Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMVFOT1)

• DOT Name: DEP domain-containing protein 1B (DEPDC1B)
• Synonyms: HBV X-transactivated gene 8 protein; HBV XAg-transactivated protein 8
• Gene Name: DEPDC1B
• Related Disease:
  Breast cancer
  Breast carcinoma
  Cytomegalovirus infection
  Hepatocellular carcinoma
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Oral cancer
  Prostate cancer
  Prostate carcinoma
  Rhabdomyosarcoma
  Advanced cancer
  Malignant soft tissue neoplasm
  Recessive X-linked ichthyosis
  Sarcoma
  Soft tissue sarcoma
• UniProt ID: DEP1B_HUMAN
• Pfam ID: PF00610 ; PF00620
• Sequence:
  MEHRIVGPGPYRATRLWNETVELFRAKMPLRKHRCRFKSYEHCFTAAEAVDWLHELLRCS
  QNFGPEVTRKQTVQLLKKFLKNHVIEDIKGKWGEEDFEDNRHLYRFPPSSPLKPYPKKPP
  NQKDVIKFPEWNDLPPGTSQENIPVRPVVMNSEMWYKRHSIAIGEVPACRLVHRRQLTEA
  NVEEIWKSMTLSYLQKILGLDSLEEVLDVKLVNSKFIIHNVYSVSKQGVVILDDKSKELP
  HWVLSAMKCLANWPNCSDLKQPMYLGFEKDVFKTIADYYGHLKEPLLTFHLFDAFVSVLG
  LLQKEKVAVEAFQICCLLLPPENRRKLQLLMRMMARICLNKEMPPLCDGFGTRTLMVQTF
  SRCILCSKDEVDLDELLAARLVTFLMDNYQEILKVPLALQTSIEERVAHLRRVQIKYPGA
  DMDITLSAPSFCRQISPEEFEYQRSYGSQEPLAALLEEVITDAKLSNKEKKKKLKQFQKS
  YPEVYQERFPTPESAALLFPEKPKPKPQLLMWALKKPFQPFQRTRSFRM
• Reactome Pathway:
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOJ GTPase cycle (R-HSA-9013409)
  RHOU GTPase cycle (R-HSA-9013420)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOV GTPase cycle (R-HSA-9013424)
  RHOF GTPase cycle (R-HSA-9035034)
  RND3 GTPase cycle (R-HSA-9696264)
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

16 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]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Melanoma	DIS1RRCY	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Oral cancer	DISLD42D	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Rhabdomyosarcoma	DISNR7MS	moderate	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Altered Expression	[7]
Recessive X-linked ichthyosis	DISZY56W	Limited	Altered Expression	[7]
Sarcoma	DISZDG3U	Limited	Altered Expression	[7]
Soft tissue sarcoma	DISSN8XB	Limited	Biomarker	[7]

24 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 DEP domain-containing protein 1B (DEPDC1B).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of DEP domain-containing protein 1B (DEPDC1B).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DEP domain-containing protein 1B (DEPDC1B).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of DEP domain-containing protein 1B (DEPDC1B).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of DEP domain-containing protein 1B (DEPDC1B).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[18]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[19]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[20]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[21]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[22]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of DEP domain-containing protein 1B (DEPDC1B).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[23]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[26]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of DEP domain-containing protein 1B (DEPDC1B).	[27]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of DEP domain-containing protein 1B (DEPDC1B).	[28]

References

• [1] High levels of DEPDC1B predict shorter biochemical recurrence-free survival of patients with prostate cancer.Oncol Lett. 2017 Dec;14(6):6801-6808. doi: 10.3892/ol.2017.7027. Epub 2017 Sep 22.
• [2] Human cytomegalovirus-encoded miR-US25-1 aggravates the oxidised low density lipoprotein-induced apoptosis of endothelial cells.Biomed Res Int. 2014;2014:531979. doi: 10.1155/2014/531979. Epub 2014 May 8.
• [3] XTP8 promotes hepatocellular carcinoma growth by forming a positive feedback loop with FOXM1 oncogene.Biochem Biophys Res Commun. 2019 Jul 30;515(3):455-461. doi: 10.1016/j.bbrc.2019.05.164. Epub 2019 Jun 1.
• [4] DEPDC1B knockdown inhibits the development of malignant melanoma through suppressing cell proliferation and inducing cell apoptosis.Exp Cell Res. 2019 Jun 1;379(1):48-54. doi: 10.1016/j.yexcr.2019.03.021. Epub 2019 Mar 14.
• [5] A putative novel protein, DEPDC1B, is overexpressed in oral cancer patients, and enhanced anchorage-independent growth in oral cancer cells that is mediated by Rac1 and ERK.J Biomed Sci. 2014 Aug 5;21(1):67. doi: 10.1186/s12929-014-0067-1.
• [6] DEPDC1B is a key regulator of myoblast proliferation in mouse and man.Cell Prolif. 2020 Jan;53(1):e12717. doi: 10.1111/cpr.12717. Epub 2019 Dec 11.
• [7] Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas.Histol Histopathol. 2018 Jun;33(6):597-608. doi: 10.14670/HH-11-959. Epub 2018 Jan 3.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [13] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [14] 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.
• [15] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [16] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [17] 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.
• [18] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [19] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [20] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [21] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [22] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [23] 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.
• [24] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [25] 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.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [27] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [28] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.