Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT60XXUP)

• DOT Name: Stress-associated endoplasmic reticulum protein 1 (SERP1)
• Synonyms: Ribosome-attached membrane protein 4
• Gene Name: SERP1
• Related Disease:
  Oral mucositis
  Cardiovascular disease
  Adult glioblastoma
  Glioblastoma multiforme
  Hyperglycemia
  Matthew-Wood syndrome
  Non-insulin dependent diabetes
  Pancreatic ductal carcinoma
  Stroke
  Thyroid gland papillary carcinoma
• UniProt ID: SERP1_HUMAN
• Pfam ID: PF06624
• Sequence:
  MVAKQRIRMANEKHSKNITQRGNVAKTSRNAPEEKASVGPWLLALFIFVVCGSAIFQIIQ
  SIRMGM
• Function: Interacts with target proteins during their translocation into the lumen of the endoplasmic reticulum. Protects unfolded target proteins against degradation during ER stress. May facilitate glycosylation of target proteins after termination of ER stress. May modulate the use of N-glycosylation sites on target proteins.
• Reactome Pathway:
  Insertion of tail-anchored proteins into the endoplasmic reticulum membrane (R-HSA-9609523)
  XBP1(S) activates chaperone genes (R-HSA-381038)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral mucositis	DISS93V5	Definitive	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[3]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[4]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[5]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[4]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[5]
Stroke	DISX6UHX	Limited	Biomarker	[6]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[17]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[18]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Stress-associated endoplasmic reticulum protein 1 (SERP1).	[21]

References

• [1] Genomic features of a multidrug-resistant Enterobacter cloacae ST279 producing CTX-M-15 and AAC(6')-Ib-cr isolated from fatal infectious stomatitis in a crossed pit viper (Bothrops alternatus).J Glob Antimicrob Resist. 2018 Dec;15:290-291. doi: 10.1016/j.jgar.2018.11.009. Epub 2018 Nov 15.
• [2] The current status and future directions of myxoma virus, a master in immune evasion.Vet Res. 2011 Jun 9;42(1):76. doi: 10.1186/1297-9716-42-76.
• [3] MicroRNA-124 expression counteracts pro-survival stress responses in glioblastoma.Oncogene. 2015 Apr 23;34(17):2204-14. doi: 10.1038/onc.2014.168. Epub 2014 Jun 23.
• [4] Preliminary structural characterization and hypoglycemic effects of an acidic polysaccharide SERP1 from the residue of Sarcandra glabra.Carbohydr Polym. 2017 Nov 15;176:140-151. doi: 10.1016/j.carbpol.2017.08.071. Epub 2017 Aug 19.
• [5] SERP1 is a novel marker of poor prognosis in pancreatic ductal adenocarcinoma patients via anti-apoptosis and regulating SRPRB/NF-B axis.Int J Oncol. 2017 Oct;51(4):1104-1114. doi: 10.3892/ijo.2017.4111. Epub 2017 Aug 31.
• [6] Methods for Assessing Serpins as Neuroprotective Therapeutics.Methods Mol Biol. 2018;1826:223-235. doi: 10.1007/978-1-4939-8645-3_15.
• [7] Gene profiling identifies genes specific for well-differentiated epithelial thyroid tumors.Cell Mol Biol (Noisy-le-grand). 2005 Sep 5;51(2):177-86.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [17] 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.
• [18] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [19] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [20] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [21] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.