Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPW9VRE)

• DOT Name: Clathrin light chain B (CLTB)
• Synonyms: Lcb
• Gene Name: CLTB
• Related Disease:
  Lung cancer
  Lung neoplasm
  Schizophrenia
  Ventricular fibrillation
  Gastric cancer
  Stomach cancer
• UniProt ID: CLCB_HUMAN
• Pfam ID: PF01086
• Sequence:
  MADDFGFFSSSESGAPEAAEEDPAAAFLAQQESEIAGIENDEGFGAPAGSHAAPAQPGPT
  SGAGSEDMGTTVNGDVFQEANGPADGYAAIAQADRLTQEPESIRKWREEQRKRLQELDAA
  SKVTEQEWREKAKKDLEEWNQRQSEQVEKNKINNRIADKAFYQQPDADIIGYVASEEAFV
  KESKEETPGTEWEKVAQLCDFNPKSSKQCKDVSRLRSVLMSLKQTPLSR
• Function: Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
• KEGG Pathway:
  Lysosome (hsa04142)
  Endocytosis (hsa04144)
  Sy.ptic vesicle cycle (hsa04721)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Huntington disease (hsa05016)
  Bacterial invasion of epithelial cells (hsa05100)
• Reactome Pathway:
  Formation of annular gap junctions (R-HSA-196025)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  Lysosome Vesicle Biogenesis (R-HSA-432720)
  WNT5A-dependent internalization of FZD4 (R-HSA-5099900)
  WNT5A-dependent internalization of FZD2, FZD5 and ROR2 (R-HSA-5140745)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Gap junction degradation (R-HSA-190873)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung neoplasm	DISVARNB	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[2]
Ventricular fibrillation	DIS7IN76	moderate	Biomarker	[3]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[4]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[4]

16 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 Clathrin light chain B (CLTB).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Clathrin light chain B (CLTB).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Clathrin light chain B (CLTB).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Clathrin light chain B (CLTB).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Clathrin light chain B (CLTB).	[9]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Clathrin light chain B (CLTB).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Clathrin light chain B (CLTB).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Clathrin light chain B (CLTB).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Clathrin light chain B (CLTB).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Clathrin light chain B (CLTB).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Clathrin light chain B (CLTB).	[15]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Clathrin light chain B (CLTB).	[16]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Clathrin light chain B (CLTB).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Clathrin light chain B (CLTB).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Clathrin light chain B (CLTB).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Clathrin light chain B (CLTB).	[18]

References

• [1] Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents.Oncotarget. 2017 Mar 21;8(12):18885-18900. doi: 10.18632/oncotarget.13806.
• [2] Alterations in oligodendrocyte proteins, calcium homeostasis and new potential markers in schizophrenia anterior temporal lobe are revealed by shotgun proteome analysis.J Neural Transm (Vienna). 2009 Mar;116(3):275-89. doi: 10.1007/s00702-008-0156-y. Epub 2008 Nov 26.
• [3] Breathing changes accompanying balance improvement during biofeedback.Neurosci Lett. 2017 Jun 9;651:30-35. doi: 10.1016/j.neulet.2017.04.051. Epub 2017 Apr 27.
• [4] Expression and clinical significance of autophagic protein LC3B and EMT markers in gastric cancer.Cancer Manag Res. 2018 Jun 11;10:1479-1486. doi: 10.2147/CMAR.S164842. eCollection 2018.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [11] 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.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] An approach to elucidate potential mechanism of renal toxicity of arsenic trioxide. Exp Hematol. 2007 Feb;35(2):252-62.
• [14] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [17] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.