoubiquitination by ARIH2 is mediated by an interaction between autoubiquitinated ARIH2 and the UBA-like domain. The monoubiquitinated form preferentially interacts with non-neddylated cullins and modulates cullin RING ligase (CRL) complex composition and activity.

Domain organisation. The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D1-cullin and DCUN1D1-E2 interaction affinities. The UBA-like domain mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin ligation to DCUN1D1.

RefSeq proteins (2): NP_001295030, NP_065691* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005176	PONY_dom	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR014764	DCN-prot	Family
IPR042460	DCN1-like_PONY	Homologous_superfamily

Pfam: PF03556, PF14555

UniProt features (35 total): helix 11, mutagenesis site 9, strand 6, sequence conflict 3, domain 2, chain 1, turn 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
6BG3	X-RAY DIFFRACTION	1.05
6BG5	X-RAY DIFFRACTION	1.1
5V86	X-RAY DIFFRACTION	1.37
6P5V	X-RAY DIFFRACTION	1.4
3TDU	X-RAY DIFFRACTION	1.5
7KWA	X-RAY DIFFRACTION	1.57
5V88	X-RAY DIFFRACTION	1.6
6P5W	X-RAY DIFFRACTION	1.69
3TDZ	X-RAY DIFFRACTION	2
5V83	X-RAY DIFFRACTION	2
6XOO	X-RAY DIFFRACTION	2.06
6XOP	X-RAY DIFFRACTION	2.07
6XOQ	X-RAY DIFFRACTION	2.07
6XOM	X-RAY DIFFRACTION	2.1
6B5Q	X-RAY DIFFRACTION	2.16
6XOL	X-RAY DIFFRACTION	2.39
5UFI	X-RAY DIFFRACTION	2.58
6XON	X-RAY DIFFRACTION	2.8
8OR3	ELECTRON MICROSCOPY	2.9
4P5O	X-RAY DIFFRACTION	3.11
8OR2	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GG9-F1	92.36	0.82

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): 115 (essential for interaction with ube2m)

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (9):

Position	Phenotype
211	loss of interaction with cul1, cul2, cul3, cula4, cula5 cand1 and rbx1; when associated with r-235 and a-241. does not a
235	loss of interaction with cul1, cul2, cul3, cula4, cula5 cand1 and rbx1; when associated with a-211 and a-241. does not a
241	loss of interaction with cul1, cul2, cul3, cula4, cula5 cand1 and rbx1; when associated with a-211 and r-235. does not a
241	loss of binding to cand1 and cul-rbx1 complex but retains binding to ube2m.
15	loss of ubiquitin binding; when associated with a-16, a-44 and a-45.
16	loss of ubiquitin binding; when associated with a-15, a-44 and a-45.
44	loss of ubiquitin binding; when associated with a-15, a-16 and a-45.
45	loss of ubiquitin binding; when associated with a-15, a-16 and a-44.
115	loss of ability to stimulate cullin neddylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 221 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_NEDDYLATION, TGACCTY_ERR1_Q2, HNF1_Q6, chr3q26, MARTINEZ_RB1_TARGETS_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, PARK_HSC_VS_MULTIPOTENT_PROGENITORS_UP, TAATGTG_MIR323

GO Biological Process (4): regulation of protein ubiquitination (GO:0031396), protein neddylation (GO:0045116), regulation of protein neddylation (GO:2000434), positive regulation of protein neddylation (GO:2000436)

GO Molecular Function (4): ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin-like protein binding (GO:0032182), cullin family protein binding (GO:0097602), protein binding (GO:0005515)

