Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMSVI7R)

• DOT Name: Galectin-7 (LGALS7)
• Synonyms: Gal-7; HKL-14; PI7; p53-induced gene 1 protein
• Gene Name: LGALS7
• Related Disease:
  Acne vulgaris
  Asthma
  Anal intraepithelial neoplasia
  Basal cell carcinoma
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Classic galactosemia
  Colon carcinoma
  Cryptococcosis
  Endometrial cancer
  Endometrial carcinoma
  Galactosemia
  Gastric cancer
  Gastric neoplasm
  Head-neck squamous cell carcinoma
  Lymphoma, non-Hodgkin, familial
  Non-hodgkin lymphoma
  Stomach cancer
  Systemic sclerosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adult lymphoma
  Atrial septal defect
  Autism spectrum disorder
  Congenital glaucoma
  Juvenile open angle glaucoma
  Lymphoma
  Melanoma
  Neuroblastoma
  Pediatric lymphoma
  Cervical cancer
  Cervical carcinoma
  Undifferentiated carcinoma
  Epithelial ovarian cancer
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: LEG7_HUMAN
• PDB ID: 1BKZ ; 2GAL ; 3GAL ; 3ZXE ; 3ZXF ; 4GAL ; 4UW3 ; 4UW4 ; 4UW5 ; 4UW6 ; 4XBQ ; 4Y26 ; 5GAL ; 5H9Q ; 5H9S ; 6VTO ; 6VTP ; 6VTQ ; 6VTR ; 6VTS ; 7N4O ; 7N57 ; 7N6C ; 7N8D ; 7N8G ; 7N96 ; 7RDG ; 7TKW ; 7TKX ; 7TKY ; 7TKZ ; 7TRN ; 7TRO ; 7XAC ; 7XBL
• Pfam ID: PF00337
• Sequence:
  MSNVPHKSSLPEGIRPGTVLRIRGLVPPNASRFHVNLLCGEEQGSDAALHFNPRLDTSEV
  VFNSKEQGSWGREERGPGVPFQRGQPFEVLIIASDDGFKAVVGDAQYHHFRHRLPLARVR
  LVEVGGDVQLDSVRIF
• Function: Could be involved in cell-cell and/or cell-matrix interactions necessary for normal growth control. Pro-apoptotic protein that functions intracellularly upstream of JNK activation and cytochrome c release.
• Tissue Specificity: Mainly expressed in stratified squamous epithelium.

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acne vulgaris	DISKW8PI	Definitive	Biomarker	[1]
Asthma	DISW9QNS	Definitive	Biomarker	[2]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Biomarker	[3]
Basal cell carcinoma	DIS7PYN3	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Altered Expression	[8]
Classic galactosemia	DISX7P8M	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[11]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[12]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[12]
Galactosemia	DIS6V2Q3	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[13]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[14]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[15]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[15]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[16]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[5]
Adult lymphoma	DISK8IZR	moderate	Altered Expression	[17]
Atrial septal defect	DISJT76B	moderate	Biomarker	[18]
Autism spectrum disorder	DISXK8NV	moderate	Biomarker	[18]
Congenital glaucoma	DISHN3GO	moderate	Biomarker	[18]
Juvenile open angle glaucoma	DISZ43T5	moderate	Biomarker	[18]
Lymphoma	DISN6V4S	moderate	Altered Expression	[17]
Melanoma	DIS1RRCY	moderate	Altered Expression	[19]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[20]
Pediatric lymphoma	DIS51BK2	moderate	Altered Expression	[17]
Cervical cancer	DISFSHPF	Disputed	Altered Expression	[21]
Cervical carcinoma	DIST4S00	Disputed	Altered Expression	[21]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[22]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[23]
Neoplasm	DISZKGEW	Limited	Altered Expression	[8]
Prostate cancer	DISF190Y	Limited	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[24]

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 Galectin-7 (LGALS7).	[25]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Galectin-7 (LGALS7).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Galectin-7 (LGALS7).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Galectin-7 (LGALS7).	[26]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Galectin-7 (LGALS7).	[28]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Galectin-7 (LGALS7).	[29]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Galectin-7 (LGALS7).	[29]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Galectin-7 (LGALS7).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Galectin-7 (LGALS7).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Galectin-7 (LGALS7).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Galectin-7 (LGALS7).	[33]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Galectin-7 (LGALS7).	[34]

