Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRI222R)

• DOT Name: Histone deacetylase 11 (HDAC11)
• Synonyms: HD11; EC 3.5.1.98
• Gene Name: HDAC11
• UniProt ID: HDA11_HUMAN
• EC Number: 3.5.1.98
• Pfam ID: PF00850
• Sequence:
  MLHTTQLYQHVPETRWPIVYSPRYNITFMGLEKLHPFDAGKWGKVINFLKEEKLLSDSML
  VEAREASEEDLLVVHTRRYLNELKWSFAVATITEIPPVIFLPNFLVQRKVLRPLRTQTGG
  TIMAGKLAVERGWAINVGGGFHHCSSDRGGGFCAYADITLAIKFLFERVEGISRATIIDL
  DAHQGNGHERDFMDDKRVYIMDVYNRHIYPGDRFAKQAIRRKVELEWGTEDDEYLDKVER
  NIKKSLQEHLPDVVVYNAGTDILEGDRLGGLSISPAGIVKRDELVFRMVRGRRVPILMVT
  SGGYQKRTARIIADSILNLFGLGLIGPESPSVSAQNSDTPLLPPAVP
• Function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes.
• Tissue Specificity: Weakly expressed in most tissues. Strongly expressed in brain, heart, skeletal muscle, kidney and testis.
• KEGG Pathway:
  Neutrophil extracellular trap formation (hsa04613)
  Alcoholism (hsa05034)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  Notch-HLH transcription pathway (R-HSA-350054)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Histone deacetylase 11 (HDAC11).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Histone deacetylase 11 (HDAC11).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone deacetylase 11 (HDAC11).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone deacetylase 11 (HDAC11).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone deacetylase 11 (HDAC11).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone deacetylase 11 (HDAC11).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone deacetylase 11 (HDAC11).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Histone deacetylase 11 (HDAC11).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Histone deacetylase 11 (HDAC11).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Histone deacetylase 11 (HDAC11).	[6]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Histone deacetylase 11 (HDAC11).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Histone deacetylase 11 (HDAC11).	[10]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [6] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Novel carbocyclic curcumin analog CUR3d modulates genes involved in multiple apoptosis pathways in human hepatocellular carcinoma cells. Chem Biol Interact. 2015 Dec 5;242:107-22.
• [9] 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.
• [10] 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.