Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMHUH1D)

DOT Name Lithostathine-1-alpha (REG1A)
Synonyms
Islet cells regeneration factor; ICRF; Islet of Langerhans regenerating protein; REG; Pancreatic stone protein; PSP; Pancreatic thread protein; PTP; Regenerating islet-derived protein 1-alpha; REG-1-alpha; Regenerating protein I alpha
Gene Name REG1A
Related Disease
Lung adenocarcinoma ( )
Adenocarcinoma ( )
Advanced cancer ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiovascular disease ( )
Chronic pancreatitis ( )
Colon cancer ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Corticobasal degeneration ( )
Epithelial ovarian cancer ( )
Familial spontaneous pneumothorax ( )
Frontotemporal dementia ( )
Gastric cancer ( )
Gastric neoplasm ( )
Glioma ( )
Hepatocellular carcinoma ( )
Hereditary diffuse gastric adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Noonan syndrome ( )
Parkinson disease ( )
Pick disease ( )
Progressive supranuclear palsy ( )
Promyelocytic leukaemia ( )
Rheumatoid arthritis ( )
Sjogren syndrome ( )
Stroke ( )
Type-1 diabetes ( )
Type-1/2 diabetes ( )
Carcinoma ( )
Myocardial infarction ( )
Acute myelogenous leukaemia ( )
Cardiac failure ( )
Congestive heart failure ( )
Non-insulin dependent diabetes ( )
Chronic kidney disease ( )
Crohn disease ( )
Inflammatory bowel disease ( )
Leukemia ( )
Matthew-Wood syndrome ( )
Melanoma ( )
Nasopharyngeal carcinoma ( )
Pancreatic cancer ( )
Psoriasis ( )
Tauopathy ( )
UniProt ID
REG1A_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1LIT; 1QDD
Pfam ID
PF00059
Sequence
MAQTSSYFMLISCLMFLSQSQGQEAQTELPQARISCPEGTNAYRSYCYYFNEDRETWVDA
DLYCQNMNSGNLVSVLTQAEGAFVASLIKESGTDDFNVWIGLHDPKKNRRWHWSSGSLVS
YKSWGIGAPSSVNPGYCVSLTSSTGFQKWKDVPCEDKFSFVCKFKN
Function Might act as an inhibitor of spontaneous calcium carbonate precipitation. May be associated with neuronal sprouting in brain, and with brain and pancreas regeneration.
Tissue Specificity
In pancreatic acinar cells and, in lower levels, in brain. Enhanced expression of PSP-related transcripts and intraneuronal accumulation of PSP-like proteins is found in brain from Alzheimer disease and Down syndrome patients.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung adenocarcinoma DISD51WR Definitive Altered Expression [1]
Adenocarcinoma DIS3IHTY Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Autoimmune disease DISORMTM Strong Biomarker [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Cardiovascular disease DIS2IQDX Strong Biomarker [6]
Chronic pancreatitis DISBUOMJ Strong Biomarker [7]
Colon cancer DISVC52G Strong Biomarker [5]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [8]
Colorectal neoplasm DISR1UCN Strong Biomarker [9]
Corticobasal degeneration DISSMOTT Strong Biomarker [10]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [11]
Familial spontaneous pneumothorax DISNM7SU Strong Biomarker [12]
Frontotemporal dementia DISKYHXL Strong Biomarker [13]
Gastric cancer DISXGOUK Strong Altered Expression [14]
Gastric neoplasm DISOKN4Y Strong Posttranslational Modification [15]
Glioma DIS5RPEH Strong Biomarker [16]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [17]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Strong Therapeutic [18]
Lung cancer DISCM4YA Strong Altered Expression [19]
Lung carcinoma DISTR26C Strong Biomarker [19]
Noonan syndrome DIS7Q7DN Strong Biomarker [20]
