Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYMYR85)

• DOT Name: Galectin-10 (CLC)
• Synonyms: Gal-10; Charcot-Leyden crystal protein; CLC; Eosinophil lysophospholipase; Lysolecithin acylhydrolase
• Gene Name: CLC
• Related Disease:
  Allergic rhinitis
  Alzheimer disease
  Bartter syndrome
  Blindness
  Coeliac disease
  Dent disease
  Epilepsy
  Familial adenomatous polyposis
  Glioma
  Nasal polyp
  Osteoarthritis
  Osteopetrosis
  Osteoporosis
  Psoriasis
  Advanced cancer
  Asthma
  Craniosynostosis
  High blood pressure
  Keratoconus
  Nephropathy
  Acute myelogenous leukaemia
  Bronchiolitis
  Colorectal carcinoma
  Eosinophilic esophagitis
  Immune system disorder
  Male infertility
  Myasthenia gravis
  Myotonia congenita, autosomal dominant
  Nasopharyngeal carcinoma
  Thyroid gland undifferentiated (anaplastic) carcinoma
• UniProt ID: LEG10_HUMAN
• PDB ID: 1G86 ; 1HDK ; 1LCL ; 1QKQ ; 5XRG ; 5XRH ; 5XRI ; 5XRJ ; 5XRK ; 5XRL ; 5XRM ; 5XRN ; 5XRO ; 5XRP ; 5YT4 ; 6A1S ; 6A1T ; 6A1U ; 6A1V ; 6A1X ; 6A1Y ; 6GKQ ; 6GKS ; 6GKT ; 6GKU ; 6GLW ; 6GLX ; 6L64 ; 6L67 ; 6L68 ; 6L6A ; 6L6B ; 6L6C ; 6L6D ; 6QRN
• Pfam ID: PF00337
• Sequence:
  MSLLPVPYTEAASLSTGSTVTIKGRPLACFLNEPYLQVDFHTEMKEESDIVFHFQVCFGR
  RVVMNSREYGAWKQQVESKNMPFQDGQEFELSISVLPDKYQVMVNGQSSYTFDHRIKPEA
  VKMVQVWRDISLTKFNVSYLKR
• Function: Regulates immune responses through the recognition of cell-surface glycans. Essential for the anergy and suppressive function of CD25-positive regulatory T-cells (Treg).
• Tissue Specificity: Expressed abundantly in the bone marrow. Expressed exclusively by eosinophils and basophils. Not detected in monocytes and neutrophils. Expressed in CD25-positive regulatory T-cells (Treg) (at protein level). Found in intestinal tissue from patients with Celiac disease, expression is directly related to the histological grade of mucosal damage and to the number of eosinophils found in the duodenal lesion (at protein level). Found in sputum of patients with eosinophilic inflammatory diseases such as asthma (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Bartter syndrome	DIS7D44B	Strong	Genetic Variation	[3]
Blindness	DISTIM10	Strong	Biomarker	[3]
Coeliac disease	DISIY60C	Strong	Biomarker	[4]
Dent disease	DISRDLFN	Strong	Genetic Variation	[3]
Epilepsy	DISBB28L	Strong	Genetic Variation	[3]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[6]
Nasal polyp	DISLP3XE	Strong	Biomarker	[7]
Osteoarthritis	DIS05URM	Strong	Biomarker	[8]
Osteopetrosis	DIS7GHNM	Strong	Genetic Variation	[3]
Osteoporosis	DISF2JE0	Strong	Biomarker	[9]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[10]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[11]
Asthma	DISW9QNS	moderate	Biomarker	[12]
Craniosynostosis	DIS6J405	moderate	Biomarker	[13]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[14]
Keratoconus	DISOONXH	moderate	Altered Expression	[15]
Nephropathy	DISXWP4P	Disputed	Altered Expression	[16]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[17]
Bronchiolitis	DISEE9BG	Limited	Altered Expression	[18]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[19]
Eosinophilic esophagitis	DISR8WSB	Limited	Altered Expression	[20]
Immune system disorder	DISAEGPH	Limited	Altered Expression	[21]
Male infertility	DISY3YZZ	Limited	Genetic Variation	[22]
Myasthenia gravis	DISELRCI	Limited	Altered Expression	[23]
Myotonia congenita, autosomal dominant	DISAC9U9	Limited	Genetic Variation	[24]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[25]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Galectin-10 (CLC) affects the response to substance of Aspirin.	[32]

4 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 Galectin-10 (CLC).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Galectin-10 (CLC).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Galectin-10 (CLC).	[28]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Galectin-10 (CLC).	[29]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Galectin-10 (CLC).	[30]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Galectin-10 (CLC).	[31]