GO Cellular Component (5): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

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
cellular anatomical structure	3
regulation of protein modification by small protein conjugation or removal	2
protein neddylation	2
protein binding	2
protein ubiquitination	1
protein modification by small protein conjugation	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of protein neddylation	1
ubiquitin-like protein conjugating enzyme binding	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCUN1D1	UBE2M	P61081	997
DCUN1D1	NEDD8	Q15843	959
DCUN1D1	CUL1	Q13616	944
DCUN1D1	RBX1	P62877	927
DCUN1D1	NKX2-4	Q9H2Z4	900
DCUN1D1	UBE2F	Q969M7	860
DCUN1D1	UBA3	Q8TBC4	778
DCUN1D1	RNF7	Q9UBF6	770
DCUN1D1	NKX2-1	P43699	734
DCUN1D1	CUL3	Q13618	724
DCUN1D1	NAE1	Q13564	721
DCUN1D1	SENP8	Q96LD8	657
DCUN1D1	CAND1	Q86VP6	642
DCUN1D1	COPS5	Q92905	576
DCUN1D1	CUL5	Q93034	576

IntAct

110 interactions, top by confidence:

A	B	Type	Score
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
CUL1	UBE2M	psi-mi:“MI:0915”(physical association)	0.790
DAZAP2	DCUN1D1	psi-mi:“MI:0915”(physical association)	0.780
DCUN1D1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.780
DCUN1D1	UBE2M	psi-mi:“MI:0915”(physical association)	0.740
ARRDC3	DCUN1D1	psi-mi:“MI:0915”(physical association)	0.720
LZTS2	DCUN1D1	psi-mi:“MI:0915”(physical association)	0.720
DCUN1D1	LZTS2	psi-mi:“MI:0915”(physical association)	0.720
DCUN1D1	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
DCUN1D1	TRIM39	psi-mi:“MI:0915”(physical association)	0.700
TRIM39	DCUN1D1	psi-mi:“MI:0915”(physical association)	0.670
DCUN1D1	TRIM39	psi-mi:“MI:0915”(physical association)	0.670
DCUN1D1	CUL1	psi-mi:“MI:0914”(association)	0.670
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
CUL3	ENC1	psi-mi:“MI:0914”(association)	0.640
CUL3	DCUN1D3	psi-mi:“MI:0914”(association)	0.580
DCUN1D1	TP53BP2	psi-mi:“MI:0915”(physical association)	0.560
DCUN1D1	TRIM54	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (447): DCUN1D1 (Co-crystal Structure), DCUN1D1 (Two-hybrid), DCUN1D1 (Two-hybrid), TRIM39 (Two-hybrid), TRIM54 (Two-hybrid), ARRDC3 (Two-hybrid), VPS37B (Two-hybrid), LZTS2 (Two-hybrid), UBC (Reconstituted Complex), UBC (Affinity Capture-Western), AURKB (Reconstituted Complex), RHOA (Reconstituted Complex), UBE2M (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CAND1 (Reconstituted Complex)

ESM2 similar proteins: A8E4L1, D2K759, F1QH17, O46404, O70133, P0DI19, P35614, P35615, P62495, P62496, P62497, P62498, P83870, P83871, Q0VCX5, Q0WMV8, Q0WWE3, Q15691, Q3ZBD9, Q49B96, Q5R4C7, Q5R7Z5, Q5U2Q7, Q5XIT1, Q5ZKU1, Q5ZLC7, Q61166, Q61187, Q64143, Q66HR2, Q66T82, Q68FK8, Q6IRE4, Q6PER3, Q6V291, Q76EZ2, Q7RTV0, Q7Z7K0, Q7ZYA7, Q8BWY3

Diamond homologs: A4IHK8, Q1RMX9, Q4V8B2, Q54GP1, Q5ADL9, Q5E9V1, Q5PPL2, Q5R9G1, Q5RDF9, Q5RHX6, Q5ZKU1, Q60YT5, Q6C0B6, Q6DFA1, Q6PH85, Q86JM4, Q8BZJ7, Q8CCA0, Q8IWE4, Q8K0V2, Q8T8S1, Q92564, Q96GG9, Q9BTE7, Q9CXV9, Q9QZ73, Q9U3C8, Q9VUQ8, Q9VWB1, P0CN06, P0CN07, Q9MBG8, Q4PF67, Q5AWS1, Q8WZK4, Q12395, Q750Y3, Q6FJR2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NEDD4	“up-regulates quantity”	DCUN1D1	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
Neddylation	9	14.7×	1e-06
Antigen processing: Ubiquitination & Proteasome degradation	8	10.3×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	48.9×	5e-07
G1/S transition of mitotic cell cycle	6	27.4×	1e-05
Wnt signaling pathway	5	11.3×	4e-03
protein ubiquitination	12	11.3×	2e-07
ubiquitin-dependent protein catabolic process	6	10.1×	2e-03
DNA damage response	6	7.3×	8e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	6	7.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

