QPCT

Summary

QPCT (glutaminyl-peptide cyclotransferase, HGNC:9753) is a protein-coding gene on chromosome 2p22.2, encoding Glutaminyl-peptide cyclotransferase (Q16769). Responsible for the biosynthesis of pyroglutamyl peptides.

This gene encodes human pituitary glutaminyl cyclase, which is responsible for the presence of pyroglutamyl residues in many neuroendocrine peptides. The amino acid sequence of this enzyme is 86% identical to that of bovine glutaminyl cyclase.

Source: NCBI Gene 25797 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 85 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_012413

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9753
Approved symbol	QPCT
Name	glutaminyl-peptide cyclotransferase
Location	2p22.2
Locus type	gene with protein product
Status	Approved
Aliases	QC, GCT
Ensembl gene	ENSG00000115828
Ensembl biotype	protein_coding
OMIM	607065
Entrez	25797

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 retained_intron

ENST00000338415, ENST00000404976, ENST00000444022, ENST00000469098, ENST00000470075, ENST00000480050, ENST00000650442, ENST00000897772, ENST00000952066, ENST00000952067, ENST00000952068

RefSeq mRNA: 1 — MANE Select: NM_012413 NM_012413

CCDS: CCDS1790

Canonical transcript exons

ENST00000338415 — 7 exons

Exon	Start	End
ENSE00001279566	37344630	37344851
ENSE00001379586	37372682	37373322
ENSE00003525758	37372356	37372472
ENSE00003545752	37367232	37367408
ENSE00003556524	37369685	37369784
ENSE00003587999	37359580	37359858
ENSE00003652840	37352789	37352935

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6792 / max 1448.3075, expressed in 1418 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19765	18.9947	1363
19764	3.6225	1061
19762	3.4815	738
19763	1.2541	514
19766	0.1157	35
19760	0.0690	16
19772	0.0684	8
19771	0.0307	8
19770	0.0244	3
19761	0.0182	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	98.61	gold quality
right adrenal gland	UBERON:0001233	98.46	gold quality
type B pancreatic cell	CL:0000169	98.18	gold quality
left adrenal gland	UBERON:0001234	98.13	gold quality
islet of Langerhans	UBERON:0000006	98.03	gold quality
adrenal cortex	UBERON:0001235	98.00	gold quality
left adrenal gland cortex	UBERON:0035825	97.88	gold quality
blood	UBERON:0000178	97.31	gold quality
adrenal gland	UBERON:0002369	97.12	gold quality
bone marrow cell	CL:0002092	96.95	gold quality
monocyte	CL:0000576	95.84	gold quality
bone marrow	UBERON:0002371	95.64	gold quality
mononuclear cell	CL:0000842	95.39	gold quality
leukocyte	CL:0000738	95.30	gold quality
upper arm skin	UBERON:0004263	94.96	gold quality
trabecular bone tissue	UBERON:0002483	94.46	gold quality
corpus epididymis	UBERON:0004359	92.73	gold quality
periodontal ligament	UBERON:0008266	92.18	gold quality
decidua	UBERON:0002450	91.61	gold quality
adrenal tissue	UBERON:0018303	91.57	gold quality
skin of hip	UBERON:0001554	90.89	gold quality
granulocyte	CL:0000094	90.30	gold quality
upper leg skin	UBERON:0004262	90.21	gold quality
penis	UBERON:0000989	90.09	gold quality
cauda epididymis	UBERON:0004360	89.94	gold quality
mammalian vulva	UBERON:0000997	89.47	gold quality
skin of leg	UBERON:0001511	89.45	gold quality
pituitary gland	UBERON:0000007	89.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.34	gold quality
zone of skin	UBERON:0000014	89.29	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	27.09
E-GEOD-135922	yes	24.01
E-GEOD-81547	yes	23.12
E-HCAD-31	yes	22.72
E-MTAB-8142	yes	22.25
E-CURD-112	yes	19.35
E-HCAD-11	yes	17.68
E-CURD-114	yes	12.93
E-GEOD-125970	yes	9.21
E-MTAB-9801	yes	9.14
E-MTAB-10553	yes	9.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, STAT5A

miRNA regulators (miRDB)

26 targeting QPCT, 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-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-618	97.62	67.46	861
HSA-MIR-3152-5P	96.98	66.88	819

Literature-anchored findings (GeneRIF, showing 26)