References

• [1] Identification of pathogenic genes and upstream regulators in allergic rhinitis.Int J Pediatr Otorhinolaryngol. 2018 Dec;115:97-103. doi: 10.1016/j.ijporl.2018.09.005. Epub 2018 Sep 19.
• [2] A Curcumin Analog Reduces Levels of the Alzheimer's Disease-Associated Amyloid- Protein by Modulating APP Processing and Autophagy.J Alzheimers Dis. 2019;72(3):761-771. doi: 10.3233/JAD-190562.
• [3] Physiological functions of CLC Cl- channels gleaned from human genetic disease and mouse models.Annu Rev Physiol. 2005;67:779-807. doi: 10.1146/annurev.physiol.67.032003.153245.
• [4] Galectin-10, eosinophils, and celiac disease.Ann N Y Acad Sci. 2009 Sep;1173:357-64. doi: 10.1111/j.1749-6632.2009.04627.x.
• [5] Transcriptional changes between uninflamed ulcerative colitis and familial adenomatous polyposis pouch mucosa can be attributed to an altered immune response.Acta Biochim Pol. 2015;62(1):69-75. doi: 10.18388/abp.2014_778. Epub 2015 Feb 4.
• [6] Role of Cl(-) channels in primary brain tumour.Cell Calcium. 2019 Jul;81:1-11. doi: 10.1016/j.ceca.2019.05.004. Epub 2019 May 14.
• [7] Superior turbinate eosinophilia correlates with olfactory deficit in chronic rhinosinusitis patients.Laryngoscope. 2017 Oct;127(10):2210-2218. doi: 10.1002/lary.26555. Epub 2017 Mar 21.
• [8] Cytokine receptor-like factor 1 is highly expressed in damaged human knee osteoarthritic cartilage and involved in osteoarthritis downstream of TGF-beta.Calcif Tissue Int. 2010 Jan;86(1):47-57. doi: 10.1007/s00223-009-9311-1. Epub 2009 Nov 17.
• [9] Straightening out the renal tubule: advances in the molecular basis of the inherited tubulopathies.QJM. 1998 Jan;91(1):5-12. doi: 10.1093/qjmed/91.1.5.
• [10] Role of nitric oxide-scavenging activity of Karanjin and Pongapin in the treatment of Psoriasis.3 Biotech. 2018 Aug;8(8):338. doi: 10.1007/s13205-018-1337-5. Epub 2018 Jul 25.
• [11] NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma.Oncotarget. 2017 Jun 27;8(26):42613-42620. doi: 10.18632/oncotarget.17300.
• [12] A sputum 6-gene signature predicts future exacerbations of poorly controlled asthma.J Allergy Clin Immunol. 2019 Jul;144(1):51-60.e11. doi: 10.1016/j.jaci.2018.12.1020. Epub 2019 Jan 22.
• [13] Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2812-2820.e3. doi: 10.1016/j.jaip.2019.05.009. Epub 2019 May 22.
• [14] Kidney CLC-K chloride channels inhibitors: structure-based studies and efficacy in hypertension and associated CLC-K polymorphisms.J Hypertens. 2016 May;34(5):981-92. doi: 10.1097/HJH.0000000000000876.
• [15] Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients.Cornea. 2005 Aug;24(6):661-8. doi: 10.1097/01.ico.0000153556.59407.69.
• [16] In vivo role of CLC chloride channels in the kidney.Am J Physiol Renal Physiol. 2000 Nov;279(5):F802-8. doi: 10.1152/ajprenal.2000.279.5.F802.
• [17] Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis.Haematologica. 2002 Jun;87(6):569-77.
• [18] Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis.BMC Infect Dis. 2006 Dec 13;6:175. doi: 10.1186/1471-2334-6-175.
• [19] CLC and IFNAR1 are differentially expressed and a global immunity score is distinct between early- and late-onset colorectal cancer.Genes Immun. 2011 Dec;12(8):653-62. doi: 10.1038/gene.2011.43. Epub 2011 Jun 30.
• [20] Differences in eosinophil molecular profiles between children and adults with eosinophilic esophagitis.Allergy. 2017 Sep;72(9):1406-1414. doi: 10.1111/all.13140. Epub 2017 Mar 17.
• [21] Identification of key amino acid residues determining ligand binding specificity, homodimerization and cellular distribution of human galectin-10.Glycobiology. 2019 Jan 1;29(1):85-93. doi: 10.1093/glycob/cwy087.
• [22] Cell biology and physiology of CLC chloride channels and transporters.Compr Physiol. 2012 Jul;2(3):1701-44. doi: 10.1002/cphy.c110038.
• [23] A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients.Immunobiology. 2016 Nov;221(11):1227-36. doi: 10.1016/j.imbio.2016.06.012. Epub 2016 Jun 15.
• [24] From tonus to tonicity: physiology of CLC chloride channels.J Am Soc Nephrol. 2000 Jul;11(7):1331-1339. doi: 10.1681/ASN.V1171331.
• [25] Impact of adaptive intensity-modulated radiotherapy on the neutrophil-to-lymphocyte ratio in patients with nasopharyngeal carcinoma.Radiat Oncol. 2019 Aug 22;14(1):151. doi: 10.1186/s13014-019-1350-9.
• [26] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [27] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [28] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [29] Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4578-83.
• [30] 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.
• [31] 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.
• [32] Galectin-10 mRNA is overexpressed in peripheral blood of aspirin-induced asthma. Allergy. 2008 Jan;63(1):125-31. doi: 10.1111/j.1398-9995.2007.01558.x. Epub 2007 Oct 15.