References

• [1] Clinical significance of neutrophil gelatinase-associated lipocalin and galectin-7 in tape-stripped stratum corneum of acne vulgaris.J Dermatol. 2018 May;45(5):618-621. doi: 10.1111/1346-8138.14261. Epub 2018 Feb 22.
• [2] Silencing of Gal-7 inhibits TGF-(1)-induced apoptosis of human airway epithelial cells through JNK signaling pathway.Exp Cell Res. 2019 Feb 15;375(2):100-105. doi: 10.1016/j.yexcr.2018.12.017. Epub 2018 Dec 27.
• [3] Roles of galectin-7 and S100A9 in cervical squamous carcinoma: Clinicopathological and in vitro evidence.Int J Cancer. 2013 Mar 1;132(5):1051-9. doi: 10.1002/ijc.27764. Epub 2012 Aug 28.
• [4] Galectin-7: will the lectin's activity establish clinical correlations in head and neck squamous cell and basal cell carcinomas?.Histol Histopathol. 2009 Jan;24(1):41-8. doi: 10.14670/HH-24.41.
• [5] Sensitizing effect of galectin-7 in urothelial cancer to cisplatin through the accumulation of intracellular reactive oxygen species.Cancer Res. 2007 Feb 1;67(3):1212-20. doi: 10.1158/0008-5472.CAN-06-3283.
• [6] Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7.PLoS One. 2017 Nov 8;12(11):e0187194. doi: 10.1371/journal.pone.0187194. eCollection 2017.
• [7] Galectin-7 Expression Potentiates HER-2-Positive Phenotype in Breast Cancer.PLoS One. 2016 Nov 30;11(11):e0166731. doi: 10.1371/journal.pone.0166731. eCollection 2016.
• [8] Galectin-7 in Epithelial Homeostasis and Carcinomas.Int J Mol Sci. 2017 Dec 19;18(12):2760. doi: 10.3390/ijms18122760.
• [9] The unfolded protein response has a protective role in yeast models of classic galactosemia.Dis Model Mech. 2014 Jan;7(1):55-61. doi: 10.1242/dmm.012641. Epub 2013 Sep 25.
• [10] Suppression of tumor growth by galectin-7 gene transfer.Cancer Res. 2004 Aug 15;64(16):5672-6. doi: 10.1158/0008-5472.CAN-04-0985.
• [11] Isolation of conditional mutations in genes essential for viability of Cryptococcus neoformans.Curr Genet. 2017 Jun;63(3):519-530. doi: 10.1007/s00294-016-0659-2. Epub 2016 Oct 25.
• [12] Galectin-7 is elevated in endometrioid (type I) endometrial cancer and promotes cell migration.Oncol Lett. 2018 Oct;16(4):4721-4728. doi: 10.3892/ol.2018.9193. Epub 2018 Jul 23.
• [13] Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer.Oncotarget. 2013 Sep;4(9):1461-71. doi: 10.18632/oncotarget.1219.
• [14] HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.Theranostics. 2018 Jun 13;8(14):3841-3855. doi: 10.7150/thno.25784. eCollection 2018.
• [15] Galectin-7 in lymphoma: elevated expression in human lymphoid malignancies and decreased lymphoma dissemination by antisense strategies in experimental model.Cancer Res. 2007 Mar 15;67(6):2824-9. doi: 10.1158/0008-5472.CAN-06-3891.
• [16] A potential contribution of decreased galectin-7 expression in stratified epithelia to the development of cutaneous and oesophageal manifestations in systemic sclerosis.Exp Dermatol. 2019 May;28(5):536-542. doi: 10.1111/exd.13900.
• [17] Increased galectin-7 gene expression in lymphoma cells is under the control of DNA methylation.Biochem Biophys Res Commun. 2009 Sep 25;387(3):425-9. doi: 10.1016/j.bbrc.2009.07.015. Epub 2009 Jul 9.
• [18] Familial transmission risk of infantile glaucoma in Australia.Ophthalmic Genet. 2006 Sep;27(3):93-7. doi: 10.1080/13816810600870843.
• [19] Expression and functions of galectin-7 in human and murine melanomas.PLoS One. 2013 May 3;8(5):e63307. doi: 10.1371/journal.pone.0063307. Print 2013.
• [20] Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells.Oncogene. 2003 Sep 18;22(40):6277-88. doi: 10.1038/sj.onc.1206631.
• [21] Profiling protein markers associated with the sensitivity to concurrent chemoradiotherapy in human cervical carcinoma.J Proteome Res. 2009 Aug;8(8):3969-76. doi: 10.1021/pr900287a.
• [22] Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
• [23] Clinical significance of galectin-7 in epithelial ovarian cancer.Anticancer Res. 2013 Apr;33(4):1555-61.
• [24] A Mutation in the Carbohydrate Recognition Domain Drives a Phenotypic Switch in the Role of Galectin-7 in Prostate Cancer.PLoS One. 2015 Jul 13;10(7):e0131307. doi: 10.1371/journal.pone.0131307. eCollection 2015.
• [25] 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.
• [26] 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.
• [27] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [28] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [29] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [30] 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.
• [31] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [32] 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.
• [33] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [34] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.