• Functional expression of human glutaminyl cyclase in Pichia pastoris reveals the presence of a disulfide bond with an important role in the stabilization of active protein structure. (PMID:12196024)
• human glutaminyl cyclase is a metal-dependent transferase (PMID:14522962)
• Glutaminyl cyclase was expressed as a fully active 37 kDa enzyme with kcat/Km values of 14.3, 9.3, and 2.4 mM(-1)s(-1) for the substrates Gln-Gln, Gln-NH(2), and Gln-t-butyl ester, respectively (PMID:14680951)
• Genetic variations in QPCT are important factors affecting the bone mineral density of adult women that contribute to susceptibility for osteoporosis. (PMID:15231017)
• structure of human QC in free form and bound to a substrate and three imidazole-derived inhibitors (PMID:16135565)
• Our results suggest that QPCT may be the QTL gene at chromosome 2p for spine BMD variation in the Chinese population (PMID:17687619)
• combined steady-state enzyme kinetic and X-ray structural analyses of 11 single-mutation human QCs to investigate the roles of the H-bond network in catalysis (PMID:18072935)
• The computations outline the important role of Trp329 in helping the substrate binding process and stabilizing the cyclization transition state. (PMID:18470930)
• Golgi apparatus retention implies a “housekeeping” protein maturation machinery conducting glycosylation and pyroglutamyl formation. For these isoenzymes, apparently similar strategies evolved to retain the proteins in the Golgi complex. (PMID:18486145)
• Human isoQC proteins displayed a broad substrate specificity and preference for hydrophobic substrates, similar to the related QC. (PMID:19804409)
• This study demonstrated that glutaminyl cyclase expression and pE-Abeta formation in subcortical brain regions( Edinger-Westphal nucleus, locus coeruleus and nucleus basalis Meynert) affected in Alzheimer’s disease. (PMID:20383514)
• Upon binding to PBD150, a large loop movement in gQC allows the inhibitor to be tightly held in its active site primarily by hydrophobic interactions. (PMID:21288892)
• The resilts of this studt provided histopathological evidence for QC being a prerequisite for pE-Abeta pathology in vivo and further underline the therapeutic potential of QC inhibition in Alzheimer Disease. (PMID:21301857)
• This study presents a first comparison of two mammalian QCs (human and mouse) containing typical, conserved post-translational modifications. (PMID:21671571)
• Upregulation of QPCT expression is associated with thyroid carcinomas. (PMID:23183267)
• this study demonistrated that QPCT mRNAand protein from mononuclear cells correlated with theseverity of dementia. (PMID:23207485)
• observations provide evidence for an involvement of QC in Alzheimer’s disease pathogenesis and cognitive decline by QC-catalyzed pGlu-Abeta formation (PMID:24164736)
• the genetic risk of QPCT gene for schizophrenia also exists in the Han Chinese population. (PMID:26492838)
• these findings demonstrate a significant association between common single nucleotide polymorphism within QPCT gene and schizophrenia risk in a Han Chinese population. (PMID:26572640)
• The addition of QC activity to core diagnostic CSF biomarkers may be of specific interest in clinical cases with discordant imaging and biochemical biomarker results. (PMID:28587659)
• Hydrazides Are Potent Transition-State Analogues for Glutaminyl Cyclase Implicated in the Pathogenesis of Alzheimer’s Disease. (PMID:32551535)
• A Unique Carboxylic-Acid Hydrogen-Bond Network (CAHBN) Confers Glutaminyl Cyclase Activity on M28 Family Enzymes. (PMID:33774034)
• QPCT regulation by CTCF leads to sunitinib resistance in renal cell carcinoma by promoting angiogenesis. (PMID:34036385)
• A glutaminyl cyclase-catalyzed alpha-synuclein modification identified in human synucleinopathies. (PMID:34309760)
• Clinical significance and diagnostic value of QPCT, SCEL and TNFRSF12A in papillary thyroid cancer. (PMID:37060824)
• Apicidin confers promising therapeutic effect on acute myeloid leukemia cells via increasing QPCT expression. (PMID:37381175)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	qpct	ENSDARG00000089717
mus_musculus	Qpct	ENSMUSG00000024084
rattus_norvegicus	Qpct	ENSRNOG00000005705
drosophila_melanogaster	CG6168	FBGN0036154
drosophila_melanogaster	isoQC	FBGN0036999
drosophila_melanogaster	QC	FBGN0052412
drosophila_melanogaster	CG32413	FBGN0052413
caenorhabditis_elegans		WBGENE00010418

Paralogs (1): QPCTL (ENSG00000011478)

Protein

Protein identifiers

Glutaminyl-peptide cyclotransferase — Q16769 (reviewed: Q16769)

Alternative names: Glutaminyl cyclase, Glutaminyl-tRNA cyclotransferase, Glutamyl cyclase

All UniProt accessions (4): Q16769, A0A3B3IUD5, B5MCZ9, C9JS14

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-amyloid-beta. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides.

Subcellular location. Secreted.

Similarity. Belongs to the glutaminyl-peptide cyclotransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16769-1	1	yes
Q16769-2	2

RefSeq proteins (1): NP_036545* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007484	Peptidase_M28	Domain
IPR037457	M28_QC	Domain
IPR040234	QC/QCL	Family

Pfam: PF04389

Enzyme classification (BRENDA):

• EC 2.3.2.5 — glutaminyl-peptide cyclotransferase (BRENDA: 29 organisms, 258 substrates, 720 inhibitors, 348 Km, 331 kcat entries)

Substrate kinetics (BRENDA)

145 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GLN-GLN	0.044–29.53	22
GLN-NH2	0.401–7.15	11
GLN-2-NAPHTHYLAMIDE	0.058–1.1	10
L-GLUTAMINE TERT-BUTYL ESTER	0.379–1.3	10
GLN-GLU	0.094–0.61	7
L-GLN-2-NAPHTHYLAMIDE	0.028–0.5	7
GLN-ALA	0.143–1.3	6
GLN-GLY	0.16–1.88	6
H-GLN-BETA-NAPHTHYLAMIDE	0.028–0.17	5
H-GLN-GLN-OH	0.053–1.5	5
H-GLN-GLY-OH	0.424–7.1	5
L-GLN-7-AMIDO-4-METHYLCOUMARIN	0.048–0.3	5
L-GLN-L-GLN	0.053–20.4	5
L-GLN-L-GLU	0.265–4.2	5
GLN-ARG-GLY-ILE-NH2	0.065–0.143	4

Catalyzed reactions (Rhea), 1 shown:

• N-terminal L-glutaminyl-[peptide] = N-terminal 5-oxo-L-prolyl-[peptide] + NH4(+) (RHEA:23652)

UniProt features (64 total): helix 17, mutagenesis site 15, strand 14, turn 4, sequence variant 3, binding site 3, active site 2, glycosylation site 2, signal peptide 1, chain 1, splice variant 1, disulfide bond 1

Structure

Experimental structures (PDB)

