SB-201076
SB-201076 is an orally active inhibitor of ATP citrate lyase (Ki=1 μM). SB-201076 is applicable to research related to hyperlipidemia and cancer.
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- CAS No.: 154566-05-9
- Formule: C18H24Cl2O6
- Masse moléculaire:407.29
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
SB-201076 (20 min) potently and equally inhibits purified rat liver ATP citrate-lyase and recombinant human ATP citrate-lyase with a Ki of 1 µM[1].
SB-201076 (1 mM; 2.5 h) does not inhibit cholesterol or fatty acid synthesis in Hep G2 cells at concentrations up to 1 mM[1].
SB-201076 potently inhibits recombinant rat and human ATP citrate lyase with a Ki of 1 μM, acting competitively against citrate and noncompetitively against CoA[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
SB-201076 (150 µmol/kg; i.v.; two doses administered 245 and 65 minutes prior to 3H2O injection) is delivered via intravenous administration of SB-204990 to rat liver, inhibiting hepatic cholesterol synthesis by 76% and hepatic fatty acid synthesis by 39%[1].
SB-201076 (10-25 mg/kg per day; p.o.; daily; 22 days) is delivered via chronic oral administration of SB-204990 to beagle dogs, resulting in sustained decreases in plasma cholesterol (up to 23%), plasma triglycerides (up to 38%), LDL cholesterol (40%), and HDL cholesterol (22%) over 22 days[1].
SB-201076 (p.o.) dose-dependently reduces plasma cholesterol by up to 46% and plasma triglycerides by up to 80% in rats[2].
SB-201076 (p.o.) dose-dependently reduces plasma cholesterol by up to 23% and plasma triglycerides by up to 38% in dogs[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male, 200-250 g body weight, maintained on reverse light cycle for 2 weeks prior to study)[1]
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Dosage:150 µmol/kg (delivered as SB-204990)
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Administration:p.o.; single dose
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Result:Reached maximal plasma concentration of 41 nmol/mL at 4 hours after dosing.
Reached maximal hepatic concentration of 87 nmol/g at 4 hours after dosing, a level sufficient to inhibit ATP citrate-lyase relative to its Kᵢ of 1 μM.
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Animal Model:Sprague-Dawley (male, starting body weight ~180 g, range 166-193 g, maintained on reverse light cycle for 2 weeks prior to study)[1]
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Dosage:0.05% (w/w) in diet (156 µmol/day per kg); 0.125% (w/w) in diet (382 µmol/day per kg); 0.25% (w/w) in diet (729 µmol/day per kg) (delivered as SB-204990)
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Administration:p.o.; daily; 7 days
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Result:Achieved dose-related hepatic concentrations of SB-204990 (converted to SB-201076) of 60-103 nmol/g, sufficient to inhibit ATP citrate-lyase.
Decreased plasma cholesterol by up to 46% at 0.25% w/w dose.
Decreased plasma triglycerides by up to 80% at 0.25% w/w dose.
Decreased VLDL synthesis by up to 48% at 0.125% w/w dose.
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Animal Model:Sprague-Dawley (male, maintained on reverse light cycle for 2 weeks prior to study)[1]
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Dosage:150 µmol/kg (delivered as SB-204990)
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Administration:i.v.; two doses administered 245 and 65 minutes prior to 3H2O injection
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Result:Inhibited hepatic cholesterol synthesis by 76% relative to control rats.
Inhibited hepatic fatty acid synthesis by 39% relative to control rats.
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Animal Model:Beagle (male, housed two per pen)[1]
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Dosage:10 mg/kg per day (delivered as SB-204990, daily for 7 days); 25 mg/kg per day (delivered as SB-204990, daily for 15 days)
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Administration:p.o.; daily; 22 days
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Result:Decreased plasma cholesterol by up to 23% at 25 mg/kg per day dose.
Decreased plasma triglycerides by up to 38% at 25 mg/kg per day dose.
Decreased LDL cholesterol by 40%.
Decreased HDL cholesterol by 22%, with a proportionately greater effect on LDL relative to HDL.
Chemical Information
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CAS No. 154566-05-9
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Masse moléculaire 407.29
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Formule C18H24Cl2O6
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SMILES
OC(C[C@](C(O)=O)(O)C[C@@H](O)CCCCCCC1=C(C=C(C=C1)Cl)Cl)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Pearce NJ, et al. The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076. The Biochemical journal. 1998 Aug 15;334 ( Pt 1)(Pt 1):113-9. [Content Brief]
[2]. Zu XY, et al. ATP citrate lyase inhibitors as novel cancer therapeutic agents. Recent patents on anti-cancer drug discovery. 2012 May 01;7(2):154-67. [Content Brief]
[3]. Zhang L, et al. Opportunities and Challenges for Inhibitors Targeting Citrate Transport and Metabolism in Drug Discovery. Journal of medicinal chemistry. 2023 Jul 27;66(14):9229-9250. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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