Details of Drug Off-Target (DOT)

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

• DOT Name: 3-oxoacyl- synthase, mitochondrial (OXSM)
• Synonyms: EC 2.3.1.41; Beta-ketoacyl-ACP synthase
• Gene Name: OXSM
• UniProt ID: OXSM_HUMAN
• PDB ID: 2C9H; 2IWY; 2IWZ
• EC Number: 2.3.1.41
• Pfam ID: PF00109 ; PF02801
• Sequence:
  MSNCLQNFLKITSTRLLCSRLCQQLRSKRKFFGTVPISRLHRRVVITGIGLVTPLGVGTH
  LVWDRLIGGESGIVSLVGEEYKSIPCSVAAYVPRGSDEGQFNEQNFVSKSDIKSMSSPTI
  MAIGAAELAMKDSGWHPQSEADQVATGVAIGMGMIPLEVVSETALNFQTKGYNKVSPFFV
  PKILVNMAAGQVSIRYKLKGPNHAVSTACTTGAHAVGDSFRFIAHGDADVMVAGGTDSCI
  SPLSLAGFSRARALSTNSDPKLACRPFHPKRDGFVMGEGAAVLVLEEYEHAVQRRARIYA
  EVLGYGLSGDAGHITAPDPEGEGALRCMAAALKDAGVQPEEISYINAHATSTPLGDAAEN
  KAIKHLFKDHAYALAVSSTKGATGHLLGAAGAVEAAFTTLACYYQKLPPTLNLDCSEPEF
  DLNYVPLKAQEWKTEKRFIGLTNSFGFGGTNATLCIAGL
• Function: May play a role in the biosynthesis of lipoic acid as well as longer chain fatty acids required for optimal mitochondrial function.
• Tissue Specificity: Widely expressed. Higher expression in heart, skeletal muscle, liver and kidney which contain high levels of active mitochondria.
• KEGG Pathway:
  Fatty acid biosynthesis (hsa00061)
  Biotin metabolism (hsa00780)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  Biosynthesis of cofactors (hsa01240)
• BioCyc Pathway: MetaCyc:HS07707-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of 3-oxoacyl- synthase, mitochondrial (OXSM).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[6]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 3-oxoacyl- synthase, mitochondrial (OXSM).	[11]

References

• [1] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.