43 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2AFW	X-RAY DIFFRACTION	1.56
2AFX	X-RAY DIFFRACTION	1.64
2AFM	X-RAY DIFFRACTION	1.66
2ZEO	X-RAY DIFFRACTION	1.66
2ZEF	X-RAY DIFFRACTION	1.67
6YJY	X-RAY DIFFRACTION	1.67
2AFZ	X-RAY DIFFRACTION	1.68
2ZED	X-RAY DIFFRACTION	1.7
7CP0	X-RAY DIFFRACTION	1.7
6GBX	X-RAY DIFFRACTION	1.72
2ZEN	X-RAY DIFFRACTION	1.78
2ZEH	X-RAY DIFFRACTION	1.8
7COZ	X-RAY DIFFRACTION	1.85
6YI1	X-RAY DIFFRACTION	1.92
3PBB	X-RAY DIFFRACTION	1.95
3PBE	X-RAY DIFFRACTION	1.95
4YWY	X-RAY DIFFRACTION	1.95
8HY3	X-RAY DIFFRACTION	1.95
9FXG	X-RAY DIFFRACTION	1.96
2ZEL	X-RAY DIFFRACTION	1.97
2ZEE	X-RAY DIFFRACTION	1.99
7D8E	X-RAY DIFFRACTION	2
2ZEG	X-RAY DIFFRACTION	2.08
2ZEP	X-RAY DIFFRACTION	2.1
3SI0	X-RAY DIFFRACTION	2.1
4YU9	X-RAY DIFFRACTION	2.1
2ZEM	X-RAY DIFFRACTION	2.18
7CM0	X-RAY DIFFRACTION	2.2
2AFS	X-RAY DIFFRACTION	2.22
2AFU	X-RAY DIFFRACTION	2.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16769-F1	92.92	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 201 (proton acceptor); 248 (proton acceptor)

Ligand- & substrate-binding residues (3): 159; 202; 330

Disulfide bonds (1): 139–164

Glycosylation sites (2): 49, 296

Mutagenesis-validated functional residues (15):

Position	Phenotype
144	lowers activity by approximately 40%.
146	lowers activity by approximately 30%.
160	reduces activity by about 50%.
160	reduces activity by 96%.
201	reduces activity by about 98%.
201	abolishes activity.
207	greatly lowers activity.
248	reduces activity by 99%.
248	abolishes activity.
304	lowers activity by approximately 35%.
305	abolishes activity.
305	reduces activity by 99%.
319	reduces activity by 87%.
325	greatly lowers activity.
329	abolishes activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 273 (showing top): MODULE_52, REACTOME_INNATE_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, VICENT_METASTASIS_UP, GGGTGGRR_PAX4_03, MODULE_66, MODULE_118, MARTINEZ_RB1_TARGETS_DN, WTGAAAT_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (2): peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase (GO:0017186), protein modification process (GO:0036211)

GO Molecular Function (6): zinc ion binding (GO:0008270), glutaminyl-peptide cyclotransferase activity (GO:0016603), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872)

GO Cellular Component (5): extracellular region (GO:0005576), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular organelle lumen	2
peptidyl-glutamine modification	1
protein metabolic process	1
macromolecule modification	1
transition metal ion binding	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
transferase activity	1
cation binding	1
cellular anatomical structure	1
secretory granule lumen	1
specific granule	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

935 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
QPCT	BACE1	P56817	625
QPCT	MMEL1	Q495T6	584
QPCT	PLB1	Q6P1J6	540
QPCT	MME	P08473	509
QPCT	PSEN1	P49768	485
QPCT	CRISP1	P54107	478
QPCT	PSEN2	P49810	469
QPCT	CTSB	P07858	468
QPCT	CTSZ	Q9UBR2	462
QPCT	CRISP2	P16562	452
QPCT	APP	P05067	447
QPCT	IDE	P14735	436
QPCT	MAPT	P10636	435
QPCT	CRISP3	P54108	424
QPCT	ZFAND2B	Q8WV99	423
QPCT	NGB	Q9NPG2	423

IntAct

39 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
QPCT	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
QPCT	FRAS1	psi-mi:“MI:0915”(physical association)	0.560
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
NEDD8	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
QPCT	NUBP1	psi-mi:“MI:0914”(association)	0.350
FGR	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350
MED23	PGRMC1	psi-mi:“MI:0914”(association)	0.350
CMBL	H2BC11	psi-mi:“MI:0914”(association)	0.350
KMT5C	CBX4	psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
CFTR	MYH7B	psi-mi:“MI:0914”(association)	0.350
NUBP2	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (54): DHRS4 (Affinity Capture-MS), NUBP1 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), NUBP2 (Affinity Capture-MS), UBAP2 (Affinity Capture-MS), QPCT (Affinity Capture-MS), QPCT (Affinity Capture-MS), QPCT (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), NUBP1 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), NUBP2 (Affinity Capture-MS), QPCT (Affinity Capture-MS), QPCT (Affinity Capture-MS)

ESM2 similar proteins: A5A6K7, O17754, O54858, O75976, O89001, P04836, P14384, P15087, P15169, P16870, P21661, P23188, P23377, P28841, P29122, P37892, P38836, P42787, Q00493, Q0II73, Q16769, Q28193, Q2KIG3, Q2KJ83, Q4R4M3, Q4R7R2, Q5REC2, Q5RFD6, Q5U901, Q63415, Q66K79, Q80V42, Q8IVL8, Q8N436, Q8QGP3, Q8R4H4, Q8R4V4, Q8WXQ8, Q90240, Q96IY4

