Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ08VCZ)

• DOT Name: Splicing factor ESS-2 homolog (ESS2)
• Synonyms: DiGeorge syndrome critical region 13; DiGeorge syndrome critical region 14; DiGeorge syndrome protein H; DGS-H; Protein ES2
• Gene Name: ESS2
• Related Disease:
  Neoplasm
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colon adenocarcinoma
  Head and neck cancer
  Head and neck carcinoma
  Prostate cancer
  Prostate carcinoma
  Cervical carcinoma
  Hepatocellular carcinoma
  Schizophrenia
  Chronic kidney disease
  Glioblastoma multiforme
• UniProt ID: ESS2_HUMAN
• PDB ID: 8C6J
• Pfam ID: PF09751
• Sequence:
  METPGASASSLLLPAASRPPRKREAGEAGAATSKQRVLDEEEYIEGLQTVIQRDFFPDVE
  KLQAQKEYLEAEENGDLERMRQIAIKFGSALGKMSREPPPPYVTPATFETPEVHAGTGVV
  GNKPRPRGRGLEDGEAGEEEEKEPLPSLDVFLSRYTSEDNASFQEIMEVAKERSRARHAW
  LYQAEEEFEKRQKDNLELPSAEHQAIESSQASVETWKYKAKNSLMYYPEGVPDEEQLFKK
  PRQVVHKNTRFLRDPFSQALSRCQLQQAAALNAQHKQGKVGPDGKELIPQESPRVGGFGF
  VATPSPAPGVNESPMMTWGEVENTPLRVEGSETPYVDRTPGPAFKILEPGRRERLGLKMA
  NEAAAKNRAKKQEALRRVTENLASLTPKGLSPAMSPALQRLVSRTASKYTDRALRASYTP
  SPARSTHLKTPASGLQTPTSTPAPGSATRTPLTQDPASITDNLLQLPARRKASDFF
• Function: May be involved in pre-mRNA splicing.
• Tissue Specificity: Highly expressed in heart, brain and skeletal muscle. Detected at low levels in placenta.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Colon adenocarcinoma	DISDRE0J	Strong	Biomarker	[1]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[4]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[6]
Schizophrenia	DISSRV2N	moderate	Biomarker	[7]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[9]

7 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 Splicing factor ESS-2 homolog (ESS2).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Splicing factor ESS-2 homolog (ESS2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Splicing factor ESS-2 homolog (ESS2).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Splicing factor ESS-2 homolog (ESS2).	[14]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Splicing factor ESS-2 homolog (ESS2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Splicing factor ESS-2 homolog (ESS2).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Splicing factor ESS-2 homolog (ESS2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Splicing factor ESS-2 homolog (ESS2).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Splicing factor ESS-2 homolog (ESS2).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Splicing factor ESS-2 homolog (ESS2).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Splicing factor ESS-2 homolog (ESS2).	[13]

References

• [1] Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme.Anticancer Agents Med Chem. 2018;18(8):1184-1196. doi: 10.2174/1871520618666180412123833.
• [2] Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells.ChemMedChem. 2019 Jul 17;14(14):1325-1328. doi: 10.1002/cmdc.201900243. Epub 2019 Jun 14.
• [3] Association of reduced kidney function with cardiovascular disease and mortality in elderly patients: comparison between the new Berlin initiative study (BIS1) and the MDRD study equations.J Nephrol. 2017 Feb;30(1):81-86. doi: 10.1007/s40620-015-0244-7. Epub 2015 Nov 16.
• [4] Volatilomic insight of head and neck cancer via the effects observed on saliva metabolites.Sci Rep. 2018 Dec 7;8(1):17725. doi: 10.1038/s41598-018-35854-x.
• [5] Optimization of diarylpentadienones as chemotherapeutics for prostate cancer.Bioorg Med Chem. 2018 Sep 1;26(16):4751-4760. doi: 10.1016/j.bmc.2018.08.018. Epub 2018 Aug 13.
• [6] Novel pyrimidine-2,4-dione-1,2,3-triazole and furo[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation.Eur J Med Chem. 2017 Jan 5;125:1247-1267. doi: 10.1016/j.ejmech.2016.11.028. Epub 2016 Nov 14.
• [7] Transmission disequilibrium test provides evidence of association between promoter polymorphisms in 22q11 gene DGCR14 and schizophrenia.J Neural Transm (Vienna). 2006 Oct;113(10):1551-61. doi: 10.1007/s00702-005-0420-3. Epub 2006 Jan 25.
• [8] Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians.Chin Med J (Engl). 2019 Mar 5;132(5):512-518. doi: 10.1097/CM9.0000000000000079.
• [9] Investigating tumor perfusion by hyperpolarized (13) C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts.Magn Reson Med. 2017 Feb;77(2):841-847. doi: 10.1002/mrm.26155. Epub 2016 Feb 19.
• [10] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [14] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [15] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.