Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBIN5IP)

• DOT Name: Saccharopine dehydrogenase-like oxidoreductase (SCCPDH)
• Synonyms: EC 1.-.-.-
• Gene Name: SCCPDH
• UniProt ID: SCPDL_HUMAN
• EC Number: 1.-.-.-
• Pfam ID: PF03435
• Sequence:
  MATEQRPFHLVVFGASGFTGQFVTEEVAREQVDPERSSRLPWAVAGRSREKLQRVLEKAA
  LKLGRPTLSSEVGIIICDIANPASLDEMAKQATVVLNCVGPYRFYGEPVIKACIENGASC
  IDISGEPQFLELMQLKYHEKAADKGVYIIGSSGFDSIPADLGVIYTRNKMNGTLTAVESF
  LTIHSGPEGLSIHDGTWKSAIYGFGDQSNLRKLRNVSNLKPVPLIGPKLKRRWPISYCRE
  LKGYSIPFMGSDVSVVRRTQRYLYENLEESPVQYAAYVTVGGITSVIKLMFAGLFFLFFV
  RFGIGRQLLIKFPWFFSFGYFSKQGPTQKQIDAASFTLTFFGQGYSQGTGTDKNKPNIKI
  CTQVKGPEAGYVATPIAMVQAAMTLLSDASHLPKAGGVFTPGAAFSKTKLIDRLNKHGIE
  FSVISSSEV
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

16 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 Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[9]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[3]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[16]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Saccharopine dehydrogenase-like oxidoreductase (SCCPDH).	[13]

References

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• [2] 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.
• [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] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 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.
• [8] 5-Fluorouracil up-regulates interferon pathway gene expression in esophageal cancer cells. Anticancer Res. 2005 Sep-Oct;25(5):3271-8.
• [9] 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.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.