26 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	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1103 predictions. Top by Δscore:

Variant	Effect	Δscore
3:182947232:CATTA:C	donor_loss	1.0000
3:182947233:ATTAC:A	donor_loss	1.0000
3:182947234:TTAC:T	donor_loss	1.0000
3:182947235:TA:T	donor_loss	1.0000
3:182947236:A:AG	donor_loss	1.0000
3:182947237:C:A	donor_loss	1.0000
3:182947237:CCTT:C	donor_gain	1.0000
3:182947330:TGTTC:T	acceptor_gain	1.0000
3:182947333:TC:T	acceptor_gain	1.0000
3:182947333:TCC:T	acceptor_loss	1.0000
3:182947334:CC:C	acceptor_gain	1.0000
3:182947335:C:CC	acceptor_gain	1.0000
3:182947339:T:C	acceptor_gain	1.0000
3:182947339:T:TC	acceptor_gain	1.0000
3:182961220:TCTTA:T	donor_loss	1.0000
3:182961221:CTTAC:C	donor_loss	1.0000
3:182961222:TTA:T	donor_loss	1.0000
3:182961223:TAC:T	donor_loss	1.0000
3:182961224:A:AC	donor_gain	1.0000
3:182961224:A:C	donor_loss	1.0000
3:182961225:C:CC	donor_gain	1.0000
3:182961228:AAT:A	donor_gain	1.0000
3:182961352:CACAT:C	acceptor_gain	1.0000
3:182961354:CAT:C	acceptor_gain	1.0000
3:182961355:ATC:A	acceptor_loss	1.0000
3:182961356:TC:T	acceptor_loss	1.0000
3:182961357:C:CC	acceptor_gain	1.0000
3:182961363:CG:C	acceptor_gain	1.0000
3:182961364:G:GC	acceptor_gain	1.0000
3:182961364:G:T	acceptor_gain	1.0000

AlphaMissense

1750 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:182945145:A:C	F243L	1.000
3:182945145:A:T	F243L	1.000
3:182945146:A:G	F243S	1.000
3:182945147:A:G	F243L	1.000
3:182945151:A:C	D241E	1.000
3:182945151:A:T	D241E	1.000
3:182945152:T:A	D241V	1.000
3:182945152:T:C	D241G	1.000
3:182945152:T:G	D241A	1.000
3:182945153:C:A	D241Y	1.000
3:182945153:C:G	D241H	1.000
3:182945153:C:T	D241N	1.000
3:182945155:A:C	I240S	1.000
3:182945155:A:T	I240N	1.000
3:182945158:A:G	L239P	1.000
3:182945158:A:T	L239H	1.000
3:182945161:A:T	V238D	1.000
3:182945164:G:A	P237L	1.000
3:182945164:G:C	P237R	1.000
3:182945164:G:T	P237H	1.000
3:182945165:G:A	P237S	1.000
3:182945165:G:T	P237T	1.000
3:182945166:C:A	W236C	1.000
3:182945166:C:G	W236C	1.000
3:182945167:C:G	W236S	1.000
3:182945168:A:G	W236R	1.000
3:182945168:A:T	W236R	1.000
3:182945170:G:A	A235V	1.000
3:182945170:G:T	A235E	1.000
3:182947238:C:G	G234R	1.000

dbSNP variants (sampled 300 via entrez): RS1000117400 (3:182983600 C>A,T), RS1000153757 (3:182979974 G>C), RS1000207386 (3:182947013 G>A), RS1000213410 (3:182955849 G>C), RS1000224837 (3:182979705 A>G), RS1000250031 (3:182987831 C>T), RS1000265758 (3:182955978 G>C), RS1000373493 (3:182941998 T>C), RS1000403156 (3:182942520 T>C), RS1000424450 (3:182941685 A>G), RS1000492690 (3:182974410 A>G), RS1000502411 (3:182974071 C>G), RS1000545763 (3:182954402 T>G), RS1000707117 (3:182940533 A>C), RS1000739631 (3:182940562 AT>A)