Parkinson disease DISQVHKL Strong Genetic Variation [21]
Pick disease DISP6X50 Strong Genetic Variation [22]
Progressive supranuclear palsy DISO5KRQ Strong Biomarker [23]
Promyelocytic leukaemia DISYGG13 Strong Altered Expression [24]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [25]
Sjogren syndrome DISUBX7H Strong Biomarker [26]
Stroke DISX6UHX Strong Biomarker [27]
Type-1 diabetes DIS7HLUB Strong Biomarker [28]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [29]
Carcinoma DISH9F1N moderate Biomarker [30]
Myocardial infarction DIS655KI moderate Biomarker [31]
Acute myelogenous leukaemia DISCSPTN Disputed Altered Expression [32]
Cardiac failure DISDC067 Disputed Genetic Variation [33]
Congestive heart failure DIS32MEA Disputed Genetic Variation [33]
Non-insulin dependent diabetes DISK1O5Z Disputed Genetic Variation [33]
Chronic kidney disease DISW82R7 Limited Biomarker [34]
Crohn disease DIS2C5Q8 Limited Biomarker [35]
Inflammatory bowel disease DISGN23E Limited Biomarker [36]
Leukemia DISNAKFL Limited Biomarker [37]
Matthew-Wood syndrome DISA7HR7 Limited Biomarker [38]
Melanoma DIS1RRCY Limited Altered Expression [39]
Nasopharyngeal carcinoma DISAOTQ0 Limited Genetic Variation [40]
Pancreatic cancer DISJC981 Limited Biomarker [41]
Psoriasis DIS59VMN Limited Biomarker [42]
Tauopathy DISY2IPA Limited Genetic Variation [22]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Lithostathine-1-alpha (REG1A). [43]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Lithostathine-1-alpha (REG1A). [45]
Octanal DMTN0OK Investigative Octanal increases the methylation of Lithostathine-1-alpha (REG1A). [46]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Coprexa DMA0WEK Phase 3 Coprexa increases the expression of Lithostathine-1-alpha (REG1A). [44]
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References

1 Inhibition of Shp2 suppresses mutant EGFR-induced lung tumors in transgenic mouse model of lung adenocarcinoma.Oncotarget. 2015 Mar 20;6(8):6191-202. doi: 10.18632/oncotarget.3356.
2 Dysregulation of Reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes.Cancer Biol Ther. 2006 Dec;5(12):1714-20. doi: 10.4161/cbt.5.12.3469. Epub 2006 Dec 30.
3 Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia.Clin Chem Lab Med. 2019 Mar 26;57(4):540-548. doi: 10.1515/cclm-2018-0154.
4 Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases.Front Immunol. 2019 Sep 24;10:2136. doi: 10.3389/fimmu.2019.02136. eCollection 2019.
5 Apoptosis of estrogen-receptor negative breast cancer and colon cancer cell lines by PTP alpha and src RNAi.Int J Cancer. 2008 May 1;122(9):1999-2007. doi: 10.1002/ijc.23321.
6 Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials.J Med Econ. 2019 Mar;22(3):280-287. doi: 10.1080/13696998.2018.1562817. Epub 2019 Jan 11.
7 Is genetic analysis helpful for diagnosing chronic pancreatitis in its early stage?.J Gastroenterol. 2007 Jan;42 Suppl 17:60-5. doi: 10.1007/s00535-006-1934-7.
8 A missense variant in PTPN12 associated with the risk of colorectal cancer by modifying Ras/MEK/ERK signaling.Cancer Epidemiol. 2019 Apr;59:109-114. doi: 10.1016/j.canep.2019.01.013. Epub 2019 Feb 4.
9 REG1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosis.Int J Cancer. 2008 Jul 15;123(2):409-413. doi: 10.1002/ijc.23466.
10 Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.PLoS One. 2017 Feb 16;12(2):e0172145. doi: 10.1371/journal.pone.0172145. eCollection 2017.
