Larsucosterol (DUR-928) trimethylamine is a cholesterol metabolite and a potent liver X receptor (LXR) antagonist. Larsucosterol trimethylamine is a potent modulator of endogenous lipogenesis. Larsucosterol trimethylamine inhibits cholesterol biosynthesis by reducing mRNA levels and inhibiting SREBP-1 activation.

Physicochemical Properties

Molecular Formula	C30H46O5S.0.45C3H9N
Molecular Weight	509.32
Related CAS #	Larsucosterol;884905-07-1;Larsucosterol sodium;1174047-40-5
Appearance	Solid powder
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	In HepG2 cells, leucosterol (DUR-928; 0–25 μM; 8 h) Due to a dose-dependent reduction in free [14C] cholesterol, trimethylamine inhibits the production of cholesterol by lowering HMG-CoA reductase mRNA levels[1]. Larsucosterol (0–25 μM; 6 hours; HepG2 cells) By suppressing SREBP1 expression and activation in hepatocytes, trimethylamine reduces the expression of HMG-CoA reductase[1]. 48 hours; 0–50 μM) of levocosterol Macrophage apoptosis is reduced and cell proliferation is increased by trimethylamine[2]. 0–25 μM; 48 hours; macrophages) The liver oxysterol receptor LXRα is inhibited by trimethylamine [2].
ln Vivo	In mice fed a high-fat diet, levigocosterol (DUR-928; 25 mg/kg; ip; twice in 14 hours; C57BL/6J mice with nonalcoholic fatty liver disorders (NAFLD) model) trimethylamine lowers serum lipid levels[3]. (25 mg/kg; intraperitoneally; twice in 14 hours; C57BL/6J mice with nonalcoholic fatty liver disease (NAFLD) model) decreases the expression of ABCA1 and suppresses gene expression. Larsucosterol reduces the amounts of cytoplasmic FAS and ACC1 protein, as well as nuclear SREBP-1 protein, in liver tissue[3]. Trimethylamine and lansucosterol (25 mg/kg; ip; once every three days for six weeks; C57BL/6J mice with nonalcoholic fatty liver disorders (NAFLD) model) prevent liver damage by reducing hepatic inflammation[3].
Cell Assay	Cell Proliferation Assay[2] Cell Types: Macrophages Tested Concentrations: 0, 5, 10, 15, 20, and 25 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induces cell proliferation and relative cell number after treatment for 48 h were 120% at 25 μM. Apoptosis Analysis[2] Cell Types: Macrophages Tested Concentrations: 0, 10, 20, 30, 40 and 50 μM Incubation Duration: 48 hrs (hours) Experimental Results: Did not Dramatically affect the numbers of apoptotic or live cells. Western Blot Analysis[1] Cell Types: HepG2 cells Tested Concentrations: 0, 3, 6, 12, and 25 μM Incubation Duration: 6 hrs (hours) Experimental Results: Inhibited the activation of SREBP-1 and SREBP-2, and subsequently inhibited the expression HMG-CoA reductase. Western Blot Analysis[2] Cell Types: Macrophages Tested Concentrations: 0, 3, 6, 12, and 25 μM Incubation Duration: 48 hrs (hours) Experimental Results: diminished LXRα levels in the nuclei in a does-dependent manner.
Animal Protocol	Animal/Disease Models: Female C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model[3] Doses: 25 mg/kg Route of Administration: intraperitoneal (ip)injection; twice in 14 hrs (hours) Experimental Results: diminished plasma TG, CHOL, and HDL -C by 40, 15, and 20%, respectively. decreased the mRNA levels of SREBP-1c, ACC1, and FAS by 46, 57, and 49%, respectively. Suppressed ABCA1 expression. Suppressed nuclear SREBP-1, cytoplasmic ACC1, and FAS protein levels by 74, 58, and 47%, respectively. Animal/Disease Models: Female C57BL/6J mice with nonalcoholic fatty liver diseases (NAFLD) model[3] Doses: 25 mg/kg Route of Administration: intraperitoneal (ip)injection; once every 3 days for 6 weeks Experimental Results: diminished plasma cholesterol levels. decreased serum alkaline phosphatase, ALT, and AST levels.
References	[1]. Sulfated oxysterol, 25HC3S, is a potent regulator of lipid metabolism in human hepatocytes. Biochem Biophys Res Commun. 2007 Sep 7;360(4):802-8. [2]. 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1369-79. [3]. 5-cholesten-3β,25-diol 3-sulfate decreases lipid accumulation in diet-induced nonalcoholic fatty liver disease mouse model. Mol Pharmacol. 2013 Mar;83(3):648-58.

Solubility Data

Solubility (In Vitro)

DMSO :~33.33 mg/mL (~65.44 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9634 mL	9.8170 mL	19.6340 mL
	5 mM	0.3927 mL	1.9634 mL	3.9268 mL
	10 mM	0.1963 mL	0.9817 mL	1.9634 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.