Disease associations

OMIM: gene MIM:605905 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003158_3	Subjective response to lithium treatment	9.000000e-07
GCST003922_1	Parkinson’s disease	3.000000e-08
GCST003984_7	Parkinson’s disease	3.000000e-14
GCST012046_3	Fasting insulin	8.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4105838 (SINGLE PROTEIN), CHEMBL4523603 (PROTEIN-PROTEIN INTERACTION)

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

Binding affinities (BindingDB)

575 measured of 913 human assays (913 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-3-[[[(E)-prop-1-enyl]sulfonylamino]methyl]-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(1R)-2-(cyanoamino)-1-hydroxyethyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[2-(cyanoamino)ethyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-(4-morpholin-4-ylbut-2-ynoylamino)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-[(1S)-1-(2-methylprop-2-enoylamino)ethyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methyl]-1-methyl-3,6-dihydro-2H-pyridine-5-carboxamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-[(E)-5-(methylamino)-5-oxopent-3-enyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(1R)-1-[cyano(methyl)amino]ethyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-(but-2-ynoylamino)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-3-[(prop-1-en-2-ylsulfonylamino)methyl]-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[cyano(2-fluoroethyl)amino]methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-[(4-morpholin-4-ylbut-2-ynoylamino)methyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(E)-5-(dimethylamino)-5-oxopent-3-enyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl 2-[[(4R,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylcarbamoyl]cyclopentene-1-carboxylate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[2-[(3,3-difluoropyrrolidin-1-yl)methyl]prop-2-enoylamino]methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[[(4R,5R)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methyl]-1-methyl-2,5-dihydropyrrole-3-carboxamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[1-(cyanoamino)cyclopropyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[cyano(methyl)amino]methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(2R)-2-cyanopyrrolidine-1-carbonyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[2-[(3,3-difluoroazetidin-1-yl)methyl]prop-2-enoylamino]methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(cyanomethylamino)methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(cyanoamino)methyl]-4-cyclopropyl-7-ethyl-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(E)-4-[3-(dimethylamino)propylamino]-4-oxobut-2-enyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
3-cyano-N-[[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methyl]oxetane-3-carboxamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[(2R)-2-chloropropanoyl]amino]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl 3-[[(4S,5R)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylcarbamoyl]but-3-enoate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl (E)-4-[[(4R,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylamino]-2-methyl-4-oxobut-2-enoate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-(2-carbamoylprop-2-enyl)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4R,5S)-7-ethyl-4-(4-fluorophenyl)-3-[[2-(hydroxymethyl)prop-2-enoylamino]methyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl (E)-4-[[(4S,5R)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylamino]-3-methyl-4-oxobut-2-enoate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4R,5S)-7-ethyl-4-(4-fluorophenyl)-3-[[2-(methoxymethyl)prop-2-enoylamino]methyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(1,1-dioxo-3H-1,2-thiazol-2-yl)methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-[[2-(methoxymethyl)prop-2-enoylamino]methyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methyl]bicyclo[1.1.0]butane-1-carboxamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-[[2-(hydroxymethyl)prop-2-enoylamino]methyl]-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[[(E)-4-(dimethylamino)but-2-enoyl]-methylamino]methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(E)-4-[2-(dimethylamino)ethylamino]-4-oxobut-2-enyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl 2-[[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylcarbamoyl]cyclobutene-1-carboxylate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[(2S)-2-chloro-2-fluoroacetyl]amino]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[[[(E)-but-2-enoyl]amino]methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(E)-5-amino-5-oxopent-3-enyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
(E)-5-[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]pent-2-enoic acid	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4S,5S)-3-[(1S)-2-(cyanoamino)-1-hydroxyethyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl 4-[[(4R,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylamino]-2-methylidene-4-oxobutanoate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
N-[(4R,5S)-3-[[cyano(methyl)amino]methyl]-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-4,5-dihydropyrazolo[5,4-b]pyridin-5-yl]-3-(trifluoromethyl)benzamide	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl 2-[[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]methylcarbamoyl]cyclopentene-1-carboxylate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF
methyl (E)-4-[[(4S,5S)-7-ethyl-4-(4-fluorophenyl)-6-oxo-1-phenyl-5-[[3-(trifluoromethyl)benzoyl]amino]-4,5-dihydropyrazolo[5,4-b]pyridin-3-yl]amino]-4-oxobut-2-enoate	IC50	600 nM	US-20250163057: DCN-1 MODULATING COMPOUNDS AND METHODS OF USE THEREOF