11 A water-soluble polysaccharide from the roots of Polygala tenuifolia suppresses ovarian tumor growth and angiogenesis in vivo.Int J Biol Macromol. 2018 Feb;107(Pt A):713-718. doi: 10.1016/j.ijbiomac.2017.09.043. Epub 2017 Sep 15.
12 A novel dual-covering method in video-assisted thoracic surgery for pediatric primary spontaneous pneumothorax.Surg Today. 2019 Jul;49(7):587-592. doi: 10.1007/s00595-019-01785-x. Epub 2019 Apr 6.
13 Cerebellar atrophy in neurodegeneration-a meta-analysis.J Neurol Neurosurg Psychiatry. 2017 Sep;88(9):780-788. doi: 10.1136/jnnp-2017-315607. Epub 2017 May 13.
14 DNA Methylation-Mediated Silencing of Regenerating Protein 1 Alpha (REG1A) Affects Gastric Cancer Prognosis.Med Sci Monit. 2017 Dec 9;23:5834-5843. doi: 10.12659/msm.904706.
15 REG Ialpha protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells.Carcinogenesis. 2008 Jan;29(1):76-83. doi: 10.1093/carcin/bgm250. Epub 2007 Nov 16.
16 Protein tyrosine phosphatase mu regulates glioblastoma cell growth and survival in vivo.Neuro Oncol. 2012 May;14(5):561-73. doi: 10.1093/neuonc/nos066. Epub 2012 Apr 14.
17 Hepatitis B virus X protein (HBx) enhances centrosomal P4.1-associated protein (CPAP) expression to promote hepatocarcinogenesis.J Biomed Sci. 2019 Jun 6;26(1):44. doi: 10.1186/s12929-019-0534-9.
18 Synergistic inhibitory effects of gastrin and histamine receptor antagonists on Helicobacter-induced gastric cancer.Gastroenterology. 2005 Jun;128(7):1965-83. doi: 10.1053/j.gastro.2005.03.027.
19 REG I gene expression is linked with the poor prognosis of lung adenocarcinoma and squamous cell carcinoma patients via discrete mechanisms.Oncol Rep. 2013 Dec;30(6):2625-31. doi: 10.3892/or.2013.2739. Epub 2013 Sep 19.
20 Identification of demethylincisterol A(3) as a selective inhibitor of protein tyrosine phosphatase Shp2.Eur J Pharmacol. 2017 Jan 15;795:124-133. doi: 10.1016/j.ejphar.2016.12.012. Epub 2016 Dec 8.
21 The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy.Mov Disord. 2019 Sep;34(9):1307-1314. doi: 10.1002/mds.27786. Epub 2019 Jul 12.
22 Involvement of Oligodendrocytes in Tau Seeding and Spreading in Tauopathies.Front Aging Neurosci. 2019 May 28;11:112. doi: 10.3389/fnagi.2019.00112. eCollection 2019.
23 Sensitivity and Specificity of Diagnostic Criteria for Progressive Supranuclear Palsy.Mov Disord. 2019 Aug;34(8):1144-1153. doi: 10.1002/mds.27619. Epub 2019 Feb 6.
24 E2f1 regulates the induction of promyelocytic leukemia zinc finger transcription in neuronal differentiation of pluripotent P19 embryonal carcinoma cells.Biochem Biophys Res Commun. 2019 May 7;512(3):629-634. doi: 10.1016/j.bbrc.2019.03.058. Epub 2019 Mar 23.
25 Abundant expression of the interleukin (IL)23 subunit p19, but low levels of bioactive IL23 in the rheumatoid synovium: differential expression and Toll-like receptor-(TLR) dependent regulation of the IL23 subunits, p19 and p40, in rheumatoid arthritis.Ann Rheum Dis. 2009 Jan;68(1):143-50. doi: 10.1136/ard.2007.082081. Epub 2008 Feb 14.
26 Novel Sjgren's autoantibodies found in fibromyalgia patients with sicca and/or xerostomia.Autoimmun Rev. 2019 Feb;18(2):199-202. doi: 10.1016/j.autrev.2018.09.004. Epub 2018 Dec 18.
