PGPEP1

Summary

PGPEP1 (pyroglutamyl-peptidase I, HGNC:13568) is a protein-coding gene on chromosome 19p13.11, encoding Pyroglutamyl-peptidase 1 (Q9NXJ5). Removes 5-oxoproline from various penultimate amino acid residues except L-proline.

The gene encodes a cysteine protease and member of the peptidase C15 family of proteins. The encoded protein cleaves amino terminal pyroglutamate residues from protein substrates including thyrotropin-releasing hormone and other neuropeptides. Expression of this gene may be downregulated in colorectal cancer, while activity of the encoded protein may be negatively correlated with cancer progression in colorectal cancer patients. Activity of the encoded protease may also be altered in other disease states including in liver cirrhosis, which is associated with reduced protease activity, and in necrozoospermia, which is associated with elevated protease activity.

Source: NCBI Gene 54858 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 74 total
• Druggable target: yes
• MANE Select transcript: NM_017712

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13568
Approved symbol	PGPEP1
Name	pyroglutamyl-peptidase I
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	PGP-I, Pcp, PGP, PGPI
Ensembl gene	ENSG00000130517
Ensembl biotype	protein_coding
OMIM	610694
Entrez	54858

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 nonsense_mediated_decay

ENST00000252813, ENST00000269919, ENST00000595066, ENST00000595552, ENST00000596962, ENST00000597431, ENST00000597663, ENST00000600283, ENST00000604499, ENST00000880407, ENST00000926421, ENST00000950662

RefSeq mRNA: 7 — MANE Select: NM_017712 NM_001300927, NM_001308366, NM_001329471, NM_001329476, NM_001329477, NM_001329478, NM_017712

CCDS: CCDS12375, CCDS74314, CCDS77264, CCDS82319

Canonical transcript exons

ENST00000269919 — 5 exons

Exon	Start	End
ENSE00000951782	18363391	18369950
ENSE00001511730	18340598	18340715
ENSE00003677063	18357383	18357615
ENSE00003700841	18355895	18356011
ENSE00003702352	18342859	18342911

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 94.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2843 / max 223.5125, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174644	12.6060	1789
174645	9.6783	1721

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	94.12	gold quality
renal medulla	UBERON:0000362	94.03	gold quality
tendon of biceps brachii	UBERON:0008188	93.66	gold quality
pylorus	UBERON:0001166	92.62	gold quality
inferior vagus X ganglion	UBERON:0005363	91.29	gold quality
medial globus pallidus	UBERON:0002477	91.13	gold quality
globus pallidus	UBERON:0001875	91.08	gold quality
lateral globus pallidus	UBERON:0002476	91.00	gold quality
vena cava	UBERON:0004087	90.77	silver quality
ventral tegmental area	UBERON:0002691	90.56	gold quality
subthalamic nucleus	UBERON:0001906	90.42	silver quality
hindlimb stylopod muscle	UBERON:0004252	90.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.91	silver quality
pancreatic ductal cell	CL:0002079	89.80	silver quality
apex of heart	UBERON:0002098	89.46	gold quality
substantia nigra pars compacta	UBERON:0001965	89.34	gold quality
pons	UBERON:0000988	89.23	silver quality
body of tongue	UBERON:0011876	89.18	silver quality
substantia nigra pars reticulata	UBERON:0001966	89.11	silver quality
right lobe of liver	UBERON:0001114	89.03	gold quality
adult mammalian kidney	UBERON:0000082	88.82	gold quality
mucosa of transverse colon	UBERON:0004991	88.70	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.52	gold quality
saphenous vein	UBERON:0007318	88.40	gold quality
stromal cell of endometrium	CL:0002255	88.29	gold quality
pericardium	UBERON:0002407	88.28	silver quality
superior vestibular nucleus	UBERON:0007227	88.23	gold quality
spinal cord	UBERON:0002240	88.22	gold quality
superior surface of tongue	UBERON:0007371	88.17	gold quality
pharyngeal mucosa	UBERON:0000355	87.84	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.13
E-CURD-89	no	69.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

183 targeting PGPEP1, 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-12118	100.00	65.88	1270
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6780A-5P	99.88	66.69	2776

Literature-anchored findings (GeneRIF, showing 7)