ChEMBL bioactivities

711 potent at pChembl≥5 of 830 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.65	IC50	2.25	nM	CHEMBL5076401
8.59	Ki	2.57	nM	CHEMBL6160376
8.54	IC50	2.86	nM	CHEMBL5075399
8.53	IC50	2.96	nM	CHEMBL6160376
8.39	Kd	4.1	nM	CHEMBL4128590
8.37	IC50	4.3	nM	CHEMBL5908146
8.27	IC50	5.36	nM	CHEMBL5070367
8.27	IC50	5.41	nM	CHEMBL6147339
8.26	IC50	5.48	nM	CHEMBL5091659
8.24	Kd	5.7	nM	CHEMBL4129669
8.21	IC50	6.15	nM	CHEMBL5092564
8.17	Kd	6.7	nM	CHEMBL4127438
8.17	IC50	6.8	nM	CHEMBL5994790
8.11	IC50	7.85	nM	CHEMBL6159903
8.09	Kd	8.1	nM	CHEMBL4129556
8.08	Kd	8.3	nM	CHEMBL4128753
8.08	Ki	8.26	nM	CHEMBL5085822
8.06	IC50	8.77	nM	CHEMBL6159780
8.03	IC50	9.37	nM	CHEMBL5086499
8.03	IC50	9.42	nM	CHEMBL6169886
8.03	IC50	9.39	nM	CHEMBL6152670
8.02	IC50	9.55	nM	CHEMBL5085822
7.98	IC50	10.57	nM	CHEMBL6148513
7.96	IC50	11.07	nM	CHEMBL5082310
7.96	IC50	11	nM	CHEMBL5268493
7.94	IC50	11.48	nM	CHEMBL5078162
7.92	IC50	12.16	nM	CHEMBL5089618
7.92	Ki	12	nM	CHEMBL4517307
7.91	IC50	12.4	nM	CHEMBL5091608
7.91	Ki	12.4	nM	CHEMBL4517307
7.91	IC50	12.31	nM	CHEMBL6151309
7.89	IC50	12.82	nM	CHEMBL6160640
7.87	Ki	13.66	nM	CHEMBL4592844
7.87	IC50	13.41	nM	CHEMBL5085047
7.85	IC50	14.06	nM	CHEMBL6147763
7.83	IC50	14.8	nM	CHEMBL5591297
7.82	IC50	15	nM	CHEMBL5276248
7.82	IC50	15.27	nM	CHEMBL6091989
7.80	IC50	15.71	nM	CHEMBL4592844
7.80	IC50	16	nM	CHEMBL5267017
7.80	IC50	15.65	nM	CHEMBL6149459
7.77	IC50	17.14	nM	CHEMBL5074683
7.77	IC50	17	nM	CHEMBL5279467
7.75	IC50	18	nM	CHEMBL4067795
7.75	IC50	18	nM	CHEMBL5801181
7.74	IC50	18.31	nM	CHEMBL4592844
7.72	IC50	19	nM	CHEMBL4517307
7.72	IC50	18.91	nM	CHEMBL6148881
7.70	IC50	19.92	nM	CHEMBL6168999
7.68	IC50	20.82	nM	CHEMBL4517307