Diamond homologs: A7ISW1, A7ISW2, B7QK46, P0CV92, P43599, Q0V8G3, Q16769, Q28120, Q4R942, Q54B14, Q86PD7, Q8BH73, Q90YA8, Q9CYK2, Q9NXS2, Q9VRQ9, Q9YIB5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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	10	13.9×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	7	59.8×	7e-09
G1/S transition of mitotic cell cycle	6	28.7×	1e-05
protein ubiquitination	7	6.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1048 predictions. Top by Δscore:

Variant	Effect	Δscore
2:37369679:CCTCA:C	acceptor_loss	1.0000
2:37369680:CTCA:C	acceptor_loss	1.0000
2:37369681:TCA:T	acceptor_loss	1.0000
2:37369682:CAG:C	acceptor_loss	1.0000
2:37369683:A:AG	acceptor_gain	1.0000
2:37369683:A:AT	acceptor_loss	1.0000
2:37369683:AG:A	acceptor_gain	1.0000
2:37369684:G:GG	acceptor_gain	1.0000
2:37369684:GG:G	acceptor_gain	1.0000
2:37369781:ATTGG:A	donor_loss	1.0000
2:37369782:TTGG:T	donor_loss	1.0000
2:37369784:GGTA:G	donor_loss	1.0000
2:37369785:G:GG	donor_gain	1.0000
2:37369785:GT:G	donor_loss	1.0000
2:37369786:T:A	donor_loss	1.0000
2:37344849:AAGG:A	donor_loss	0.9900
2:37344851:GG:G	donor_loss	0.9900
2:37344852:G:T	donor_loss	0.9900
2:37344853:T:A	donor_loss	0.9900
2:37350479:G:GT	donor_gain	0.9900
2:37352787:A:AG	acceptor_gain	0.9900
2:37352788:G:GG	acceptor_gain	0.9900
2:37352932:TCAGG:T	donor_loss	0.9900
2:37352933:CAG:C	donor_loss	0.9900
2:37352934:AGG:A	donor_loss	0.9900
2:37352935:GG:G	donor_loss	0.9900
2:37352937:T:G	donor_loss	0.9900
2:37359573:T:TA	acceptor_gain	0.9900
2:37367230:A:AG	acceptor_gain	0.9900
2:37367231:G:GG	acceptor_gain	0.9900

AlphaMissense

2350 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:37359729:C:G	C139W	0.995
2:37359678:T:A	N122K	0.993
2:37359678:T:G	N122K	0.993
2:37359730:C:G	H140D	0.993
2:37367328:G:T	G215W	0.992
2:37367329:G:A	G215E	0.992
2:37372741:G:C	D334H	0.992
2:37367290:A:T	E202V	0.991
2:37359727:T:C	C139R	0.990
2:37359728:G:A	C139Y	0.990
2:37359740:C:T	S143F	0.990
2:37372445:G:C	D305H	0.990
2:37359772:T:C	F154L	0.989
2:37359774:T:A	F154L	0.989
2:37359774:T:G	F154L	0.989
2:37367281:A:T	D199V	0.989
2:37367332:C:T	S216F	0.989
2:37372448:G:C	D306H	0.989
2:37372449:A:T	D306V	0.989
2:37372461:T:C	F310S	0.989
2:37359794:C:A	A161D	0.988
2:37359804:T:G	C164W	0.988
2:37367284:G:A	G200D	0.988
2:37367284:G:T	G200V	0.988
2:37372460:T:C	F310L	0.988
2:37372462:T:A	F310L	0.988
2:37372462:T:G	F310L	0.988
2:37359637:T:C	F109L	0.987
2:37359639:C:A	F109L	0.987
2:37359639:C:G	F109L	0.987

dbSNP variants (sampled 300 via entrez): RS1000248057 (2:37343123 A>T), RS1000465135 (2:37368825 T>A), RS1000614052 (2:37348326 C>T), RS1000722771 (2:37343193 A>T), RS1001040740 (2:37346317 T>C), RS1001122793 (2:37357656 C>G), RS1001173856 (2:37368133 T>C), RS1001176376 (2:37343513 A>C), RS1001378957 (2:37345190 C>A,G,T), RS1001420801 (2:37356943 G>C,T), RS1001438739 (2:37352533 T>C), RS1001528453 (2:37363425 C>G,T), RS1001571405 (2:37351674 G>A,C), RS1001631005 (2:37362881 C>T), RS1001728224 (2:37373699 G>A,C)

Disease associations

OMIM: gene MIM:607065 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001510_5	Response to TNF-alpha inhibitors in rheumatoid arthritis	8.000000e-06
GCST002149_12	Schizophrenia	7.000000e-09
GCST002299_6	Chronic lymphocytic leukemia	9.000000e-06
GCST003468_1	Chronic lymphocytic leukemia	1.000000e-07
GCST004146_1	Chronic lymphocytic leukemia	5.000000e-08
GCST004904_221	Body mass index	3.000000e-12
GCST004904_252	Body mass index	3.000000e-09
GCST006585_502	Blood protein levels	4.000000e-28
GCST007201_18	Schizophrenia	5.000000e-07
GCST008839_521	Height	1.000000e-09
GCST011743_31	HDL cholesterol levels in HIV infection	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4508 (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: 100 (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
CHEMBL3659477	VAROGLUTAMSTAT	2	100

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M28: Aminopeptidase Y

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
QP5038	Inhibition	8.4	pIC50
BI-43	Inhibition	7.92	pIC50
varoglutamstat	Binding	7.77	pKd
SEN177	Inhibition	7.7	pKi
PBD150	Inhibition	7.22	pKi

Binding affinities (BindingDB)

