Details of Drug Off-Target (DOT)

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

• DOT Name: Serine dehydratase-like (SDSL)
• Synonyms: L-serine deaminase; L-serine dehydratase/L-threonine deaminase; L-threonine dehydratase; TDH; EC 4.3.1.19; Serine dehydratase 2; SDH 2; EC 4.3.1.17
• Gene Name: SDSL
• UniProt ID: SDSL_HUMAN
• PDB ID: 2RKB
• EC Number: 4.3.1.17; 4.3.1.19
• Pfam ID: PF00291
• Sequence:
  MDGPVAEHAKQEPFHVVTPLLESWALSQVAGMPVFLKCENVQPSGSFKIRGIGHFCQEMA
  KKGCRHLVCSSGGNAGIAAAYAARKLGIPATIVLPESTSLQVVQRLQGEGAEVQLTGKVW
  DEANLRAQELAKRDGWENVPPFDHPLIWKGHASLVQELKAVLRTPPGALVLAVGGGGLLA
  GVVAGLLEVGWQHVPIIAMETHGAHCFNAAITAGKLVTLPDITSVAKSLGAKTVAARALE
  CMQVCKIHSEVVEDTEAVSAVQQLLDDERMLVEPACGAALAAIYSGLLRRLQAEGCLPPS
  LTSVVVIVCGGNNINSRELQALKTHLGQV
• Function: Has low serine dehydratase and threonine dehydratase activity.
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  Cysteine and methionine metabolism (hsa00270)
  Valine, leucine and isoleucine biosynthesis (hsa00290)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway: Threonine catabolism (R-HSA-8849175)
• BioCyc Pathway: MetaCyc:HS06616-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

13 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 Serine dehydratase-like (SDSL).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine dehydratase-like (SDSL).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine dehydratase-like (SDSL).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine dehydratase-like (SDSL).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Serine dehydratase-like (SDSL).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Serine dehydratase-like (SDSL).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine dehydratase-like (SDSL).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine dehydratase-like (SDSL).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Serine dehydratase-like (SDSL).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serine dehydratase-like (SDSL).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine dehydratase-like (SDSL).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Serine dehydratase-like (SDSL).	[12]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Serine dehydratase-like (SDSL).	[13]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.