PubChem BioAssay actives

439 with measured affinity, of 814 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
4-(1-methyltetrazol-5-yl)sulfanyl-2-prop-2-ynylsulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0003	uM
4-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-2-(naphthalen-2-ylmethylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0022	uM
2-[(4-methylphenyl)methylsulfanyl]-4-(1-methyltetrazol-5-yl)sulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0029	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-3-(6-chloro-1,3-benzothiazol-2-yl)-2-(propanoylamino)propanoyl]amino]-2-cyclopentylacetyl]amino]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]hexanamide	1494388: Binding affinity to biotin labeled recombinant N-terminal His6-tagged human DCN1 (58 to 259 residues) expressed in Escherichia coli Rosetta2 cells by biolayer interferometry analysis	kd	0.0041	uM
methyl 4-[[5-cyano-4-(1,3-thiazol-2-ylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidin-2-yl]sulfanylmethyl]benzoate	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0054	uM
2-[(3-methylphenyl)methylsulfanyl]-4-(1,3-thiazol-2-ylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0055	uM
(2S)-2-[[(2S)-2-[[(2S)-3-(6-chloro-1,3-benzothiazol-2-yl)-2-(propanoylamino)propanoyl]amino]-2-cyclopentylacetyl]amino]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-6-(dimethylamino)hexanamide	1494388: Binding affinity to biotin labeled recombinant N-terminal His6-tagged human DCN1 (58 to 259 residues) expressed in Escherichia coli Rosetta2 cells by biolayer interferometry analysis	kd	0.0057	uM
4-(1-methyltetrazol-5-yl)sulfanyl-2-(naphthalen-2-ylmethylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0062	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-3-(6-chloro-1,3-benzothiazol-2-yl)-2-(propanoylamino)propanoyl]amino]-2-(oxan-4-yl)acetyl]amino]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]hexanamide	1494388: Binding affinity to biotin labeled recombinant N-terminal His6-tagged human DCN1 (58 to 259 residues) expressed in Escherichia coli Rosetta2 cells by biolayer interferometry analysis	kd	0.0067	uM
(2S)-6-amino-N-benzhydryl-2-[[(2S)-2-[[(2S)-3-(6-chloro-1,3-benzothiazol-2-yl)-2-(propanoylamino)propanoyl]amino]-2-cyclopentylacetyl]amino]hexanamide	1494388: Binding affinity to biotin labeled recombinant N-terminal His6-tagged human DCN1 (58 to 259 residues) expressed in Escherichia coli Rosetta2 cells by biolayer interferometry analysis	kd	0.0081	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-3-(6-chloro-1,3-benzothiazol-2-yl)-2-(propanoylamino)propanoyl]amino]-2-cyclopentylacetyl]amino]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]hexanamide	1494388: Binding affinity to biotin labeled recombinant N-terminal His6-tagged human DCN1 (58 to 259 residues) expressed in Escherichia coli Rosetta2 cells by biolayer interferometry analysis	kd	0.0083	uM
2-[(4-chlorophenyl)methylsulfanyl]-4-(1-methyltetrazol-5-yl)sulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821114: Binding affinity to DCN1 (unknown origin) assessed as inhibitory constant	ki	0.0083	uM
4-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-2-[(4-methylphenyl)methylsulfanyl]-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0094	uM
2-[5-[[2-[(4-chlorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0110	uM
2-[(3-methylphenyl)methylsulfanyl]-4-(1-methyltetrazol-5-yl)sulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0111	uM
2-[(4-tert-butylphenyl)methylsulfanyl]-4-(1,3-thiazol-2-ylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0115	uM
(2S)-N-[(1S)-1-cyclohexyl-2-(3-morpholin-4-ylpropanoylamino)ethyl]-2-(propanoylamino)-3-(6-propan-2-yl-1,3-benzothiazol-2-yl)propanamide	1960619: Binding affinity to DCN1 (unknown origin) assessed as inhibition of constant by fluorescence polarization assay	ki	0.0120	uM
