Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY5QDBN)

• DOT Name: Mesoderm posterior protein 1 (MESP1)
• Synonyms: Class C basic helix-loop-helix protein 5; bHLHc5
• Gene Name: MESP1
• Related Disease:
  Advanced cancer
  Immunodeficiency
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Ventricular septal defect
  Congenital heart disease
• UniProt ID: MESP1_HUMAN
• Pfam ID: PF00010
• Sequence:
  MAQPLCPPLSESWMLSAAWGPTRRPPPSDKDCGRSLVSSPDSWGSTPADSPVASPARPGT
  LRDPRAPSVGRRGARSSRLGSGQRQSASEREKLRMRTLARALHELRRFLPPSVAPAGQSL
  TKIETLRLAIRYIGHLSAVLGLSEESLQRRCRQRGDAGSPRGCPLCPDDCPAQMQTRTQA
  EGQGQGRGLGLVSAVRAGASWGSPPACPGARAAPEPRDPPALFAEAACPEGQAMEPSPPS
  PLLPGDVLALLETWMPLSPLEWLPEEPK
• Function: Transcription factor. Plays a role in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm. Defines the rostrocaudal patterning of the somites by participating in distinct Notch pathways.
• Reactome Pathway: Cardiogenesis (R-HSA-9733709)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Immunodeficiency	DIS093I0	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]
Ventricular septal defect	DISICO41	Strong	Genetic Variation	[3]
Congenital heart disease	DISQBA23	Limited	Biomarker	[4]

2 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 Mesoderm posterior protein 1 (MESP1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Mesoderm posterior protein 1 (MESP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mesoderm posterior protein 1 (MESP1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mesoderm posterior protein 1 (MESP1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Mesoderm posterior protein 1 (MESP1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mesoderm posterior protein 1 (MESP1).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Mesoderm posterior protein 1 (MESP1).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Mesoderm posterior protein 1 (MESP1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mesoderm posterior protein 1 (MESP1).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Mesoderm posterior protein 1 (MESP1).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Mesoderm posterior protein 1 (MESP1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mesoderm posterior protein 1 (MESP1).	[16]

References

• [1] Aberrant expression of embryonic mesendoderm factor MESP1 promotes tumorigenesis.EBioMedicine. 2019 Dec;50:55-66. doi: 10.1016/j.ebiom.2019.11.012. Epub 2019 Nov 21.
• [2] MicroRNA-21 coordinates human multipotent cardiovascular progenitors therapeutic potential.Stem Cells. 2014 Nov;32(11):2908-22. doi: 10.1002/stem.1789.
• [3] MESP1 lossoffunction mutation contributes to double outlet right ventricle.Mol Med Rep. 2017 Sep;16(3):2747-2754. doi: 10.3892/mmr.2017.6875. Epub 2017 Jun 29.
• [4] Mutational analysis of the human MESP1 gene in patients with congenital heart disease reveals a highly variable sequence in exon 1.Eur J Med Genet. 2013 Nov;56(11):591-8. doi: 10.1016/j.ejmg.2013.09.001. Epub 2013 Sep 19.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 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 Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [16] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.