Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT51HVC4)

• DOT Name: Left-right determination factor 1 (LEFTY1)
• Synonyms: Left-right determination factor B; Protein lefty-1; Protein lefty-B
• Gene Name: LEFTY1
• Related Disease:
  Breast neoplasm
  Chronic kidney disease
  Diamond-Blackfan anemia
  Neoplasm
• UniProt ID: LFTY1_HUMAN
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MQPLWLCWALWVLPLASPGAALTGEQLLGSLLRQLQLKEVPTLDRADMEELVIPTHVRAQ
  YVALLQRSHGDRSRGKRFSQSFREVAGRFLALEASTHLLVFGMEQRLPPNSELVQAVLRL
  FQEPVPKAALHRHGRLSPRSARARVTVEWLRVRDDGSNRTSLIDSRLVSVHESGWKAFDV
  TEAVNFWQQLSRPRQPLLLQVSVQREHLGPLASGAHKLVRFASQGAPAGLGEPQLELHTL
  DLGDYGAQGDCDPEAPMTEGTRCCRQEMYIDLQGMKWAENWVLEPPGFLAYECVGTCRQP
  PEALAFKWPFLGPRQCIASETDSLPMIVSIKEGGRTRPQVVSLPNMRVQKCSCASDGALV
  PRRLQP
• Function: Required for left-right axis determination as a regulator of LEFTY2 and NODAL.
• KEGG Pathway:
  TGF-beta sig.ling pathway (hsa04350)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway:
  Regulation of signaling by NODAL (R-HSA-1433617)
  Signaling by NODAL (R-HSA-1181150)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[2]
Diamond-Blackfan anemia	DISI2SNW	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

1 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 Left-right determination factor 1 (LEFTY1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Left-right determination factor 1 (LEFTY1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Left-right determination factor 1 (LEFTY1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Left-right determination factor 1 (LEFTY1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Left-right determination factor 1 (LEFTY1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Left-right determination factor 1 (LEFTY1).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Left-right determination factor 1 (LEFTY1).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Left-right determination factor 1 (LEFTY1).	[9]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Left-right determination factor 1 (LEFTY1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Left-right determination factor 1 (LEFTY1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Left-right determination factor 1 (LEFTY1).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Left-right determination factor 1 (LEFTY1).	[12]

References

• [1] Wnt3a-dependent and -independent protein interaction networks of chromatin-bound -catenin in mouse embryonic stem cells.Mol Cell Proteomics. 2013 Jul;12(7):1980-94. doi: 10.1074/mcp.M112.026914. Epub 2013 Apr 15.
• [2] Anti-inflammatory effects of Lefty-1 in renal tubulointerstitial inflammation via regulation of the NF-B pathway.Int J Mol Med. 2018 Mar;41(3):1293-1304. doi: 10.3892/ijmm.2017.3327. Epub 2017 Dec 18.
• [3] RAP-011 improves erythropoiesis in zebrafish model of Diamond-Blackfan anemia through antagonizing lefty1.Blood. 2015 Aug 13;126(7):880-90. doi: 10.1182/blood-2015-01-622522. Epub 2015 Jun 24.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Effect of ovarian steroids on gene expression profile in human uterine microvascular endothelial cells. Fertil Steril. 2009 Aug;92(2):709-21.
• [8] Triclosan and bisphenol a affect decidualization of human endometrial stromal cells. Mol Cell Endocrinol. 2016 Feb 15;422:74-83. doi: 10.1016/j.mce.2015.11.017. Epub 2015 Nov 19.
• [9] Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect. 2015 Jan;123(1):80-7. doi: 10.1289/ehp.1408437. Epub 2014 Aug 19.
• [10] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [11] 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.
• [12] 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.