4-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-2-[[3-(trifluoromethyl)phenyl]methylsulfanyl]-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0122	uM
4-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-2-[(3-methylphenyl)methylsulfanyl]-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0124	uM
4-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-2-[(4-methoxyphenyl)methylsulfanyl]-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0134	uM
4-(4-methylphenyl)-2-prop-2-ynylsulfanyl-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1599581: Binding affinity to N-terminal GST tagged recombinant human DCN1 (58 to 259 residues) expressed in Escherichia coli BL21(DE3) assessed as reduction in DCN1-FAM-labelled N-terminal acetylated UBE2M (1 to 21 residues) protein-protein interaction after 30 mins by HTRF assay	ki	0.0137	uM
2-[5-[[2-[(4-bromophenyl)methylsulfanyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	2098746: Inhibition of DCN1 (unknown origin) by TR-FRET analysis	ic50	0.0148	uM
2-[5-[[2-[(4-bromophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0150	uM
2-[5-[[2-[(4-fluorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0160	uM
2-[5-[[2-[(4-chloro-3-fluorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0170	uM
4-(3,4-dimethoxyphenyl)-2-[(4-methylphenyl)methylsulfanyl]-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0171	uM
1-benzyl-3-naphthalen-2-yl-1-(1-pentan-2-ylpiperidin-4-yl)urea	1469623: Inhibition of biotin-labeled DCN1 (unknown origin) assessed as reduction in protein interaction with Ac-UBE2M12-AlexaFluor488 after 1 hr by TR-FRET assay	ic50	0.0180	uM
(2S)-N-[(1R)-1-cyclohexyl-2-(3-morpholin-4-ylpropanoylamino)ethyl]-2-(propanoylamino)-3-(6-propan-2-yl-1,3-benzothiazol-2-yl)propanamide	1758786: Inhibition of recombinant human His-tagged DCN1 (58 to 259 residues) expressed in Escherichia coli BL21 (DE3) assessed as reduction in DCN1/UBC12 interaction incubated for 30 mins by fluorescence polarization assay	ic50	0.0208	uM
4-(4-methylphenyl)-2-[(4-methylphenyl)methylsulfanyl]-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0209	uM
4-(4-methoxyphenyl)-2-[(4-methylphenyl)methylsulfanyl]-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0212	uM
2-[5-[(2-benzylsulfanyl-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0220	uM
2-[5-[[2-[(3-chloro-4-fluorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0220	uM
5-(2-phenylphenyl)-3-[[5-(2-phenylphenyl)-1H-1,2,4-triazol-3-yl]disulfanyl]-1H-1,2,4-triazole	1758787: Inhibition of recombinant human His-tagged DCN1 (58 to 259 residues) expressed in Escherichia coli BL21 (DE3) using MIKLFSLKQQKKEEESAGGTK-biotin as substrate incubated for 30 mins by HTRF assay	ki	0.0229	uM
N,N-dimethyl-2-[5-[[5-methyl-2-[(2-nitrophenyl)methylsulfanyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]ethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0240	uM
2-[(4-chlorophenyl)methylsulfanyl]-4-(1,3-thiazol-2-ylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0247	uM
2-[(4-chlorophenyl)methylsulfanyl]-4-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0253	uM
4-(1-methyltetrazol-5-yl)sulfanyl-2-[[3-(trifluoromethyl)phenyl]methylsulfanyl]-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0258	uM
4-(4-bromophenyl)-2-[(4-methylphenyl)methylsulfanyl]-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0279	uM
N-[2-[[(1-pentan-2-ylpiperidin-4-yl)-[[3-(trifluoromethyl)phenyl]carbamoyl]amino]methyl]phenyl]prop-2-enamide	1960618: Inhibition of biotinylated DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by TR-FRET analysis	ic50	0.0280	uM
