Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYYV8LN)

• DOT Name: TMF-regulated nuclear protein 1 (TRNP1)
• Gene Name: TRNP1
• UniProt ID: TRNP1_HUMAN
• Sequence:
  MPGCRISACGPGAQEGTAEQRSPPPPWDPMPSSQPPPPTPTLTPTPTPGQSPPLPDAAGA
  SAGAAEDQELQRWRQGASGIAGLAGPGGGSGAAAGAGGRALELAEARRRLLEVEGRRRLV
  SELESRVLQLHRVFLAAELRLAHRAESLSRLSGGVAQAELYLAAHGSRLKKGPRRGRRGR
  PPALLASALGLGGCVPWGAGRLRRGHGPEPDSPFRRSPPRGPASPQR
• Function: DNA-binding factor that regulates the expression of a subset of genes and plays a key role in tangential, radial, and lateral expansion of the brain neocortex. Regulates neural stem cells proliferation and the production of intermediate neural progenitors and basal radial glial cells affecting the process of cerebral cortex gyrification. May control the proliferation rate of cells by regulating their progression through key cell-cycle transition points.

Molecular Interaction Atlas (MIA) of This DOT

15 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 TMF-regulated nuclear protein 1 (TRNP1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of TMF-regulated nuclear protein 1 (TRNP1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of TMF-regulated nuclear protein 1 (TRNP1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[6]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of TMF-regulated nuclear protein 1 (TRNP1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of TMF-regulated nuclear protein 1 (TRNP1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of TMF-regulated nuclear protein 1 (TRNP1).	[13]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] 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.
• [7] 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.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [10] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] 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.