Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC983KJ)

• DOT Name: Galectin-related protein (LGALSL)
• Synonyms: Galectin-like protein; Lectin galactoside-binding-like protein
• Gene Name: LGALSL
• Related Disease:
  Breast cancer
  Breast carcinoma
  Nephrotic syndrome
  Amyotrophic lateral sclerosis
• UniProt ID: LEGL_HUMAN
• PDB ID: 2JJ6; 3B9C
• Pfam ID: PF00337
• Sequence:
  MAGSVADSDAVVKLDDGHLNNSLSSPVQADVYFPRLIVPFCGHIKGGMRPGKKVLVMGIV
  DLNPESFAISLTCGDSEDPPADVAIELKAVFTDRQLLRNSCISGERGEEQSAIPYFPFIP
  DQPFRVEILCEHPRFRVFVDGHQLFDFYHRIQTLSAIDTIKINGDLQITKLG
• Function: Does not bind lactose, and may not bind carbohydrates.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Nephrotic syndrome	DISSPSC2	Strong	Altered Expression	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Unknown	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Galectin-related protein (LGALSL).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Galectin-related protein (LGALSL).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Galectin-related protein (LGALSL).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Galectin-related protein (LGALSL).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Galectin-related protein (LGALSL).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Galectin-related protein (LGALSL).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Galectin-related protein (LGALSL).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Galectin-related protein (LGALSL).	[12]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Galectin-related protein (LGALSL).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Galectin-related protein (LGALSL).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Galectin-related protein (LGALSL).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Galectin-related protein (LGALSL).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Galectin-related protein (LGALSL).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Galectin-related protein (LGALSL).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Galectin-related protein (LGALSL).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Galectin-related protein (LGALSL).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Galectin-related protein (LGALSL).	[18]

References

• [1] HSPC159 promotes proliferation and metastasis by inducing epithelial-mesenchymal transition and activating the PI3K/Akt pathway in breast cancer.Cancer Sci. 2018 Jul;109(7):2153-2163. doi: 10.1111/cas.13631. Epub 2018 Jun 9.
• [2] Gene expression profiling of peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome by cDNA microarrays.Am J Nephrol. 2008;28(4):539-47. doi: 10.1159/000114098. Epub 2008 Jan 25.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] 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.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [14] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [17] 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.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.