产品说明书

Pradigastat

Print
Chemical Structure| 956136-95-1 同义名 : LCQ-908
CAS号 : 956136-95-1
货号 : A281007
分子式 : C25H24F3N3O2
纯度 : 98%+
分子量 : 455.472
MDL号 : MFCD25562905
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 60 mg/mL(131.73 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 LCQ-908 is a potent and oral active diacylglycerol acyltransferase 1 (DGAT1) inhibitor, used as anti-obesity and anti-diabetic agents. DGAT-1 is recognized to catalyze the conversion of diacylglycerol and fatty acyl CoA to triacylglycerol, which is highly expressed in the small intestine and plays a key role in postprandial triglyceride synthesis. LCQ908 inhibited BCRP-mediated efflux activity in a dose-dependent fashion in a BCRP over-expressing human ovarian cancer cell line with an IC50 value of 5 μM[3]. LCQ908 inhibited OATP1B1, OATP1B3 (estradiol 17β glucuronide transport), and OAT3 (estrone 3 sulfate transport) activity in a concentration-dependent manner with estimated IC50 values of 1.66 ± 0.95 μM, 3.34 ± 0.64 μM, and 0.973 ± 0.11 μM, respectively[3]. LCQ908 was fond to suppress the postprandial triglyceride levels in rats, dogs as well as monkeys. LCQ908 decreased the postprandial rate of CM-TG secretion into the lymphatic duct and reduced the size of CMs[1]. In a clinical trial, LCQ908 was absorbed slowly, with a median tmax of ∼10 hours and eliminated slowly with a long half-life[4]. LCQ908 treatment led to dose-dependent suppression of postprandial triglyceride excursions over 9 hours following a high-fat meal test. In addition, LCQ908 suppressed postprandial glucose and insulin and increased plasma glucagon-like peptide-1 levels[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.20mL

0.44mL

0.22mL

10.98mL

2.20mL

1.10mL

21.96mL

4.39mL

2.20mL
参考文献

[1]Jian Z, Ray T, et al. Proton exchange reactions in isotope chemistry (II) synthesis of stable isotope-labeled LCQ908. J Labelled Comp Radiopharm. 2014 Oct;57(12):670-3.

[2]Bauer D, Soon RL, et al. The DGAT1 inhibitor pradigastat does not induce photosensitivity in healthy human subjects: a randomized controlled trial using three defined sunlight exposure conditions. Photochem Photobiol Sci. 2016 Aug 31;15(9):1155-1162.

[3]Kulmatycki K, Hanna I, Meyers D, Salunke A, Movva A, Majumdar T, Natrillo A, Vapurcuyan A, Rebello S, Sunkara G, Chen J. Evaluation of a potential transporter-mediated drug interaction between rosuvastatin and pradigastat, a novel DGAT-1 inhibitor. Int J Clin Pharmacol Ther. 2015 May;53(5):345-55. doi: 10.5414/CP202275. PMID: 25740267.

[4]Meyers CD, Amer A, Majumdar T, Chen J. Pharmacokinetics, pharmacodynamics, safety, and tolerability of pradigastat, a novel diacylglycerol acyltransferase 1 inhibitor in overweight or obese, but otherwise healthy human subjects. J Clin Pharmacol. 2015 Sep;55(9):1031-41. doi: 10.1002/jcph.509. Epub 2015 May 27. PMID: 25854859.