Pradigastat (formerly also known as LCQ-908; LCQ908) is a novel, potent and orally bioavailable diacylglycerol acyltransferase 1 (DGAT1) inhibitor being developed for the treatment of familial chylomicronemia syndrome. It is also being studied in phase II clinical trials as an anti-obesity and anti-diabetic agent. Familial chylomicronemia syndrome (FCS) is a rare lipid disease caused by complete lipoprotein lipase (LPL) deficiency resulting in fasting chylomicronemia and severe hypertriglyceridemia. Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which mediates chylomicron triglyceride (TG) synthesis, is an attractive strategy to reduce TG levels in FCS .

Physicochemical Properties

Molecular Formula	C25H24F3N3O2
Molecular Weight	455.4722
Exact Mass	455.182
CAS #	956136-95-1
Related CAS #	956136-95-1 (free acid);956136-98-4 (sodium);
PubChem CID	53387035
Appearance	Light yellow to yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	611.0±55.0 °C at 760 mmHg
Flash Point	323.3±31.5 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.582
LogP	6.1
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	6
Heavy Atom Count	33
Complexity	631
Defined Atom Stereocenter Count	0
InChi Key	GXALXAKNHIROPE-CALCHBBNSA-N
InChi Code	InChI=1S/C25H24F3N3O2/c26-25(27,28)23-12-10-21(15-30-23)31-20-9-11-22(29-14-20)19-7-5-18(6-8-19)17-3-1-16(2-4-17)13-24(32)33/h5-12,14-17,31H,1-4,13H2,(H,32,33)/t16-,17+
Chemical Name	2-((1s,4s)-4-(4-(5-((6-(trifluoromethyl)pyridin-3-yl)amino)pyridin-2-yl)phenyl)cyclohexyl)acetic acid
Synonyms	LCQ908; LCQ-908; LCQ 908
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	In human ovarian cancer cell lines that overexpress BCRP, prediastat suppresses the protein's dose-dependent efflux activity, with an IC50 value of 5 μM. Estimated IC50 values for pradigastat's concentration-dependent inhibition of OATP1B1, OATP1B3, and OAT3 are 1.66 μM, 3.34 μM, and 0.973 μM, respectively [2].
ln Vivo	In rats, dogs, and monkeys, digastat (LCQ-908) lowers their postprandial triglyceride levels. Rats with no longer having lipoprotein lipase (LPL) activity have less postprandial plasma triglyceride buildup when given pradigastat. Pradigastat reduces the size of chylomicrons and the postprandial rate of chylomicron triglyceride (CM -TG) secretion into the lymphatic duct[3].
References	[1]. Meyers CD, et al. Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome. Lipids Health Dis. 2015 Feb 18;14:8. [2]. Kulmatycki K, et al. Evaluation of a potential transporter-mediated drug interaction between ZD 4522 and pradigastat, a novel DGAT-1 inhibitor. Int J Clin Pharmacol Ther. 2015 May;53(5):345-55. [3]. Charles DanielMeyersMD, et al. The DGAT1 inhibitor pradigastat decreases chylomicron secretion and prevents postprandial triglyceride elevation in humans. Journal of Clinical Lipidology. Volume 7, Issue 3, May-June 2013, Page 285.
Additional Infomation	Pradigastat has been used in trials studying the treatment of Non-alcoholic Fatty Liver Disease (NAFLD). Drug Indication Treatment of familial chylomicronaemia syndrome (type I hyperlipoproteinaemia

Solubility Data

Solubility (In Vitro)

DMSO : ~62.5 mg/mL (~137.22 mM) H2O : < 0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.49 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: 2.5 mg/mL (5.49 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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 3: 2.5 mg/mL (5.49 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1955 mL	10.9777 mL	21.9553 mL
	5 mM	0.4391 mL	2.1955 mL	4.3911 mL
	10 mM	0.2196 mL	1.0978 mL	2.1955 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.