Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKC8T3E)

• DOT Name: Protein PIMREG (PIMREG)
• Synonyms: CALM-interactor expressed in thymus and spleen; PICALM-interacting mitotic regulator; Regulator of chromosome segregation protein 1
• Gene Name: PIMREG
• Related Disease:
  Adult lymphoma
  Lymphoma
  Pediatric lymphoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colitis
  Coronary atherosclerosis
  Neoplasm
  Nervous system inflammation
  Triple negative breast cancer
  Pancreatic cancer
• UniProt ID: PIMRE_HUMAN
• Pfam ID: PF07326
• Sequence:
  MASRWQNMGTSVRRRSLQHQEQLEDSKELQPVVSHQETSVGALGSLCRQFQRRLPLRAVN
  LNLRAGPSWKRLETPEPGQQGLQAAARSAKSALGAVSQRIQESCQSGTKWLVETQVKARR
  RKRGAQKGSGSPTHSLSQKSTRLSGAAPAHSAADPWEKEHHRLSVRMGSHAHPLRRSRRE
  AAFRSPYSSTEPLCSPSESDSDLEPVGAGIQHLQKLSQELDEAIMAEERKQALSDRQGFI
  LKDVYASP
• Function: During mitosis, may play a role in the control of metaphase-to-anaphase transition.
• Tissue Specificity: Expressed in thymus (at protein level). Detected in spleen, colon, ovary and small intestines.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Definitive	Altered Expression	[1]
Lymphoma	DISN6V4S	Definitive	Altered Expression	[1]
Pediatric lymphoma	DIS51BK2	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[2]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[5]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[6]

3 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 Protein PIMREG (PIMREG).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein PIMREG (PIMREG).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Protein PIMREG (PIMREG).	[21]

17 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 Protein PIMREG (PIMREG).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein PIMREG (PIMREG).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein PIMREG (PIMREG).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein PIMREG (PIMREG).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein PIMREG (PIMREG).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein PIMREG (PIMREG).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein PIMREG (PIMREG).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein PIMREG (PIMREG).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein PIMREG (PIMREG).	[15]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Protein PIMREG (PIMREG).	[16]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Protein PIMREG (PIMREG).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein PIMREG (PIMREG).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein PIMREG (PIMREG).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein PIMREG (PIMREG).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Protein PIMREG (PIMREG).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein PIMREG (PIMREG).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein PIMREG (PIMREG).	[11]

References

• [1] The CALM and CALM/AF10 interactor CATS is a marker for proliferation.Mol Oncol. 2008 Dec;2(4):356-67. doi: 10.1016/j.molonc.2008.08.001. Epub 2008 Sep 4.
• [2] FAM64A positively regulates STAT3 activity to promote Th17 differentiation and colitis-associated carcinogenesis.Proc Natl Acad Sci U S A. 2019 May 21;116(21):10447-10452. doi: 10.1073/pnas.1814336116. Epub 2019 May 6.
• [3] Up-regulation of FAM64A promotes epithelial-to-mesenchymal transition and enhances stemness features in breast cancer cells.Biochem Biophys Res Commun. 2019 May 28;513(2):472-478. doi: 10.1016/j.bbrc.2019.03.207. Epub 2019 Apr 9.
• [4] Increased plasma levels of CATS mRNA but not CATB mRNA in patients with coronary atherosclerosis.Clin Biochem. 2010 Dec;43(18):1427-30. doi: 10.1016/j.clinbiochem.2010.09.017. Epub 2010 Sep 27.
• [5] Integrated analysis of expression profiling data identifies three genes in correlation with poor prognosis of triple-negative breast cancer.Int J Oncol. 2014 Jun;44(6):2025-33. doi: 10.3892/ijo.2014.2352. Epub 2014 Mar 20.
• [6] Aberrant FAM64A mRNA expression is an independent predictor of poor survival in pancreatic cancer.PLoS One. 2019 Jan 29;14(1):e0211291. doi: 10.1371/journal.pone.0211291. eCollection 2019.
• [7] 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.
• [8] 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.
• [9] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] 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.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [17] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [18] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] 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.
• [21] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [22] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [23] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.