Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY5Q42N)

• DOT Name: Peptidyl-prolyl cis-trans isomerase C (PPIC)
• Synonyms: PPIase C; EC 5.2.1.8; Cyclophilin C; Rotamase C
• Gene Name: PPIC
• Related Disease:
  Alzheimer disease
  Coronary atherosclerosis
  Coronary heart disease
  Neoplasm
  Chronic obstructive pulmonary disease
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
• UniProt ID: PPIC_HUMAN
• PDB ID: 2ESL
• EC Number: 5.2.1.8
• Pfam ID: PF00160
• Sequence:
  MGPGPRLLLPLVLCVGLGALVFSSGAEGFRKRGPSVTAKVFFDVRIGDKDVGRIVIGLFG
  KVVPKTVENFVALATGEKGYGYKGSKFHRVIKDFMIQGGDITTGDGTGGVSIYGETFPDE
  NFKLKHYGIGWVSMANAGPDTNGSQFFITLTKPTWLDGKHVVFGKVIDGMTVVHSIELQA
  TDGHDRPLTNCSIINSGKIDVKTPFVVEIADW
• Function: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.
• Tissue Specificity: Expressed in kidney, skeletal muscle, pancreas, heart, lung, liver and to a lower extent in brain.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[2]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[4]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[4]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[4]

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 Peptidyl-prolyl cis-trans isomerase C (PPIC).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[19]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[17]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peptidyl-prolyl cis-trans isomerase C (PPIC).	[21]

References

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• [8] 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.
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• [10] 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.
• [11] 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.
• [12] 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.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [17] 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.
• [18] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [19] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [20] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [21] 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.