Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQUA3TG)

• DOT Name: PX domain-containing protein 1 (PXDC1)
• Gene Name: PXDC1
• UniProt ID: PXDC1_HUMAN
• Sequence:
  MASAVFEGTSLVNMFVRGCWVNGIRRLIVSRRGDEEEFFEIRTEWSDRSVLYLHRSLADL
  GRLWQRLRDAFPEDRSELAQGPLRQGLVAIKEAHDIETRLNEVEKLLKTIISMPCKYSRS
  EVVLTFFERSPLDQVLKNDNVHKIQPSFQSPVKISEIMRSNGFCLANTETIVIDHSIPNG
  RDQQLGVDPTEHLFENGSEFPSELEDGDDPAAYVTNLSYYHLVPFETDIWD

Molecular Interaction Atlas (MIA) of This DOT

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 PX domain-containing protein 1 (PXDC1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PX domain-containing protein 1 (PXDC1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of PX domain-containing protein 1 (PXDC1).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of PX domain-containing protein 1 (PXDC1).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of PX domain-containing protein 1 (PXDC1).	[5]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of PX domain-containing protein 1 (PXDC1).	[6]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of PX domain-containing protein 1 (PXDC1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PX domain-containing protein 1 (PXDC1).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of PX domain-containing protein 1 (PXDC1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of PX domain-containing protein 1 (PXDC1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of PX domain-containing protein 1 (PXDC1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PX domain-containing protein 1 (PXDC1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of PX domain-containing protein 1 (PXDC1).	[12]

References

• [1] 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.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [5] 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.
• [6] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [7] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.