2-[5-[[2-[(4-methoxyphenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride	1960673: Inhibition of GST-tagged DCN1 PONY domain (unknown origin)/human N-terminal acetylated UBC12 (1 to 12 residues) protein-protein interaction incubated for 1 hr by HTRF analysis	ic50	0.0280	uM
2-benzylsulfanyl-4-[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0281	uM
2-benzylsulfanyl-4-(1,3-thiazol-2-ylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0282	uM
4-(1-methyltetrazol-5-yl)sulfanyl-2-[[4-(trifluoromethyl)phenyl]methylsulfanyl]-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0291	uM
4-(1,3-thiazol-2-ylsulfanyl)-2-[[3-(trifluoromethyl)phenyl]methylsulfanyl]-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0293	uM
2-[(4-methoxyphenyl)methylsulfanyl]-4-(1-methyltetrazol-5-yl)sulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0312	uM
(2S)-6-amino-N-benzhydryl-2-[[(2S)-2-[[(2S)-3-(1,3-benzothiazol-2-yl)-2-(propanoylamino)propanoyl]amino]-2-cyclopentylacetyl]amino]hexanamide	1494388: Binding affinity to biotin labeled recombinant N-terminal His6-tagged human DCN1 (58 to 259 residues) expressed in Escherichia coli Rosetta2 cells by biolayer interferometry analysis	kd	0.0318	uM
(2S)-6-amino-N-benzhydryl-2-[[(2S)-2-cyclopentyl-2-[[(2S)-3-naphthalen-2-yl-2-(propanoylamino)propanoyl]amino]acetyl]amino]hexanamide	1494387: Displacement of (S)-N1-((19S,22S)-26-Amino-19-carbamoyl-1-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)-1,13,21-trioxo-5,8,11-trioxa-2,14,20-triazahexacosan-22-yl)-2-((2S,5S,8S,11S,14S,17S,20S,23S,26S)-2-(3-amino-3-oxopropyl)-5,20-bis(4-aminobutyl)-14-benzyl-23-((S)-sec-butyl)-11-(hydroxymethyl)-8,17-diisobutyl-26-(naphthalen-2-ylmethyl)-4,7,10,13,16,19,22,25,28-nonaoxo-3,6,9,12,15,18,21,24,27-nonaazanonacosanamido)pentanediamide from recombinant N-terminal His6-tagged human DCN1 (58 to 259 residues) expressed in Escherichia coli Rosetta2 cells after 30 mins by fluorescence polarization assay	ki	0.0363	uM
2-benzylsulfanyl-4-(1-methyltetrazol-5-yl)sulfanyl-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0364	uM
2-(naphthalen-2-ylmethylsulfanyl)-4-(1,3-thiazol-2-ylsulfanyl)-6-(3,4,5-trimethoxyphenyl)pyrimidine-5-carbonitrile	1821108: Inhibition of GST-tagged DCN1 (unknown origin) using AcUBE2M1-21 incubated for 30 mins by HTRF assay	ic50	0.0364	uM
4-(4-chlorophenyl)-2-prop-2-ynylsulfanyl-6-(1,3-thiazol-2-ylsulfanyl)pyrimidine-5-carbonitrile	1599580: Binding affinity to N-terminal His6-tagged recombinant human DCN1 expressed in Escherichia coli BL21-AI assessed as reduction in DCN1-FAM-labelled N-terminal acetylated UBE2M (1 to 12 residues) protein-protein interaction after 30 mins by fluorescence polarization competitive binding assay	ic50	0.0366	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, increases expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	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, increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Demecolcine	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	decreases expression	1
Thimerosal	increases expression	1
Urethane	increases expression	1
Vincristine	increases expression	1
Metribolone	decreases expression	1
Aflatoxin B1	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases methylation	1
beta-Naphthoflavone	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

165 unique, capped per target: 165 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4024549	Binding	Inhibition of biotin-labeled DCN1 (unknown origin) assessed as reduction in protein interaction with Ac-UBE2M12-AlexaFluor488 after 1 hr by TR-FRET assay	Discovery of an Orally Bioavailable Inhibitor of Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation. — J Med Chem

Clinical trials (associated diseases)

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