Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0W0M0L)

• DOT Name: C-type lectin domain family 2 member B (CLEC2B)
• Synonyms: Activation-induced C-type lectin; C-type lectin superfamily member 2; IFN-alpha-2b-inducing-related protein 1
• Gene Name: CLEC2B
• Related Disease:
  Haematological malignancy
  Liver cancer
  Neoplasm
• UniProt ID: CLC2B_HUMAN
• Pfam ID: PF00059
• Sequence:
  MMTKHKKCFIIVGVLITTNIITLIVKLTRDSQSLCPYDWIGFQNKCYYFSKEEGDWNSSK
  YNCSTQHADLTIIDNIEEMNFLRRYKCSSDHWIGLKMAKNRTGQWVDGATFTKSFGMRGS
  EGCAYLSDDGAATARCYTERKWICRKRIH
• Tissue Specificity: Expressed preferentially in lymphoid tissues, and in most hematopoietic cell types.
• KEGG Pathway: Kaposi sarcoma-associated herpesvirus infection (hsa05167)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Haematological malignancy	DISCDP7W	Strong	Biomarker	[1]
Liver cancer	DISDE4BI	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

14 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 C-type lectin domain family 2 member B (CLEC2B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-type lectin domain family 2 member B (CLEC2B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C-type lectin domain family 2 member B (CLEC2B).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of C-type lectin domain family 2 member B (CLEC2B).	[5]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of C-type lectin domain family 2 member B (CLEC2B).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of C-type lectin domain family 2 member B (CLEC2B).	[7]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of C-type lectin domain family 2 member B (CLEC2B).	[8]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of C-type lectin domain family 2 member B (CLEC2B).	[9]
Atenolol	DMNKG1Z	Approved	Atenolol increases the expression of C-type lectin domain family 2 member B (CLEC2B).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of C-type lectin domain family 2 member B (CLEC2B).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-type lectin domain family 2 member B (CLEC2B).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of C-type lectin domain family 2 member B (CLEC2B).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of C-type lectin domain family 2 member B (CLEC2B).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of C-type lectin domain family 2 member B (CLEC2B).	[15]

1 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 C-type lectin domain family 2 member B (CLEC2B).	[11]

References

• [1] Tumor cells of non-hematopoietic and hematopoietic origins express activation-induced C-type lectin, the ligand for killer cell lectin-like receptor F1.Int Immunol. 2010 Sep;22(9):783-90. doi: 10.1093/intimm/dxq430. Epub 2010 Jul 26.
• [2] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [6] 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.
• [7] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [8] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [9] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [10] Change in mRNA Expression after Atenolol, a Beta-adrenergic Receptor Antagonist and Association with Pharmacological Response. Arch Drug Inf. 2009 Sep;2(3):41-50. doi: 10.1111/j.1753-5174.2009.00020.x.
• [11] 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.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.