Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT805SMH)

• DOT Name: Ribose-5-phosphate isomerase (RPIA)
• Synonyms: EC 5.3.1.6; Phosphoriboisomerase
• Gene Name: RPIA
• Related Disease:
  Chagas disease
  Colon cancer
  Colon carcinoma
  Familial adenomatous polyposis
  Medullary thyroid gland carcinoma
  Metabolic disorder
  Peripheral neuropathy
  Plasma cell myeloma
  Ribose-5-P isomerase deficiency
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Thyroid gland papillary carcinoma
  Thyroid tumor
• UniProt ID: RPIA_HUMAN
• EC Number: 5.3.1.6
• Pfam ID: PF06026
• Sequence:
  MQRPGPFSTLYGRVLAPLPGRAGGAASGGGGNSWDLPGSHVRLPGRAQSGTRGGAGNTST
  SCGDSNSICPAPSTMSKAEEAKKLAGRAAVENHVRNNQVLGIGSGSTIVHAVQRIAERVK
  QENLNLVCIPTSFQARQLILQYGLTLSDLDRHPEIDLAIDGADEVDADLNLIKGGGGCLT
  QEKIVAGYASRFIVIADFRKDSKNLGDQWHKGIPIEVIPMAYVPVSRAVSQKFGGVVELR
  MAVNKAGPVVTDNGNFILDWKFDRVHKWSEVNTAIKMIPGVVDTGLFINMAERVYFGMQD
  GSVNMREKPFC
• Function: Catalyzes the reversible conversion of ribose-5-phosphate to ribulose 5-phosphate and participates in the first step of the non-oxidative branch of the pentose phosphate pathway.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  RPIA deficiency (R-HSA-6791461)
  Pentose phosphate pathway (R-HSA-71336)
  RPIA deficiency (R-HSA-5659996)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chagas disease	DIS8KNVF	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[2]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Biomarker	[3]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[4]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[4]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[5]
Ribose-5-P isomerase deficiency	DISOIVXL	Strong	Autosomal recessive	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[6]
Liver cancer	DISDE4BI	moderate	Altered Expression	[6]
Neoplasm	DISZKGEW	Limited	Altered Expression	[7]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[8]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ribose-5-phosphate isomerase (RPIA).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribose-5-phosphate isomerase (RPIA).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribose-5-phosphate isomerase (RPIA).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ribose-5-phosphate isomerase (RPIA).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ribose-5-phosphate isomerase (RPIA).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Ribose-5-phosphate isomerase (RPIA).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ribose-5-phosphate isomerase (RPIA).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ribose-5-phosphate isomerase (RPIA).	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Ribose-5-phosphate isomerase (RPIA).	[16]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Ribose-5-phosphate isomerase (RPIA).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ribose-5-phosphate isomerase (RPIA).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ribose-5-phosphate isomerase (RPIA).	[19]

References

• [1] In silico identification of inhibitors of ribose 5-phosphate isomerase from Trypanosoma cruzi using ligand and structure based approaches.J Mol Graph Model. 2017 Oct;77:168-180. doi: 10.1016/j.jmgm.2017.08.007. Epub 2017 Aug 12.
• [2] Identification of a noncanonical function for ribose-5-phosphate isomerase A promotes colorectal cancer formation by stabilizing and activating -catenin via a novel C-terminal domain.PLoS Biol. 2018 Jan 16;16(1):e2003714. doi: 10.1371/journal.pbio.2003714. eCollection 2018 Jan.
• [3] Apoptotic cell death induction and angiogenesis inhibition in large established medullary thyroid carcinoma xenografts by Ret inhibitor RPI-1.Biochem Pharmacol. 2006 Aug 14;72(4):405-14. doi: 10.1016/j.bcp.2006.05.002. Epub 2006 Jun 6.
• [4] Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. Am J Hum Genet. 2004 Apr;74(4):745-51. doi: 10.1086/383204. Epub 2004 Feb 25.
• [5] Concomitant downregulation of proliferation/survival pathways dependent on FGF-R3, JAK2 and BCMA in human multiple myeloma cells by multi-kinase targeting.Biochem Pharmacol. 2009 Nov 1;78(9):1139-47. doi: 10.1016/j.bcp.2009.06.023. Epub 2009 Jun 23.
• [6] Ribose-5-phosphate isomerase A overexpression promotes liver cancer development in transgenic zebrafish via activation of ERK and -catenin pathways.Carcinogenesis. 2019 May 14;40(3):461-473. doi: 10.1093/carcin/bgy155.
• [7] Ribose-5-phosphate isomerase A regulates hepatocarcinogenesis via PP2A and ERK signaling.Int J Cancer. 2015 Jul 1;137(1):104-15. doi: 10.1002/ijc.29361. Epub 2014 Dec 12.
• [8] Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1.Cell Mol Life Sci. 2003 Jul;60(7):1449-59. doi: 10.1007/s00018-003-2381-8.
• [9] 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.
• [10] 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.
• [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] 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.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [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] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [17] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.