413 measured of 597 human assays (600 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-(2-hydroxypropan-2-yl)benzonitrile	IC50	1 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-(2-methyl-1,3-oxazol-5-yl)benzonitrile	IC50	2 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
5-(1,3-dimethylpyrazol-4-yl)-2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)benzonitrile	IC50	2 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-(1-methylpyrazol-4-yl)benzonitrile	IC50	2 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-pyridazin-4-ylbenzonitrile	IC50	2 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluoropyrrolidin-1-yl)-2,3-difluorophenyl]-1,3-oxazolidin-2-one	KI	2.49 nM	US-9512115: Inhibitors
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluoropyrrolidin-1-yl)-2-fluorophenyl]-1,3-oxazolidin-2-one	KI	2.69 nM	US-9512115: Inhibitors
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluorobutoxy)-2,3-difluorophenyl]-1,3-oxazolidin-2-one	KI	2.9 nM	US-9512115: Inhibitors
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-pyridin-3-ylbenzonitrile	IC50	3 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-(2-methylpyrimidin-5-yl)benzonitrile	IC50	3 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-[2-(trifluoromethyl)pyrimidin-5-yl]benzonitrile	IC50	3 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
1-(3H-benzimidazol-5-yl)-5-(3-hydroxy-4-methoxyphenyl)imidazolidine-2,4-dione	IC50	3.08 nM	US-8962860: Inhibitors of glutaminyl cyclase
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluoropropoxy)-2,3-difluorophenyl]-1,3-oxazolidin-2-one	KI	3.34 nM	US-9512115: Inhibitors
1-(3H-benzimidazol-5-yl)-5-(4-propoxyphenyl)imidazolidine-2,4-dione	KI	3.8 nM	US-8962860: Inhibitors of glutaminyl cyclase
1-(3H-benzimidazol-5-yl)-5-[4-(2-cyclopropyl-1,3-thiazol-4-yl)phenyl]imidazolidine-2,4-dione	KI	4 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[4-(2-cyclopropyl-1,3-thiazol-5-yl)phenyl]imidazolidine-2,4-dione	KI	4 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[4-[2-(cyclopropylmethyl)tetrazol-5-yl]phenyl]imidazolidine-2,4-dione	KI	4 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
2-[4-fluoro-4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-(6-fluoro-3-pyridinyl)-5-(1,3,5-trimethylpyrazol-4-yl)benzonitrile	IC50	4 nM	US-20250250252: PIPERIDINYLBENZONITRILE DERIVATIVES AS INHIBITORS OF GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE AND GLUTAMINYL-PEPTIDE CYCLOTRANSFERASE LIKE PROTEIN
1-(3H-benzimidazol-5-yl)-5-(4-phenylphenyl)imidazolidine-2,4-dione	KI	4.13 nM	US-8962860: Inhibitors of glutaminyl cyclase
1-(3H-benzimidazol-5-yl)-2-[4-(1,1-dioxo-1,4-thiazinan-4-yl)phenyl]-3-methoxy-2H-pyrrol-5-one	KI	4.4 nM	US-8530670: Inhibitors
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluoropyrrolidin-1-yl)-2,6-difluorophenyl]-1,3-oxazolidin-2-one	KI	4.53 nM	US-9512115: Inhibitors
1-(3H-benzimidazol-5-yl)-2-(4-morpholin-4-ylphenyl)-3-piperidin-1-yl-2H-pyrrol-5-one	KI	4.6 nM	US-8530670: Inhibitors
1-(3H-benzimidazol-5-yl)-5-[4-(2-propyltetrazol-5-yl)phenyl]imidazolidine-2,4-dione	KI	5 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluorobutoxy)-2-fluorophenyl]-1,3-oxazolidin-2-one	KI	5.03 nM	US-9512115: Inhibitors
2-[(4S)-3-(3H-benzimidazol-5-yl)-2-oxo-1,3-oxazolidin-4-yl]-5-(3,3-difluoropyrrolidin-1-yl)benzonitrile	KI	5.15 nM	US-9512115: Inhibitors
1-(3H-benzimidazol-5-yl)-5-[4-(2-prop-2-ynyltetrazol-5-yl)phenyl]imidazolidine-2,4-dione	KI	6 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[2,3-difluoro-4-[5-(methoxymethyl)thiophen-3-yl]phenyl]imidazolidin-2-one	KI	6 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3,4-Dimethoxyphenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea	KI	6 nM	US-9656991: Inhibitors of glutaminyl cyclase
1-(3H-benzimidazol-5-yl)-5-(2,1,3-benzothiadiazol-5-yl)imidazolidine-2,4-dione	KI	6.07 nM	US-8962860: Inhibitors of glutaminyl cyclase
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(2,2-difluoropropoxy)-2,3-difluorophenyl]-1,3-oxazolidin-2-one	KI	6.21 nM	US-9512115: Inhibitors
1-(3H-benzimidazol-5-yl)-5-(4-bromo-2-fluorophenyl)-4-sulfanylideneimidazolidin-2-one	KI	6.49 nM	US-8962860: Inhibitors of glutaminyl cyclase
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(2,2-difluoropropoxy)-2,6-difluorophenyl]-1,3-oxazolidin-2-one	KI	6.66 nM	US-9512115: Inhibitors
(5S)-1-(3H-benzimidazol-5-yl)-5-[2,3-difluoro-4-[5-(trifluoromethyl)thiophen-3-yl]phenyl]imidazolidin-2-one	KI	7 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[2,3-difluoro-4-(5-methylthiophen-3-yl)phenyl]imidazolidin-2-one	KI	7 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[4-(2-propan-2-yltetrazol-5-yl)phenyl]imidazolidine-2,4-dione	KI	8 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[4-[2-(2,2,2-trifluoroethyl)tetrazol-5-yl]phenyl]imidazolidine-2,4-dione	KI	8 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluoropropoxy)-2-fluorophenyl]-1,3-oxazolidin-2-one	KI	8.5 nM	US-9512115: Inhibitors
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluorobutoxy)-3-fluorophenyl]-1,3-oxazolidin-2-one	KI	8.95 nM	US-9512115: Inhibitors
1-(3H-benzimidazol-5-yl)-5-[4-[2-(trifluoromethyl)-1,3-thiazol-5-yl]phenyl]imidazolidine-2,4-dione	KI	9 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(4,4-difluorocyclohexyl)-2-fluorophenyl]-1,3-oxazolidin-2-one	KI	9.24 nM	US-9512115: Inhibitors
(4S)-3-(3H-benzimidazol-5-yl)-4-[2-fluoro-4-(2-fluoro-2-methylpropoxy)phenyl]-1,3-oxazolidin-2-one	KI	9.83 nM	US-9512115: Inhibitors
1-(3H-benzimidazol-5-yl)-5-[4-[2-(2-methylpropyl)tetrazol-5-yl]phenyl]imidazolidine-2,4-dione	KI	10 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[4-(2-but-2-ynyltetrazol-5-yl)phenyl]imidazolidine-2,4-dione	KI	10 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
1-(3H-benzimidazol-5-yl)-5-[4-(2-pent-2-ynyltetrazol-5-yl)phenyl]imidazolidine-2,4-dione	KI	10 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
(4S)-3-(3H-benzimidazol-5-yl)-4-[4-(3,3-difluoropyrrolidin-1-yl)-3-fluorophenyl]-1,3-oxazolidin-2-one	KI	10.4 nM	US-9512115: Inhibitors
1-(3H-benzimidazol-5-yl)-5-[4-[5-(ethoxymethyl)thiophen-3-yl]-2,3-difluorophenyl]imidazolidin-2-one	KI	11 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease
5-[(4S)-3-(3H-benzimidazol-5-yl)-2-oxo-1,3-oxazolidin-4-yl]-2-(3,3-difluoropyrrolidin-1-yl)benzonitrile	KI	11.4 nM	US-9512115: Inhibitors
3-[3-(5-methylimidazol-1-yl)propyl]-2-sulfanylidene-4aH-quinazolin-4-one	KI	11.6 nM	US-9034907: Inhibitors of glutaminyl cyclase
1-(3H-benzimidazol-5-yl)-5-(4-morpholin-4-ylphenyl)pyrrolidine-2,4-dione	KI	11.9 nM	US-8530670: Inhibitors
1-(3H-benzimidazol-5-yl)-5-[4-(2-methyltetrazol-5-yl)phenyl]imidazolidine-2,4-dione	KI	12 nM	US-10584120: Benzimidazole compounds and use thereof for treating Alzheimer’s Disease or Huntington’s Disease

