Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5N60RU)

• DOT Name: Myotrophin (MTPN)
• Synonyms: Protein V-1
• Gene Name: MTPN
• Related Disease:
  Breast cancer
  Breast carcinoma
  Essential hypertension
  Cardiac failure
  Congestive heart failure
  Dilated cardiomyopathy
  High blood pressure
  Non-insulin dependent diabetes
• UniProt ID: MTPN_HUMAN
• PDB ID: 3AAA; 7DF7; 7DSA; 7DSB
• Pfam ID: PF12796
• Sequence:
  MCDKEFMWALKNGDLDEVKDYVAKGEDVNRTLEGGRKPLHYAADCGQLEILEFLLLKGAD
  INAPDKHHITPLLSAVYEGHVSCVKLLLSKGADKTVKGPDGLTAFEATDNQAIKALLQ
• Function: Promotes dimerization of NF-kappa-B subunits and regulates NF-kappa-B transcription factor activity. Plays a role in the regulation of the growth of actin filaments. Inhibits the activity of the F-actin-capping protein complex formed by the CAPZA1 and CAPZB heterodimer. Promotes growth of cardiomyocytes, but not cardiomyocyte proliferation. Promotes cardiac muscle hypertrophy.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Essential hypertension	DIS7WI98	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Limited	Biomarker	[2]
Congestive heart failure	DIS32MEA	Limited	Biomarker	[2]
Dilated cardiomyopathy	DISX608J	Limited	Biomarker	[3]
High blood pressure	DISY2OHH	Limited	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Myotrophin (MTPN).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myotrophin (MTPN).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myotrophin (MTPN).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Myotrophin (MTPN).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Myotrophin (MTPN).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Myotrophin (MTPN).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myotrophin (MTPN).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Myotrophin (MTPN).	[13]

References

• [1] 9-cis Retinoic acid modulates myotrophin expression and its miR in physiological and pathophysiological cell models.Exp Cell Res. 2017 May 1;354(1):25-30. doi: 10.1016/j.yexcr.2017.03.022. Epub 2017 Mar 12.
• [2] The Human Myotrophin Variant Attenuates MicroRNA-Let-7 Binding Ability but Not Risk of Left Ventricular Hypertrophy in Human Essential Hypertension.PLoS One. 2015 Aug 14;10(8):e0135526. doi: 10.1371/journal.pone.0135526. eCollection 2015.
• [3] Characterization and functional significance of myotrophin: a gene with multiple transcripts.Gene. 2005 Jun 20;353(1):31-40. doi: 10.1016/j.gene.2005.03.045.
• [4] Myotrophin-kappaB DNA interaction in the initiation process of cardiac hypertrophy.Biochim Biophys Acta. 2002 May 8;1589(3):247-60. doi: 10.1016/s0167-4889(02)00178-7.
• [5] Over-expression of miR375 reduces glucose-induced insulin secretion in Nit-1 cells.Mol Biol Rep. 2011 Jun;38(5):3061-5. doi: 10.1007/s11033-010-9973-9. Epub 2010 Feb 3.
• [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] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [12] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.