Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPGO23E)

• DOT Name: Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1)
• Synonyms: EC 1.8.1.-
• Gene Name: PYROXD1
• Related Disease:
  Myofibrillar myopathy 8
  Myopathy
  Colon cancer
  Colon carcinoma
  Limb-girdle muscular dystrophy
  Myofibrillar myopathy
• UniProt ID: PYRD1_HUMAN
• PDB ID: 6ZK7
• EC Number: 1.8.1.-
• Pfam ID: PF07992 ; PF18267
• Sequence:
  MEAARPPPTAGKFVVVGGGIAGVTCAEQLATHFPSEDILLVTASPVIKAVTNFKQISKIL
  EEFDVEEQSSTMLGKRFPNIKVIESGVKQLKSEEHCIVTEDGNQHVYKKLCLCAGAKPKL
  ICEGNPYVLGIRDTDSAQEFQKQLTKAKRIMIIGNGGIALELVYEIEGCEVIWAIKDKAI
  GNTFFDAGAAEFLTSKLIAEKSEAKIAHKRTRYTTEGRKKEARSKSKADNVGSALGPDWH
  EGLNLKGTKEFSHKIHLETMCEVKKIYLQDEFRILKKKSFTFPRDHKSVTADTEMWPVYV
  ELTNEKIYGCDFIVSATGVTPNVEPFLHGNSFDLGEDGGLKVDDHMHTSLPDIYAAGDIC
  TTSWQLSPVWQQMRLWTQARQMGWYAAKCMAAASSGDSIDMDFSFELFAHVTKFFNYKVV
  LLGKYNAQGLGSDHELMLRCTKGREYIKVVMQNGRMMGAVLIGETDLEETFENLILNQMN
  LSSYGEDLLDPNIDIEDYFD
• Function: Probable FAD-dependent oxidoreductase; involved in the cellular oxidative stress response. Required for normal sarcomere structure and muscle fiber integrity.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myofibrillar myopathy 8	DIS57485	Definitive	Autosomal recessive	[1]
Myopathy	DISOWG27	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Limited	Biomarker	[3]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[3]
Limb-girdle muscular dystrophy	DISI9Y1Z	Limited	Genetic Variation	[4]
Myofibrillar myopathy	DISF24LW	Limited	Genetic Variation	[4]

2 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 Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[12]

9 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 Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXD1).	[14]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Clinical, histological, and genetic characterization of PYROXD1-related myopathy.Acta Neuropathol Commun. 2019 Aug 27;7(1):138. doi: 10.1186/s40478-019-0781-8.
• [3] A siRNA-based method for efficient silencing of PYROXD1 gene expression in the colon cancer cell line HCT116.J Cell Biochem. 2019 Dec;120(12):19310-19317. doi: 10.1002/jcb.26858. Epub 2019 Sep 10.
• [4] Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy.J Neurol. 2019 Feb;266(2):353-360. doi: 10.1007/s00415-018-9137-8. Epub 2018 Dec 4.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.