Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9837QM)

• DOT Name: Prefoldin subunit 1 (PFDN1)
• Gene Name: PFDN1
• Related Disease:
  Colorectal carcinoma
  Neoplasm
  Nasopharyngeal carcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
• UniProt ID: PFD1_HUMAN
• PDB ID: 6NR8; 6NR9; 6NRB; 6NRC; 6NRD; 7WU7
• Pfam ID: PF01920
• Sequence:
  MAAPVDLELKKAFTELQAKVIDTQQKVKLADIQIEQLNRTKKHAHLTDTEIMTLVDETNM
  YEGVGRMFILQSKEAIHSQLLEKQKIAEEKIKELEQKKSYLERSVKEAEDNIREMLMARR
  AQ
• Function: Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.
• Reactome Pathway: Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[2]
Lung cancer	DISCM4YA	Limited	Biomarker	[3]
Lung carcinoma	DISTR26C	Limited	Biomarker	[3]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Prefoldin subunit 1 (PFDN1) affects the response to substance of Acetaminophen.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prefoldin subunit 1 (PFDN1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Prefoldin subunit 1 (PFDN1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Prefoldin subunit 1 (PFDN1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Prefoldin subunit 1 (PFDN1).	[7]

References

• [1] PFDN1, an indicator for colorectal cancer prognosis, enhances tumor cell proliferation and motility through cytoskeletal reorganization.Med Oncol. 2015 Dec;32(12):264. doi: 10.1007/s12032-015-0710-z. Epub 2015 Nov 9.
• [2] Selection of reliable reference genes for gene expression study in nasopharyngeal carcinoma.Acta Pharmacol Sin. 2010 Nov;31(11):1487-94. doi: 10.1038/aps.2010.115.
• [3] Prefoldin 1 promotes EMT and lung cancer progression by suppressing cyclin A expression.Oncogene. 2017 Feb 16;36(7):885-898. doi: 10.1038/onc.2016.257. Epub 2016 Oct 3.
• [4] 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.
• [5] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [6] 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.
• [7] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [8] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.