Details of Drug Off-Target (DOT)

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

• DOT Name: SUZ domain-containing protein 1 (SZRD1)
• Synonyms: Putative MAPK-activating protein PM18/PM20/PM22
• Gene Name: SZRD1
• Related Disease:
  Advanced cancer
  Cervical cancer
  Cervical carcinoma
  Neoplasm
  Squamous cell carcinoma
• UniProt ID: SZRD1_HUMAN
• Pfam ID: PF12752 ; PF12901
• Sequence:
  MEDEEVAESWEEAADSGEIDRRLEKKLKITQKESRKSKSPPKVPIVIQDDSLPAGPPPQI
  RILKRPTSNGVVSSPNSTSRPTLPVKSLAQREAEYAEARKRILGSASPEEEQEKPILDRP
  TRISQPEDSRQPNNVIRQPLGPDGSQGFKQRR

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Cervical cancer	DISFSHPF	Definitive	Biomarker	[1]
Cervical carcinoma	DIST4S00	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SUZ domain-containing protein 1 (SZRD1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of SUZ domain-containing protein 1 (SZRD1).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of SUZ domain-containing protein 1 (SZRD1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SUZ domain-containing protein 1 (SZRD1).	[14]

10 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 SUZ domain-containing protein 1 (SZRD1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SUZ domain-containing protein 1 (SZRD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SUZ domain-containing protein 1 (SZRD1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SUZ domain-containing protein 1 (SZRD1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SUZ domain-containing protein 1 (SZRD1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of SUZ domain-containing protein 1 (SZRD1).	[8]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of SUZ domain-containing protein 1 (SZRD1).	[9]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of SUZ domain-containing protein 1 (SZRD1).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of SUZ domain-containing protein 1 (SZRD1).	[4]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of SUZ domain-containing protein 1 (SZRD1).	[13]

References

• [1] SZRD1 is a Novel Protein that Functions as a Potential Tumor Suppressor in Cervical Cancer.J Cancer. 2017 Jul 14;8(11):2132-2141. doi: 10.7150/jca.18806. eCollection 2017.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [9] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [10] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.