Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB1AWPM)

• DOT Name: Peroxisomal membrane protein 11B (PEX11B)
• Synonyms: Peroxin-11B; Peroxisomal biogenesis factor 11B; Protein PEX11 homolog beta; PEX11-beta
• Gene Name: PEX11B
• Related Disease:
  Peroxisome biogenesis disorder
  Peroxisome biogenesis disorder 14B
  Zellweger spectrum disorders
  Intellectual disability
• UniProt ID: PX11B_HUMAN
• Pfam ID: PF05648
• Sequence:
  MDAWVRFSAQSQARERLCRAAQYACSLLGHALQRHGASPELQKQIRQLESHLSLGRKLLR
  LGNSADALESAKRAVHLSDVVLRFCITVSHLNRALYFACDNVLWAGKSGLAPRVDQEKWA
  QRSFRYYLFSLIMNLSRDAYEIRLLMEQESSACSRRLKGSGGGVPGGSETGGLGGPGTPG
  GGLPQLALKLRLQVLLLARVLRGHPPLLLDVVRNACDLFIPLDKLGLWRCGPGIVGLCGL
  VSSILSILTLIYPWLRLKP
• Function: Involved in peroxisomal proliferation. May regulate peroxisome division by recruiting the dynamin-related GTPase DNM1L to the peroxisomal membrane. Promotes membrane protrusion and elongation on the peroxisomal surface.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway: Class I peroxisomal membrane protein import (R-HSA-9603798)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peroxisome biogenesis disorder	DISBQ6QJ	Definitive	Autosomal recessive	[1]
Peroxisome biogenesis disorder 14B	DISQNNXB	Definitive	Autosomal recessive	[2]
Zellweger spectrum disorders	DISW52CE	Supportive	Autosomal recessive	[2]
Intellectual disability	DISMBNXP	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Peroxisomal membrane protein 11B (PEX11B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Peroxisomal membrane protein 11B (PEX11B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Peroxisomal membrane protein 11B (PEX11B).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peroxisomal membrane protein 11B (PEX11B).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Peroxisomal membrane protein 11B (PEX11B).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Peroxisomal membrane protein 11B (PEX11B).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Peroxisomal membrane protein 11B (PEX11B).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Peroxisomal membrane protein 11B (PEX11B).	[11]

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] A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11 gene. J Med Genet. 2012 May;49(5):307-13. doi: 10.1136/jmedgenet-2012-100778.
• [3] Novel PEX11B Mutations Extend the Peroxisome Biogenesis Disorder 14B Phenotypic Spectrum and Underscore Congenital Cataract as an Early Feature.Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):594-603. doi: 10.1167/iovs.16-21026.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.