Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6RIOV)

• DTT Name: Acyl-CoA desaturase (SCD)
• Synonyms: hSCD1; Stearoyl-coenzyme A (Delta9) desaturase; Stearoyl-CoA desaturase; Membrane-bound 9 desaturase; Fatty acid desaturase; DesA3; Des A3; Delta-9-stearoyl desaturase; Delta-9 desaturase; Delta(9)-desaturase; 9 stearoyl-desaturase
• Gene Name: SCD
• DTT Type: Successful target; [1]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: ACOD_HUMAN
• TTD ID: T10897
• EC Number: EC 1.14.19.1
• Sequence:
  MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYK
  DKEGPSPKVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAH
  RLWSHRSYKARLPLRLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFS
  HVGWLLVRKHPAVKEKGSTLDLSDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGE
  TFQNSVFVATFLRYAVVLNATWLVNSAAHLFGYRPYDKNISPRENILVSLGAVGEGFHNY
  HHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYDRKKVSKAAILARIKRTGDGNYKSG
• Function: 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. Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation. Plays an important role in body energy homeostasis. Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides. Stearyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates.
• KEGG Pathway: Metabolic pathways (mtc01100)
• Reactome Pathway:
  Fatty acyl-CoA biosynthesis (R-HSA-75105)
  NR1H2 & NR1H3 regulate gene expression linked to lipogenesis (R-HSA-9029558)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Isoxyl	DMJL10P	Bacterial infection	1A00-1C4Z	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aramchol	DMDLGRO	Lipid metabolism disorder	5C52.Z	Phase 2/3	[2]
MK-8245	DMG6KXB	Type-2 diabetes	5A11	Phase 2	[3]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(4-benzoylpiperazin-1-yl)thiazole-5-carboxamide	DMJA5Y4	Discovery agent	N.A.	Investigative	[4]
CVT-12012	DMOCKMZ	Diabetic complication	5A2Y	Investigative	[5]
ISIS 147919	DMTE3FJ	Discovery agent	N.A.	Investigative	[6]
MF-152	DMBLUSA	Discovery agent	N.A.	Investigative	[7]
Sterculic acid	DM1PMR3	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	4.73E-01	0.2	0.54

References

• [1] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [2] The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014 Dec;12(12):2085-91.e1.
• [3] Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia. J Med Chem. 2011 Jul 28;54(14):5082-96.
• [4] Thiazole analog as stearoyl-CoA desaturase 1 inhibitor. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5214-7.
• [5] Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4070-4.
• [6] US patent application no. 7,132,529, Antisense modulation of stearoyl-CoA desaturase expression.
• [7] SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1593-7.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015