27 Cost-effectiveness analysis of empagliflozin treatment in people with Type 2 diabetes and established cardiovascular disease in the EMPA-REG OUTCOME trial.Diabet Med. 2019 Nov;36(11):1494-1502. doi: 10.1111/dme.14076. Epub 2019 Jul 23.
28 Circulating Reg1 proteins and autoantibodies to Reg1 proteins as biomarkers of -cell regeneration and damage in type 1 diabetes.Horm Metab Res. 2010 Dec;42(13):955-60. doi: 10.1055/s-0030-1267206. Epub 2010 Oct 22.
29 Pancreatic stone protein/regenerating protein is a potential biomarker for endoplasmic reticulum stress in beta cells.Sci Rep. 2019 Mar 26;9(1):5199. doi: 10.1038/s41598-019-41604-4.
30 Expression of oxidized protein tyrosine phosphatase and H2AX predicts poor survival of gastric carcinoma patients.BMC Cancer. 2018 Aug 20;18(1):836. doi: 10.1186/s12885-018-4752-4.
31 The SGLT2 Inhibitor Empagliflozin Might Be a New Approach for the Prevention of Acute Kidney Injury.Kidney Blood Press Res. 2019;44(2):149-157. doi: 10.1159/000498963. Epub 2019 Apr 2.
32 NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells.Leukemia. 2016 Feb;30(2):473-83. doi: 10.1038/leu.2015.234. Epub 2015 Aug 26.
33 Eligibility of sodium-glucose co-transporter-2 inhibitors among patients with diabetes mellitus admitted for heart failure.ESC Heart Fail. 2020 Feb;7(1):274-278. doi: 10.1002/ehf2.12528. Epub 2019 Nov 20.
34 Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction.Curr Top Med Chem. 2019;19(20):1818-1849. doi: 10.2174/1568026619666190828161409.
35 IL-23 in inflammatory bowel diseases and colon cancer.Cytokine Growth Factor Rev. 2019 Feb;45:1-8. doi: 10.1016/j.cytogfr.2018.12.002. Epub 2018 Dec 12.
36 Expression of human REG family genes in inflammatory bowel disease and their molecular mechanism.Immunol Res. 2018 Dec;66(6):800-805. doi: 10.1007/s12026-019-9067-2.
37 Targeting protein tyrosine phosphatase SHP2 for the treatment of PTPN11-associated malignancies.Mol Cancer Ther. 2013 Sep;12(9):1738-48. doi: 10.1158/1535-7163.MCT-13-0049-T. Epub 2013 Jul 3.
38 Nano-biotinylated liposome-based immunoassay for the ultrasensitive detection of protein biomarker in urine.Talanta. 2018 Mar 1;179:472-477. doi: 10.1016/j.talanta.2017.11.031. Epub 2017 Nov 21.
39 Epigenetic regulation of REG1A and chemosensitivity of cutaneous melanoma.Epigenetics. 2013 Oct;8(10):1043-52. doi: 10.4161/epi.25810. Epub 2013 Jul 31.
40 Association of regenerating gene 1A single-nucleotide polymorphisms and nasopharyngeal carcinoma susceptibility in southern Chinese population.Eur Arch Otorhinolaryngol. 2020 Jan;277(1):221-226. doi: 10.1007/s00405-019-05645-9. Epub 2019 Sep 20.
41 A novel plectin/integrin-targeted bispecific molecular probe for magnetic resonance/near-infrared imaging of pancreatic cancer.Biomaterials. 2018 Nov;183:173-184. doi: 10.1016/j.biomaterials.2018.08.048. Epub 2018 Aug 26.
42 Tildrakizumab: A Review in Moderate-to-Severe Plaque Psoriasis.Am J Clin Dermatol. 2019 Apr;20(2):295-306. doi: 10.1007/s40257-019-00435-9.
43 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.
44 Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
45 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
46 DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.