SB 204990, the prodrug of the ATP citrate-lyase inhibitor SB-201076, is a potent, orally available and specific inhibitor of ATP citrate lyase (ACLY) enzyme. SB-204990 (25 mg/kg per day) also decreased plasma cholesterol levels (by up to 23%) and triglyceride levels (by up to 38%) in the dog, preferentially decreasing low-density lipoprotein compared with high-density lipoprotein cholesterol levels. SB-204990 is an important enzyme in controlling substrate supply for lipid synthesis de novo and a potential enzyme target for hypolipidaemic intervention.

Physicochemical Properties

Molecular Formula	C18H22CL2O5
Molecular Weight	389.2703
Exact Mass	388.084
CAS #	154566-12-8
PubChem CID	10340264
Appearance	White to off-white solid powder
LogP	4.007
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	9
Heavy Atom Count	25
Complexity	472
Defined Atom Stereocenter Count	2
SMILES	C1[C@H](OC(=O)[C@]1(CC(=O)O)O)CCCCCCC2=C(C=C(C=C2)Cl)Cl
InChi Key	YTRNLFYTHYWDAU-RDTXWAMCSA-N
InChi Code	InChI=1S/C18H22Cl2O5/c19-13-8-7-12(15(20)9-13)5-3-1-2-4-6-14-10-18(24,11-16(21)22)17(23)25-14/h7-9,14,24H,1-6,10-11H2,(H,21,22)/t14-,18-/m1/s1
Chemical Name	trans-5-[6-(2,4-Dichlorophenyl)hexyl]tetrahydro-3-hydroxy-2-oxo-3-furanacetic acid
Synonyms	SB-204990; SB 204990; SB204990
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	The ACLY enzyme is specifically inhibited by SB204990 (SB). Acetylation and active β-catenin levels are predicted to decrease as a result of SB204990 therapy, which lowers cytosolic Ac-CoA levels [1].
ln Vivo	Oral administration of SB 204990 to rats results in its absorption into the systemic circulation. Rats given SB 204990 in the diet (0.05-0.25%, w/w) for one week experienced dose-related decreases in plasma cholesterol (up to 46%) and triglyceride levels (up to 80%). By preferentially lowering LDL cholesterol levels over HDL cholesterol levels, SB 204990 (25 mg/kg daily) also lowers triglyceride levels (up to 38%) and plasma cholesterol levels (up to 23%) in dogs [2].
References	[1]. Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation. J Biol Chem. 2018 Oct 12;293(41):16019-16027. [2]. 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. Biochem J. 1998 Aug 15;334 ( Pt 1):113-9.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~256.89 mM) H2O : ~25 mg/mL (~64.22 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 2.56 mg/mL (6.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5689 mL	12.8446 mL	25.6891 mL
	5 mM	0.5138 mL	2.5689 mL	5.1378 mL
	10 mM	0.2569 mL	1.2845 mL	2.5689 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.