Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG9DI66)

• DOT Name: Zinc finger protein SNAI3 (SNAI3)
• Synonyms: Protein snail homolog 3; Zinc finger protein 293
• Gene Name: SNAI3
• Related Disease:
  Adult germ cell tumor
  Adult glioblastoma
  Colorectal carcinoma
  Germ cell tumor
  Germ cell tumour
  Glioblastoma multiforme
  Non-small-cell lung cancer
  Melanoma
  Neoplasm
• UniProt ID: SNAI3_HUMAN
• Pfam ID: PF00096
• Sequence:
  MPRSFLVKTHSSHRVPNYRRLETQREINGACSACGGLVVPLLPRDKEAPSVPGDLPQPWD
  RSSAVACISLPLLPRIEEALGASGLDALEVSEVDPRASRAAIVPLKDSLNHLNLPPLLVL
  PTRWSPTLGPDRHGAPEKLLGAERMPRAPGGFECFHCHKPYHTLAGLARHRQLHCHLQVG
  RVFTCKYCDKEYTSLGALKMHIRTHTLPCTCKICGKAFSRPWLLQGHVRTHTGEKPYACS
  HCSRAFADRSNLRAHLQTHSDAKKYRCRRCTKTFSRMSLLARHEESGCCPGP
• Function: Seems to inhibit myoblast differentiation. Transcriptional repressor of E-box-dependent transactivation of downstream myogenic bHLHs genes. Binds preferentially to the canonical E-box sequences 5'-CAGGTG-3' and 5'-CACCTG-3'.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult germ cell tumor	DISJUCQ7	Strong	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Germ cell tumor	DIS62070	Strong	Altered Expression	[1]
Germ cell tumour	DISOF3TK	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Melanoma	DIS1RRCY	Limited	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]

3 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 Zinc finger protein SNAI3 (SNAI3).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Zinc finger protein SNAI3 (SNAI3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Zinc finger protein SNAI3 (SNAI3).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Zinc finger protein SNAI3 (SNAI3).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Zinc finger protein SNAI3 (SNAI3).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Zinc finger protein SNAI3 (SNAI3).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Zinc finger protein SNAI3 (SNAI3).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Zinc finger protein SNAI3 (SNAI3).	[11]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Zinc finger protein SNAI3 (SNAI3).	[10]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Zinc finger protein SNAI3 (SNAI3).	[13]

References

• [1] Identification and characterization of human SNAIL3 (SNAI3) gene in silico.Int J Mol Med. 2003 Mar;11(3):383-8.
• [2] Comparative genomics on SNAI1, SNAI2, and SNAI3 orthologs.Oncol Rep. 2005 Oct;14(4):1083-6.
• [3] FOXD4 induces tumor progression in colorectal cancer by regulation of the SNAI3/CDH1 axis.Cancer Biol Ther. 2018;19(11):1065-1071. doi: 10.1080/15384047.2018.1480291. Epub 2018 Sep 25.
• [4] MiR-940 inhibits TGF--induced epithelial-mesenchymal transition and cell invasion by targeting Snail in non-small cell lung cancer.J Cancer. 2019 Jun 2;10(12):2735-2744. doi: 10.7150/jca.31800. eCollection 2019.
• [5] Directed Dedifferentiation Using Partial Reprogramming Induces Invasive Phenotype in Melanoma Cells.Stem Cells. 2016 Apr;34(4):832-46. doi: 10.1002/stem.2284. Epub 2016 Jan 19.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [11] The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
• [12] 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.
• [13] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.