Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMWY2KV)

• DOT Name: Transcription factor HES-2 (HES2)
• Synonyms: Class B basic helix-loop-helix protein 40; bHLHb40; Hairy and enhancer of split 2
• Gene Name: HES2
• Related Disease:
  Gastric cancer
  Stomach cancer
  Neuroblastoma
• UniProt ID: HES2_HUMAN
• Pfam ID: PF07527 ; PF00010
• Sequence:
  MGLPRRAGDAAELRKSLKPLLEKRRRARINQSLSQLKGLILPLLGRENSNCSKLEKADVL
  EMTVRFLQELPASSWPTAAPLPCDSYREGYSACVARLARVLPACRVLEPAVSARLLEHLW
  RRAASATLDGGRAGDSSGPSAPAPAPASAPEPASAPVPSPPSPPCGPGLWRPW
• Function: Transcriptional repressor of genes that require a bHLH protein for their transcription.
• Tissue Specificity: Expressed in placenta, pancreatic cancer, colon cancer with RER, cervical cancer, and in head and neck tumors.
• KEGG Pathway: Human papillomavirus infection (hsa05165)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[1]
Neuroblastoma	DISVZBI4	Limited	Posttranslational Modification	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transcription factor HES-2 (HES2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor HES-2 (HES2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor HES-2 (HES2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transcription factor HES-2 (HES2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transcription factor HES-2 (HES2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Transcription factor HES-2 (HES2).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transcription factor HES-2 (HES2).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Transcription factor HES-2 (HES2).	[9]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Transcription factor HES-2 (HES2).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Transcription factor HES-2 (HES2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transcription factor HES-2 (HES2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor HES-2 (HES2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor HES-2 (HES2).	[3]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transcription factor HES-2 (HES2).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transcription factor HES-2 (HES2).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Transcription factor HES-2 (HES2).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Transcription factor HES-2 (HES2).	[15]

References

• [1] Hath1 up-regulates gastric mucin gene expression in gastric cells.Biochem Biophys Res Commun. 2006 Jun 16;344(4):1166-71. doi: 10.1016/j.bbrc.2006.03.238. Epub 2006 Apr 21.
• [2] Notch pathway activation induces neuroblastoma tumor cell growth arrest.Pediatr Blood Cancer. 2012 May;58(5):682-9. doi: 10.1002/pbc.23202. Epub 2011 Jul 8.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [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] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [10] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [11] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [14] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.