• cloning and sequencing of the human (AJ278828) pyroglutamyl-peptidase I (PMID:12651114)
• VX-710 modulates Pgp, MRP-1, and BCRP(R482), and has potential as a clinical broad-spectrum multidrug resistance modulator in malignancies. (PMID:15014037)
• The activities of pyroglutamyl peptidase I and prolyl endopeptidase in necrozoospermia were found to be higher in the corresponding soluble and particulate sperm fractions, respectively, with respect to those measured in normozoospermic semen (PMID:15380924)
• The specific reduction of the levels of pyroglutamyl-aminopeptidase activity in serum of liver cirrhosis patients might be considered as a potential candidate to be included in a combination of markers for the diagnosis of this disease. (PMID:25687677)
• cytosolic peptidases(puromycin-sensitive aminopeptidase (PSA), aminopeptidase B (APB) and pyroglutamyl-peptidase I (PGI) ) may be involved in colorectal carcinogenesis (PMID:26078706)
• Two-photon fluorogenic probe for visualizing PGP-1 activity in inflammatory tissues and serum from patients. (PMID:34816269)
• Circ-PGPEP1 augments renal cell carcinoma proliferation, Warburg effect, and distant metastasis. (PMID:37722013)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgpep1	ENSDARG00000054666
mus_musculus	Pgpep1	ENSMUSG00000056204
rattus_norvegicus	Mk1	ENSRNOG00000019657
drosophila_melanogaster	CG32147	FBGN0047178
caenorhabditis_elegans		WBGENE00008894
caenorhabditis_elegans		WBGENE00008897
caenorhabditis_elegans	M04C9.1	WBGENE00010856
caenorhabditis_elegans	M04C9.2	WBGENE00010857
caenorhabditis_elegans	M04C9.3	WBGENE00010858
caenorhabditis_elegans		WBGENE00012252
caenorhabditis_elegans		WBGENE00018056
caenorhabditis_elegans		WBGENE00018057

Paralogs (1): PGPEP1L (ENSG00000183571)

Protein

Protein identifiers

Pyroglutamyl-peptidase 1 — Q9NXJ5 (reviewed: Q9NXJ5)

Alternative names: 5-oxoprolyl-peptidase, Pyroglutamyl aminopeptidase I, Pyroglutamyl-peptidase I, Pyrrolidone-carboxylate peptidase

All UniProt accessions (7): Q9NXJ5, M0QX66, M0R0B6, M0R3H3, S4R2Y9, U3KQ24, U3KQG9

UniProt curated annotations — full annotation on UniProt →

Function. Removes 5-oxoproline from various penultimate amino acid residues except L-proline.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Activity regulation. Inhibited by transition metal ions including Ni(2+), Zn(2+), and Cu(2+) and by sulfhydryl-blocking agents.

Similarity. Belongs to the peptidase C15 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NXJ5-1	1	yes
Q9NXJ5-2	2

RefSeq proteins (7): NP_001287856, NP_001295295, NP_001316400, NP_001316405, NP_001316406, NP_001316407, NP_060182* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000816	Peptidase_C15	Family
IPR016125	Peptidase_C15-like	Family
IPR033693	PGPEP1_Glu_AS	Active_site
IPR033694	PGPEP1_Cys_AS	Active_site
IPR036440	Peptidase_C15-like_sf	Homologous_superfamily

Pfam: PF01470

Enzyme classification (BRENDA):

• EC 3.4.19.3 — pyroglutamyl-peptidase I (BRENDA: 39 organisms, 107 substrates, 128 inhibitors, 89 Km, 44 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-PYROGLUTAMYL-BETA-NAPHTHYLAMIDE	0.17–1.46	11
PYROGLUTAMYL-BETA-NAPHTHYLAMIDE	0.0208–1.79	7
L-PYROGLUTAMYL-L-ALA	0.045–0.89	4
L-PYROGLUTAMYL-P-NITROANILIDE	0.028–0.054	4
4(R)-N-(2-NITROXYETHYL)-2-OXOTHIAZOLIDINE-4-CARB	0.5–0.58	3
L-2-OXOIMIDAZOLIDINE-4-CARBOXYL-L-ALA	0.33–0.42	3
L-2-OXOOXAZOLIDINE-4-CARBOXYL-L-ALA	0.55–0.71	3
L-2-OXOTHIAZOLIDINE-4-CARBOXYL-L-ALA	0.3–0.43	3
PYROGLUTAMATE-4-METHYLCOUMARIN 7-AMIDE	0.04–0.15	3
PYROGLUTAMYL-HIS-PRO-4-METHYLCOUMARIN 7-AMIDE	0.0025–0.4198	3
THYROTROPIN-RELEASING HORMONE	0.041–0.056	3
GONADOTROPIN-RELEASING HORMONE	0.079–0.089	2
L-PYROGLUTAMYL-7-AMIDO-4-METHYLCOUMARIN	0.018–0.028	2
PYROGLUTAMYL-P-NITROANILIDE	0.73–20	2
THYROLIBERIN	0.04–0.727	2

UniProt features (5 total): active site 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXJ5-F1	93.62	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 (3): 85; 149; 168