ChEMBL bioactivities

1205 potent at pChembl≥5 of 1315 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.28	IC50	0.053	nM	CHEMBL4462495
10.00	IC50	0.1	nM	CHEMBL5092802
9.52	IC50	0.3	nM	CHEMBL5085353
9.34	IC50	0.46	nM	CHEMBL5086776
9.30	IC50	0.5	nM	CHEMBL5085226
9.22	IC50	0.6	nM	CHEMBL5075575
9.15	IC50	0.7	nM	CHEMBL4077433
9.15	IC50	0.71	nM	CHEMBL5089771
9.10	IC50	0.8	nM	CHEMBL5083519
9.00	IC50	1	nM	CHEMBL5088732
9.00	IC50	1	nM	CHEMBL5085670
9.00	IC50	1	nM	CHEMBL6103394
9.00	IC50	1	nM	CHEMBL6163584
9.00	IC50	1	nM	CHEMBL6166421
9.00	IC50	1	nM	CHEMBL6174330
9.00	IC50	1	nM	CHEMBL6165872
9.00	IC50	1	nM	CHEMBL6161773
9.00	IC50	1	nM	CHEMBL6166839
9.00	IC50	1	nM	CHEMBL6147767
9.00	IC50	1	nM	CHEMBL6174275
9.00	IC50	1	nM	CHEMBL6168765
9.00	IC50	1	nM	CHEMBL6160352
9.00	IC50	1	nM	CHEMBL6166960
9.00	IC50	1	nM	CHEMBL6172023
8.89	IC50	1.3	nM	CHEMBL4525926
8.85	IC50	1.4	nM	CHEMBL5089285
8.82	IC50	1.5	nM	CHEMBL5081653
8.80	IC50	1.6	nM	CHEMBL4445407
8.80	IC50	1.6	nM	CHEMBL5081891
8.80	IC50	1.6	nM	CHEMBL5083687
8.77	IC50	1.7	nM	CHEMBL5081537
8.74	IC50	1.8	nM	CHEMBL4204093
8.74	IC50	1.8	nM	CHEMBL5092925
8.64	IC50	2.3	nM	CHEMBL5266674
8.64	IC50	2.3	nM	CHEMBL5279792
8.62	Ki	2.4	nM	CHEMBL6164940
8.60	Ki	2.487	nM	CHEMBL5789311
8.60	Ki	2.53	nM	CHEMBL5789311
8.59	IC50	2.6	nM	CHEMBL5094369
8.59	IC50	2.6	nM	CHEMBL5084485
8.59	Ki	2.6	nM	CHEMBL583368
8.57	IC50	2.7	nM	CHEMBL5079181
8.57	Ki	2.688	nM	CHEMBL5998031
8.55	IC50	2.8	nM	CHEMBL4464130
8.55	IC50	2.8	nM	CHEMBL5081843
8.54	Ki	2.905	nM	CHEMBL5745972
8.53	Ki	2.923	nM	CHEMBL5998031
8.52	IC50	3	nM	CHEMBL5266206
8.51	IC50	3.08	nM	CHEMBL3677287
8.49	Ki	3.24	nM	CHEMBL3677287

PubChem BioAssay actives

760 with measured affinity, of 994 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
1-(1H-indol-6-yl)-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	752868: Inhibition of human glutaminyl cyclase expressed in HEK293 cells using L-glutaminyl-beta-naphthylamine as substrate after 1 hr by fluorometric analysis	ic50	<0.0001	uM
1-[3-(5-methylimidazol-1-yl)propyl]-3-pyridin-3-ylthiourea	752868: Inhibition of human glutaminyl cyclase expressed in HEK293 cells using L-glutaminyl-beta-naphthylamine as substrate after 1 hr by fluorometric analysis	ic50	<0.0001	uM
1-[3-(5-methylimidazol-1-yl)propyl]-3-quinolin-3-ylthiourea	752868: Inhibition of human glutaminyl cyclase expressed in HEK293 cells using L-glutaminyl-beta-naphthylamine as substrate after 1 hr by fluorometric analysis	ic50	<0.0001	uM
1-isoquinolin-6-yl-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	752868: Inhibition of human glutaminyl cyclase expressed in HEK293 cells using L-glutaminyl-beta-naphthylamine as substrate after 1 hr by fluorometric analysis	ic50	<0.0001	uM
1-[3-(5-methylimidazol-1-yl)propyl]-3-quinolin-8-ylthiourea	752868: Inhibition of human glutaminyl cyclase expressed in HEK293 cells using L-glutaminyl-beta-naphthylamine as substrate after 1 hr by fluorometric analysis	ic50	<0.0001	uM
1-(2,3-dihydro-1H-inden-5-yl)-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	752868: Inhibition of human glutaminyl cyclase expressed in HEK293 cells using L-glutaminyl-beta-naphthylamine as substrate after 1 hr by fluorometric analysis	ic50	<0.0001	uM
1-(cyclopentylmethyl)-1-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0001	uM
2-fluoro-5-[2-[4-(4-methyl-1,2,4-triazol-3-yl)piperidin-1-yl]-3-pyridinyl]pyridine	2072999: Inhibition of sQC (unknown origin) expressed in Escherichia coli Transetta (DE3) assessed as N-terminal pyroglutamate formation using fluorescent substrate H-Gln-AMC incubated for 12 hrs by microplate reader	ic50	0.0001	uM
3-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-1-[3-(5-methylimidazol-1-yl)propyl]-1-propan-2-ylthiourea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0003	uM
1-(cyclopentylmethyl)-1-[3-methoxy-4-(2-piperazin-1-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0005	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-1-cyclopentyl-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0005	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-1-cyclohexyl-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0006	uM
1-[3-methoxy-4-(2-piperazin-1-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1442139: Inhibition of human glutaminyl cyclase assessed as reduction in conversion of H-Gln-AMC hydrobromide to pGlu-AMC preincubated with substrate for 10 mins followed by enzyme addition by pGAPase coupled fluorometry	ic50	0.0007	uM
1-[4-[4-(dimethylamino)butoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-(1-methylpiperidin-4-yl)urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0007	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-1-cyclobutyl-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0008	uM
1-(cyclopentylmethyl)-1-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0010	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-1-benzyl-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0010	uM
1-(3,4-dimethoxyphenyl)-1-[(4-fluorophenyl)methyl]-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1577851: Inhibition of recombinant human N-terminal His6-tagged glutaminyl cyclase (Ala33 to Leu361 residues) expressed in baculovirus infected Sf21 insect cells using H-Gln-AMC hydrobromide as substrate measured in presence of pGAPase by fluorometric assay	ic50	0.0013	uM
1-[(4-fluorophenyl)methyl]-1-[3-methoxy-4-(2-piperazin-1-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0014	uM
1-cyclohexyl-1-[3-methoxy-4-(2-piperazin-1-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0015	uM
1-[4-[2-(2-aminoethylamino)-4-pyridinyl]butyl]-1-(3,4-dimethoxyphenyl)-3-[3-(5-methylimidazol-1-yl)propyl]urea	1577851: Inhibition of recombinant human N-terminal His6-tagged glutaminyl cyclase (Ala33 to Leu361 residues) expressed in baculovirus infected Sf21 insect cells using H-Gln-AMC hydrobromide as substrate measured in presence of pGAPase by fluorometric assay	ic50	0.0016	uM
1-[4-[2-(2-amino-4-pyridinyl)ethoxy]-3-methoxyphenyl]-1-[(4-fluorophenyl)methyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0016	uM
1-[3-methoxy-4-(2-piperazin-1-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-(1-methylpiperidin-4-yl)urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0016	uM
1-[4-[2-(2-amino-4-pyridinyl)ethoxy]-3-methoxyphenyl]-1-cyclohexyl-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0017	uM
1-[4-[4-[2-(2-aminoethylamino)-4-pyridinyl]butoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1373876: Inhibition of human glutaminyl cyclase using Gln-AMC as substrate by pGAPase coupled fluorescence assay	ic50	0.0018	uM
1-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-(1-methylpiperidin-4-yl)urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0018	uM
1-(1,3-dimethylindazol-6-yl)-1-[(4-fluorophenyl)methyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1945957: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis	ic50	0.0023	uM
1-cyclohexyl-3-[3-(5-methylimidazol-1-yl)propyl]-1-(3-methyl-2H-indazol-5-yl)urea	1945957: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis	ic50	0.0023	uM
1-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-propan-2-ylurea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0026	uM
1-[(4-fluorophenyl)methyl]-1-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0026	uM
1-(3,4-dimethoxyphenyl)-N-[3-(5-methylimidazol-1-yl)propyl]cyclopropane-1-carbothioamide	438503: Inhibition of human glutaminyl cyclase expressed in Pichia pastoris by pGAP coupled enzyme assay	ki	0.0026	uM
1-cyclohexyl-1-[4-[3-(dimethylamino)propoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0027	uM
1-(3,4-dimethoxyphenyl)-3-[3-(5-methylimidazol-1-yl)propyl]-1-propan-2-ylthiourea	1577851: Inhibition of recombinant human N-terminal His6-tagged glutaminyl cyclase (Ala33 to Leu361 residues) expressed in baculovirus infected Sf21 insect cells using H-Gln-AMC hydrobromide as substrate measured in presence of pGAPase by fluorometric assay	ic50	0.0028	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-(1-methylpiperidin-4-yl)urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0028	uM
1-(1,3-dimethylindazol-5-yl)-1-[(4-fluorophenyl)methyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1945957: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis	ic50	0.0030	uM
1-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-(pyridin-3-ylmethyl)urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0032	uM
1-cyclohexyl-3-[3-(5-methylimidazol-1-yl)propyl]-1-(3-methyl-2H-indazol-6-yl)urea	1945957: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis	ic50	0.0032	uM
1-(3,4-dimethoxyphenyl)-1-[(3-fluorophenyl)methyl]-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1577851: Inhibition of recombinant human N-terminal His6-tagged glutaminyl cyclase (Ala33 to Leu361 residues) expressed in baculovirus infected Sf21 insect cells using H-Gln-AMC hydrobromide as substrate measured in presence of pGAPase by fluorometric assay	ic50	0.0034	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-1-(cyclopentylmethyl)-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0034	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-3-(3H-benzimidazol-5-ylmethyl)-1-[(4-fluorophenyl)methyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0034	uM
1-(cyclopentylmethyl)-1-(1,3-dimethylindazol-6-yl)-3-[3-(5-methylimidazol-1-yl)propyl]urea	1945957: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis	ic50	0.0034	uM
1-[(3-chlorophenyl)methyl]-1-(3,4-dimethoxyphenyl)-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1577851: Inhibition of recombinant human N-terminal His6-tagged glutaminyl cyclase (Ala33 to Leu361 residues) expressed in baculovirus infected Sf21 insect cells using H-Gln-AMC hydrobromide as substrate measured in presence of pGAPase by fluorometric assay	ic50	0.0035	uM
1-[(4-fluorophenyl)methyl]-1-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0035	uM
1-[4-[2-[4-[2-(2-aminoethoxy)ethyl]piperazin-1-yl]ethoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1373876: Inhibition of human glutaminyl cyclase using Gln-AMC as substrate by pGAPase coupled fluorescence assay	ic50	0.0036	uM
1-[4-(2-amino-4-pyridinyl)butyl]-1-(3,4-dimethoxyphenyl)-3-[3-(5-methylimidazol-1-yl)propyl]urea	1577851: Inhibition of recombinant human N-terminal His6-tagged glutaminyl cyclase (Ala33 to Leu361 residues) expressed in baculovirus infected Sf21 insect cells using H-Gln-AMC hydrobromide as substrate measured in presence of pGAPase by fluorometric assay	ic50	0.0036	uM
1-[4-[4-(2-amino-4-pyridinyl)butoxy]-3-methoxyphenyl]-1-cyclohexyl-3-[3-(5-methylimidazol-1-yl)propyl]urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0036	uM
1-[4-[4-(dimethylamino)butoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1442139: Inhibition of human glutaminyl cyclase assessed as reduction in conversion of H-Gln-AMC hydrobromide to pGlu-AMC preincubated with substrate for 10 mins followed by enzyme addition by pGAPase coupled fluorometry	ic50	0.0037	uM
1-[4-[3-[4-(2-aminoethyl)piperazin-1-yl]propoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]thiourea	1373876: Inhibition of human glutaminyl cyclase using Gln-AMC as substrate by pGAPase coupled fluorescence assay	ic50	0.0038	uM
1-[3-methoxy-4-(2-piperazin-1-ylethoxy)phenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-(pyridin-3-ylmethyl)urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0038	uM
1-[4-[2-(2-amino-4-pyridinyl)ethoxy]-3-methoxyphenyl]-3-[3-(5-methylimidazol-1-yl)propyl]-1-(1-methylpiperidin-4-yl)urea	1813084: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry	ic50	0.0038	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, decreases expression	3
Temozolomide	affects response to substance, decreases expression	2
Decitabine	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	increases expression	2
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
hydroquinone	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
clothianidin	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	affects cotreatment, increases expression	1
Arsenic	decreases expression, increases abundance	1
Carmustine	affects response to substance	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1

ChEMBL screening assays

53 unique, capped per target: 51 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1057686	Binding	Inhibition of human glutaminyl cyclase expressed in Pichia pastoris by pGAP coupled enzyme assay	Inhibitors for human glutaminyl cyclase by structure based design and bioisosteric replacement. — J Med Chem
CHEMBL6088378	Functional	In vivo inhibition of glutaminyl cyclase isoenzyme activity in tumor of human A549 cells xenografted BALB/C nude mouse model at 2 mg/kg, ip by isoQC-PAP assay	Design, synthesis, and evaluation of 4-(4-methyl-4H-1,2,4-triazol-3-yl)piperidine derivatives as potential glutaminyl cyclase isoenzyme inhibitors for the treatment of cancer. — Eur J Med Chem

Clinical trials (associated diseases)

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