Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT303R2T)

• DOT Name: Mitochondrial inner membrane protease ATP23 homolog (ATP23)
• Synonyms: EC 3.4.24.-; Ku70-binding protein 3; XRCC6-binding protein 1
• Gene Name: ATP23
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Anaplastic astrocytoma
  Astrocytoma
  Glioma
  Malignant soft tissue neoplasm
  Sarcoma
• UniProt ID: ATP23_HUMAN
• EC Number: 3.4.24.-
• Pfam ID: PF09768
• Sequence:
  MAGAPDERRRGPAAGEQLQQQHVSCQVFPERLAQGNPQQGFFSSFFTSNQKCQLRLLKTL
  ETNPYVKLLLDAMKHSGCAVNKDRHFSCEDCNGNVSGGFDASTSQIVLCQNNIHNQAHMN
  RVVTHELIHAFDHCRAHVDWFTNIRHLACSEVRAANLSGDCSLVNEIFRLHFGLKQHHQT
  CVRDRATLSILAVRNISKEVAKKAVDEVFESCFNDHEPFGRIPHNKTYARYAHRDFENRD
  RYYSNI

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[1]
Anaplastic astrocytoma	DISSBE0K	Strong	Biomarker	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Biomarker	[3]
Sarcoma	DISZDG3U	Limited	Biomarker	[3]

16 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 Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitochondrial inner membrane protease ATP23 homolog (ATP23).	[9]

References

• [1] Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation.Int J Oncol. 2013 Jul;43(1):50-6. doi: 10.3892/ijo.2013.1937. Epub 2013 May 13.
• [2] KUB3 amplification and overexpression in human gliomas.Glia. 2001 Oct;36(1):1-10. doi: 10.1002/glia.1090.
• [3] Pol deficiency induces moderate shortening of P53(-/-) mouse lifespan and modifies tumor spectrum.DNA Repair (Amst). 2017 Jun;54:40-45. doi: 10.1016/j.dnarep.2017.04.001. Epub 2017 Apr 10.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [10] 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.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] 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.
• [13] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [14] 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.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] 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.