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 288 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOZGIT_ESR1_TARGETS_DN, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY

GO Biological Process (2): proteolysis (GO:0006508), protein catabolic process (GO:0030163)

GO Molecular Function (5): pyroglutamyl-peptidase activity (GO:0016920), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
cellular anatomical structure	2
macromolecule catabolic process	1
cysteine-type peptidase activity	1
omega peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGPEP1	PREP	P48147	948
PGPEP1	TRH	P20396	919
PGPEP1	NTS	P30990	758
PGPEP1	GRP	P07491	708
PGPEP1	TRHDE	Q9UKU6	687
PGPEP1	RNPEP	Q9H4A4	671
PGPEP1	GNRH1	P01148	630
PGPEP1	LRRC25	Q8N386	619
PGPEP1	DNPEP	Q9ULA0	598
PGPEP1	APEH	P13798	589
PGPEP1	NPEPPS	P55786	511
PGPEP1	DPP4	P27487	507
PGPEP1	LAP3	P28838	486
PGPEP1	KXD1	Q9BQD3	455
PGPEP1	TGDS	O95455	447

IntAct

8 interactions, top by confidence:

A	B	Type	Score
PGPEP1	TNNT3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): GTF2I (Affinity Capture-MS), TNNT3 (Affinity Capture-MS), SELO (Affinity Capture-MS), HBB (Affinity Capture-MS), TRIM11 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), GFER (Affinity Capture-MS), SELO (Affinity Capture-MS), HBB (Affinity Capture-MS), GTF2I (Affinity Capture-MS), HBA2 (Affinity Capture-MS), TRIM11 (Affinity Capture-MS), TNNT3 (Affinity Capture-MS), GFER (Affinity Capture-MS), WDYHV1 (Two-hybrid)

ESM2 similar proteins: A4FV42, A4IG53, A4IGU3, A4QP75, A6QP81, A6QQV6, A8E7D2, B3DLB3, D9IVE5, F1QCV2, F4ZGF2, P0C5J1, P83006, Q13057, Q28CZ7, Q28IN4, Q3T0H0, Q3U3W5, Q3UZW7, Q4V9P6, Q501S4, Q502I6, Q5BLD8, Q5F389, Q5M969, Q5RE14, Q5RFM7, Q5U4E8, Q5ZIB9, Q6NTR1, Q6P4Z6, Q6PCI6, Q6QHF9, Q803A8, Q865R1, Q8BLU2, Q8C0L6, Q8MIR4, Q8N7N1, Q8R123

Diamond homologs: A6NFU8, O73944, Q76IC5, Q7NHX6, Q9CWB5, Q9ESW8, Q9NXJ5, Q838N8, P42673

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1751 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2213813:T:A	donor_gain	1.0000
16:2214134:GGAC:G	donor_loss	1.0000
16:2214135:GACC:G	donor_loss	1.0000
16:2214137:C:CA	donor_loss	1.0000
16:2214137:CCCG:C	donor_gain	1.0000
19:18340696:G:GT	donor_gain	1.0000
19:18340697:A:T	donor_gain	1.0000
19:18340714:GG:G	donor_gain	1.0000
19:18340715:GG:G	donor_gain	1.0000
19:18355890:TCCA:T	acceptor_loss	1.0000
19:18355891:CCA:C	acceptor_loss	1.0000
19:18355893:A:AG	acceptor_gain	1.0000
19:18355893:A:AT	acceptor_loss	1.0000
19:18355893:AG:A	acceptor_gain	1.0000
19:18355894:G:GA	acceptor_gain	1.0000
19:18355894:GG:G	acceptor_gain	1.0000
19:18355894:GGA:G	acceptor_gain	1.0000
19:18355894:GGAGC:G	acceptor_gain	1.0000
19:18356010:AG:A	donor_loss	1.0000
19:18356011:GG:G	donor_loss	1.0000
19:18357381:AGCT:A	acceptor_gain	1.0000
19:18357382:GCTG:G	acceptor_gain	1.0000
19:18357613:C:T	donor_gain	1.0000
19:18357613:CAGG:C	donor_loss	1.0000
19:18357616:G:GA	donor_loss	1.0000
16:2211800:C:A	donor_gain	0.9900
16:2211809:C:A	donor_gain	0.9900
16:2213728:TTA:T	donor_gain	0.9900
16:2214054:C:CA	acceptor_loss	0.9900
16:2214054:C:CC	acceptor_gain	0.9900

