Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSSUQ3Z)

• DOT Name: Stearoyl-CoA desaturase 5 (SCD5)
• Synonyms: EC 1.14.19.1; Acyl-CoA-desaturase 4; HSCD5; Stearoyl-CoA 9-desaturase; Stearoyl-CoA desaturase 2
• Gene Name: SCD5
• Related Disease:
  Melanoma
  Metastatic melanoma
  Sickle-cell anaemia
  T-cell acute lymphoblastic leukaemia
  Alzheimer disease
  Ankylosing spondylitis
  Breast cancer
  Breast carcinoma
  Cryptococcosis
  Hypertrophic cardiomyopathy
  Immunodeficiency
  Leukemia
  Non-insulin dependent diabetes
  Osteoarthritis
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Age-related macular degeneration
  HIV infectious disease
  Hearing loss, autosomal dominant 79
  Hepatocellular carcinoma
  Neoplasm
  Systemic primary carnitine deficiency disease
• UniProt ID: SCD5_HUMAN
• EC Number: 1.14.19.1
• Pfam ID: PF00487
• Sequence:
  MPGPATDAGKIPFCDAKEEIRAGLESSEGGGGPERPGARGQRQNIVWRNVVLMSLLHLGA
  VYSLVLIPKAKPLTLLWAYFCFLLAALGVTAGAHRLWSHRSYRAKLPLRIFLAVANSMAF
  QNDIFEWSRDHRAHHKYSETDADPHNARRGFFFSHIGWLFVRKHRDVIEKGRKLDVTDLL
  ADPVVRIQRKYYKISVVLMCFVVPTLVPWYIWGESLWNSYFLASILRYTISLNISWLVNS
  AAHMYGNRPYDKHISPRQNPLVALGAIGEGFHNYHHTFPFDYSASEFGLNFNPTTWFIDF
  MCWLGLATDRKRATKPMIEARKARTGDSSA
• Function: Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA. Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids. Involved in neuronal cell proliferation and differentiation through down-regulation of EGFR/AKT/MAPK and Wnt signaling pathways.
• Tissue Specificity: Detected in fetal brain, and at lower levels in fetal kidney. Detected in adult brain and pancreas, and at lower levels in kidney and lung. Expressed in spiral ganglion cells and the organ of Corti of fetal cochlea .
• KEGG Pathway:
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  AMPK sig.ling pathway (hsa04152)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)
  Fatty acyl-CoA biosynthesis (R-HSA-75105)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Altered Expression	[1]
Metastatic melanoma	DISSL43L	Definitive	Altered Expression	[1]
Sickle-cell anaemia	DIS5YNZB	Definitive	Genetic Variation	[2]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[7]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[8]
Immunodeficiency	DIS093I0	Strong	Biomarker	[9]
Leukemia	DISNAKFL	Strong	Biomarker	[10]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[11]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[12]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[13]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[5]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[14]
HIV infectious disease	DISO97HC	moderate	Altered Expression	[15]
Hearing loss, autosomal dominant 79	DISS3787	Limited	Unknown	[16]
Hepatocellular carcinoma	DIS0J828	Limited	Genetic Variation	[17]
Neoplasm	DISZKGEW	Limited	Altered Expression	[1]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Biomarker	[18]

12 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 Stearoyl-CoA desaturase 5 (SCD5).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[22]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[24]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[29]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[30]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Stearoyl-CoA desaturase 5 (SCD5).	[31]

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 Stearoyl-CoA desaturase 5 (SCD5).	[25]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Stearoyl-CoA desaturase 5 (SCD5).	[26]

References

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• [4] Transcriptome differences between the frontal cortex and hippocampus of wild-type and humanized presenilin-1 transgenic mice.Am J Geriatr Psychiatry. 2005 Dec;13(12):1041-51. doi: 10.1176/appi.ajgp.13.12.1041.
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• [9] Retroviral vectors expressing soluble CD4: a potential gene therapy for AIDS.AIDS Res Hum Retroviruses. 1990 Feb;6(2):183-91. doi: 10.1089/aid.1990.6.183.
• [10] Gene transfer of anti-gp41 antibody and CD4 immunoadhesin strongly reduces the HIV-1 load in humanized severe combined immunodeficient mice.AIDS. 2000 Dec 22;14(18):2813-22. doi: 10.1097/00002030-200012220-00002.
• [11] Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
• [12] High concentration of soluble HLA-DR in the synovial fluid: generation and significance in "rheumatoid-like" inflammatory joint diseases.Cell Immunol. 2000 Dec 15;206(2):85-100. doi: 10.1006/cimm.2000.1729.
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• [14] Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration.JCI Insight. 2018 Apr 5;3(7):e120157. doi: 10.1172/jci.insight.120157. eCollection 2018 Apr 5.
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• [16] A de novo microtriplication at 4q21.21-q21.22 in a patient with a vascular malignant hemangioma, elongated sigmoid colon, developmental delay, and absence of speech. Am J Med Genet A. 2016 Aug;170(8):2089-96. doi: 10.1002/ajmg.a.37754. Epub 2016 Jun 10.
• [17] Polymorphisms in the 3'-UTR of SCD5 gene are associated with hepatocellular carcinoma in Korean population.Mol Biol Rep. 2018 Dec;45(6):1705-1714. doi: 10.1007/s11033-018-4313-6. Epub 2018 Aug 30.
• [18] Ciliary ultrastructure in patients with chronic rhinosinusitis and primary ciliary dyskinesia.Eur Arch Otorhinolaryngol. 2013 Jul;270(7):2065-70. doi: 10.1007/s00405-012-2342-7. Epub 2013 Jan 5.
• [19] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [20] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [21] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [22] 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.
• [23] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] 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.
• [26] 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.
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• [29] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.
• [30] Genomic and phenotypic alterations of the neuronal-like cells derived from human embryonal carcinoma stem cells (NT2) caused by exposure to organophosphorus compounds paraoxon and mipafox. Int J Mol Sci. 2014 Jan 9;15(1):905-26. doi: 10.3390/ijms15010905.
• [31] Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway. Chem Biol Interact. 2018 Jun 25;290:77-87.