Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT73OLML)

• DOT Name: Histone deacetylase complex subunit SAP30 (SAP30)
• Synonyms: 30 kDa Sin3-associated polypeptide; Sin3 corepressor complex subunit SAP30; Sin3-associated polypeptide p30
• Gene Name: SAP30
• UniProt ID: SAP30_HUMAN
• PDB ID: 2KDP
• Pfam ID: PF13867 ; PF13866
• Sequence:
  MNGFTPDEMSRGGDAAAAVAAVVAAAAAAASAGNGTGAGTGAEVPGAGAVSAAGPPGAAG
  PGPGQLCCLREDGERCGRAAGNASFSKRIQKSISQKKVKIELDKSARHLYICDYHKNLIQ
  SVRNRRKRKGSDDDGGDSPVQDIDTPEVDLYQLQVNTLRRYKRHFKLPTRPGLNKAQLVE
  IVGCHFRSIPVNEKDTLTYFIYSVKNDKNKSDLKVDSGVH
• Function: Involved in the functional recruitment of the Sin3-histone deacetylase complex (HDAC) to a specific subset of N-CoR corepressor complexes. Capable of transcription repression by N-CoR. Active in deacetylating core histone octamers (when in a complex) but inactive in deacetylating nucleosomal histones; (Microbial infection) Involved in transcriptional repression of HHV-1 genes TK and gC.
• Tissue Specificity: Expressed in all tissues tested with highest levels in pancreas, ovary, PBL, spleen and thymus; lowest levels in brain, placenta, lung and kidney.
• KEGG Pathway: Epstein-Barr virus infection (hsa05169)
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  Potential therapeutics for SARS (R-HSA-9679191)
  HDACs deacetylate histones (R-HSA-3214815)

Molecular Interaction Atlas (MIA) of This DOT

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 Histone deacetylase complex subunit SAP30 (SAP30).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[7]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[8]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[11]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[12]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[3]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Histone deacetylase complex subunit SAP30 (SAP30).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Histone deacetylase complex subunit SAP30 (SAP30).	[13]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Real-time monitoring of cisplatin-induced cell death. PLoS One. 2011;6(5):e19714. doi: 10.1371/journal.pone.0019714. Epub 2011 May 16.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [9] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.