AlphaMissense

1359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18342861:T:C	F13L	0.999
19:18342863:T:A	F13L	0.999
19:18342863:T:G	F13L	0.999
19:18342870:T:C	F16L	0.999
19:18342872:T:A	F16L	0.999
19:18342872:T:G	F16L	0.999
19:18342894:A:C	S24R	0.998
19:18342896:T:A	S24R	0.998
19:18342896:T:G	S24R	0.998
19:18357423:T:A	V82D	0.998
19:18357432:A:T	E85V	0.998
19:18363399:G:A	C149Y	0.998
19:18363453:T:A	V167D	0.998
19:18363455:C:G	H168D	0.998
19:18342890:C:A	N22K	0.997
19:18342890:C:G	N22K	0.997
19:18342895:G:T	S24I	0.997
19:18357399:G:A	G74E	0.997
19:18357433:G:C	E85D	0.997
19:18357433:G:T	E85D	0.997
19:18357441:G:A	G88E	0.997
19:18363398:T:C	C149R	0.997
19:18363457:C:A	H168Q	0.997
19:18363457:C:G	H168Q	0.997
19:18342859:G:A	G12E	0.996
19:18355953:T:A	V49D	0.996
19:18357467:G:C	D97H	0.996
19:18363400:C:G	C149W	0.996
19:18363404:T:C	F151L	0.996
19:18363406:T:A	F151L	0.996

dbSNP variants (sampled 300 via entrez): RS1000047599 (19:18364601 G>A), RS1000080992 (19:18366474 T>C), RS1000119138 (19:18352144 T>C), RS1000152514 (19:18370385 C>T), RS1000172346 (19:18349035 A>G), RS1000199474 (19:18342229 C>T), RS1000238902 (19:18347783 G>A), RS1000272658 (19:18343293 C>T), RS1000289895 (19:18347452 C>T), RS1000344114 (19:18346919 T>C), RS1000450866 (19:18353110 G>T), RS1000532955 (19:18366122 C>T), RS1000542093 (19:18368999 T>C), RS1000772866 (19:18354617 A>T), RS1000924924 (19:18359818 T>C)

Disease associations

OMIM: gene MIM:610694 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST002127_34	Periodontitis (Mean PAL)	7.000000e-06
GCST002783_302	Body mass index	8.000000e-09
GCST002783_558	Body mass index	3.000000e-08
GCST002783_65	Body mass index	1.000000e-06
GCST003252_40	Systemic lupus erythematosus	5.000000e-06
GCST004495_73	BMI (adjusted for smoking behaviour)	5.000000e-06
GCST004497_29	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-06
GCST004904_202	Body mass index	4.000000e-12
GCST005194_110	Coronary artery disease	6.000000e-06
GCST005711_1	Growth differentiation factor-15 levels	3.000000e-35
GCST005712_1	Growth differentiation factor-15 levels (conditioned on rs888663)	1.000000e-22
GCST005712_2	Growth differentiation factor-15 levels (conditioned on rs888663)	2.000000e-10
GCST005830_107	Hand grip strength	2.000000e-11
GCST006519_1	Growth differentiation factor-15 levels	3.000000e-32
GCST006519_2	Growth differentiation factor-15 levels	8.000000e-28
GCST006697_13	Parental longevity (combined parental attained age, Martingale residuals)	9.000000e-07
GCST006802_36	Body mass index	1.000000e-06
GCST007576_93	Chronotype	4.000000e-11
GCST007927_30	Medication use (beta blocking agents)	5.000000e-08
GCST008152_95	Weight	3.000000e-06
GCST008163_124	Height	7.000000e-06
GCST008163_206	Height	2.000000e-07
GCST008832_10	Gastroesophageal reflux disease	2.000000e-10
GCST008839_23	Height	7.000000e-15
GCST010988_17	Adult body size	1.000000e-15
GCST012227_362	Hip circumference adjusted for BMI	2.000000e-11
GCST012227_363	Hip circumference adjusted for BMI	4.000000e-12
GCST90000514_27	Gastroesophageal reflux disease	2.000000e-10
GCST90020028_1484	Hip circumference adjusted for BMI	2.000000e-12
GCST90020028_1485	Hip circumference adjusted for BMI	4.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0006941	grip strength measurement
EFO:0007796	parental longevity
EFO:0008328	chronotype measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0004338	body weight
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066224 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	4
Estradiol	affects cotreatment, decreases expression, increases expression	3
bisphenol A	increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
trichostatin A	affects expression	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Calcitriol	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Plant Oils	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5512156	Binding	Inhibition of PGP-1 (unknown origin) expressed in Escherichia coli assessed as fluorescent intensity using pGA as substrate at 100 uM incubated for 12 hrs by microplate reader	X-ray Structure-Guided Discovery of a Potent Benzimidazole Glutaminyl Cyclase Inhibitor That Shows Activity in a Parkinson’s Disease Mouse Model. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer