Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFV43FZ)

• DOT Name: Pyroglutamyl-peptidase 1 (PGPEP1)
• Synonyms: EC 3.4.19.3; 5-oxoprolyl-peptidase; Pyroglutamyl aminopeptidase I; PAP-I; Pyroglutamyl-peptidase I; PGP-I; Pyrrolidone-carboxylate peptidase
• Gene Name: PGPEP1
• UniProt ID: PGPI_HUMAN
• EC Number: 3.4.19.3
• Pfam ID: PF01470
• Sequence:
  MEQPRKAVVVTGFGPFGEHTVNASWIAVQELEKLGLGDSVDLHVYEIPVEYQTVQRLIPA
  LWEKHSPQLVVHVGVSGMATTVTLEKCGHNKGYKGLDNCRFCPGSQCCVEDGPESIDSII
  DMDAVCKRVTTLGLDVSVTISQDAGRYLCDFTYYTSLYQSHGRSAFVHVPPLGKPYNADQ
  LGRALRAIIEEMLDLLEQSEGKINYCHKH
• Function: Removes 5-oxoproline from various penultimate amino acid residues except L-proline.
• BioCyc Pathway: MetaCyc:HS05394-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Pyroglutamyl-peptidase 1 (PGPEP1).	[13]

References

• [1] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.