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Literature summary for 1.14.19.1 extracted from

  • Lyn, R.K.; Singaravelu, R.; Kargman, S.; OHara, S.; Chan, H.; Oballa, R.; Huang, Z.; Jones, D.M.; Ridsdale, A.; Russell, R.S.; Partridge, A.W.; Pezacki, J.P.
    Stearoyl-CoA desaturase inhibition blocks formation of hepatitis C virus-induced specialized membranes (2014), Sci. Rep., 4, 4549 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene scd1, quantitative real-time PCR expression analysis Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2-(1-(3,4,5-trichlorobenzyl)-1H-1,2,3-triazol-4-yl)imidazo[1,2-a]pyridin-7-yl)methanol
-
Homo sapiens
(3(2)R,3(5)S,5S)-5-(tert-butyl)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-4,7-dioxo-2,8-dioxa-6-aza-1(1,7)-isoquinolina-3(2,1)-pyrrolidinacyclotridecaphane-3(5)-carboxamide
-
Homo sapiens
(5-(6-(3-(2-(trifluoromethyl)phenoxy)azetidin-1-yl)pyridazin-3-yl)-1,3,4-oxadiazol-2-yl)methanol
-
Homo sapiens
(5-(6-(4-(2-(trifluoromethyl)phenoxy)piperidin-1-yl)pyridazin-3-yl)-1,3,4-oxadiazol-2-yl)methanol
-
Homo sapiens
(5-(6-(4-(2-bromo-5-fluorophenoxy)piperidin-1-yl)pyridazin-3-yl)pyridin-3-yl)methanol
-
Homo sapiens
5-(4-(2-bromo-5-fluorophenoxy)piperidin-1-yl)thiazolo[5,4-d]pyrimidin-2-amine
-
Homo sapiens
additional information no inhibition by NS3 protease inhibitor B. Palmitoleic acid or oleic acid treatment rescues SCD inhibitors' antiviral effect Homo sapiens
N-(2-(7-((4-chloro-3-(trifluoromethyl)benzyl)amino)-3-(4-methoxyphenyl)-2-oxoquinoxalin-1(2H)-yl)ethyl)acetamide
-
Homo sapiens
[3-(2-[4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl]-1,3-thiazol-5-yl)-1,2,4-oxadiazol-5-yl]methanol EC50 value is 62 nM. SCD-1 inhibition with the inhibitor increases susceptibility of hepatitis C virus RNA to exogenously added nucleases in digitonin permeabilized cells. Low dose treatment with the inhibitor decreases the number of membranous webs and alters their structure while having no effect on lipid droplets in Huh7-SGR cells Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane
-
Homo sapiens 16020
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ Homo sapiens
-
palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O
-
?
stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ Homo sapiens
-
oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens O00767
-
-

Source Tissue

Source Tissue Comment Organism Textmining
Hep-G2 cell
-
Homo sapiens
-
hepatoma cell
-
Homo sapiens
-
Huh-7 cell harboring the pFKI389neo/NS3-39/5.1 subgenomic replicon (Huh7 SGR, genotype 1b) Homo sapiens
-
Huh-7.5 cell stably expressing the full-length HCV genotype 1b replicon with a S2204I adaptive mutation in NS5A (Huh7.5 FGR) Homo sapiens
-
liver high expression level of isozyme SCD-1 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+
-
Homo sapiens palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O
-
?
stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+
-
Homo sapiens oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O
-
?

Synonyms

Synonyms Comment Organism
SCD-1
-
Homo sapiens
stearoyl-CoA desaturase
-
Homo sapiens
stearoyl-CoA desaturase 1
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
in vivo assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
cytochrome b5
-
Homo sapiens

General Information

General Information Comment Organism
malfunction stearoyl-CoA desaturase 1 (SCD-1) inhibition blocks hepatitis C virus replication and formation of hepatitis C virus-induced specialized membranes. Inhibition of stearoyl-CoA desaturase 1 halts the biosynthesis of unsaturated fatty acids, such as oleic acid, and negatively modulates HCV replication. Unsaturated fatty acids play key roles in membrane curvature and fluidity, SCD-1 inhibition disrupts the integrity of membranous HCV replication complexes and renders HCV RNA susceptible to nuclease-mediated degradation Homo sapiens
physiological function stearoyl-CoA desaturase is a key enzyme in the biosynthesis of oleic acid, role of SCD-1 in the fatty acid biosynthesis pathway, schematic overview. SCD-1 catalyzes the fatty acids desaturation at carbon-9 forming a cis-double bond. The SCD-1 produced products, palmitoleoyl-CoA (C16:1) and oleoyl-CoA (C18:1), are directly incorporated in triglycerides, cholesterol esters, and phospholipids. These lipids are crucial to the formation of cytosolic lipid droplets, luminal lipid domains, and lipid-rich membranes, which are platforms for hepatitis C virus replication and assembly. Analysis of the influence of SCD-1 on the nuclease and detergent resistant properties of viral RNA at replication complexes Homo sapiens