Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBOY3WH)

• DOT Name: Kelch repeat and BTB domain-containing protein 11 (KBTBD11)
• Synonyms: Chronic myelogenous leukemia-associated protein; Kelch domain-containing protein 7B
• Gene Name: KBTBD11
• Related Disease:
  Hepatocellular carcinoma
  Colorectal carcinoma
  Nervous system disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Obesity
• UniProt ID: KBTBB_HUMAN
• Pfam ID: PF00651 ; PF01344
• Sequence:
  MEHAVAPCVLYPGTEPGAAGESESEGAASPAQTPCSLGASLCFSSGEESPPQSLASAAEG
  AATSPPSSGGPRVVERQWEAGSAGAASPEELASPEERACPEEPAAPSPEPRVWLEDPASP
  EEPGEPAPVPPGFGAVYGEPDLVLEVSGRRLRAHKAVLAARSDYFRARASRDVLRVQGVS
  LTALRLLLADAYSGRMAGVRPDNVAEVVAGARRLQLPGAAQRATDAVGPQLSLANCYEVL
  SAAKRQRLNELRDAAYCFMSDHYLEVLREPAVFGRLSGAERDLLLRRRLRAGRAHLLAAA
  LGPAGERAGSRPQSPSGDADARGDAAVYCFHAAAGEWRELTRLPEGAPARGCGLCVLYNY
  LFVAGGVAPAGPDGRARPSDQVFCYNPATDSWSAVRPLRQARSQLRLLALDGHLYAVGGE
  CLLSVERYDPRADRWAPVAPLPRGAFAVAHEATTCHGEIYVSGGSLFYRLLKYDPRRDEW
  QECPCSSSRERSADMVALDGFIYRFDLSGSRGEAQAAGPSGVSVSRYHCLAKQWSPCVAP
  LRLPGGPTGLQPFRCAALDGAIYCVSRAGTWRFQPAREGEAGGDAGQGGGFEALGAPLDV
  RGVLIPFALSLPEKPPRGEQGAP

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	moderate	Biomarker	[4]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[4]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[4]
Obesity	DIS47Y1K	moderate	Biomarker	[5]

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 Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[12]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[13]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[18]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Kelch repeat and BTB domain-containing protein 11 (KBTBD11).	[17]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [2] A polymorphic MYC response element in KBTBD11 influences colorectal cancer risk, especially in interaction with an MYC-regulated SNP rs6983267.Ann Oncol. 2018 Mar 1;29(3):632-639. doi: 10.1093/annonc/mdx789.
• [3] Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation.Am J Hum Genet. 2016 May 5;98(5):934-955. doi: 10.1016/j.ajhg.2016.03.027.
• [4] Characterization of Kelch domain-containing protein 7B in breast tumours and breast cancer cell lines.Oncol Lett. 2019 Sep;18(3):2853-2860. doi: 10.3892/ol.2019.10672. Epub 2019 Jul 26.
• [5] Kbtbd11 gene expression in adipose tissue increases in response to feeding and affects adipocyte differentiation.J Diabetes Investig. 2019 Jul;10(4):925-932. doi: 10.1111/jdi.12995. Epub 2019 Jan 25.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] 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.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] 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.
• [13] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [14] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.