A 922500 (DGAT-1 Inhibitor 4a) is a potent, selective, and orally bioavailablediacylglycerolacyltransferase1 (DGAT-1)inhibitor withIC₅₀s of 9 and 22 nM against human and mouse DGAT-1, respectively.

IC50: 9 nM (human DGAT-1), 22 nM (mouse DGAT-1)^[1]

A 922500 (A-922500) demonstrates excellent selectivity over other acyltransferases, including DGAT-2 (IC₅₀=53 μM) and the phylogenetic family members acyl coenzyme A cholesterol acyltransferase-1 and -2 (IC₅₀=296 μM)^[1].

DGAT-1 inhibitor A 922500 (A-922500) reduces serum triglyceride levels from baseline at all doses tested; however, this is only statistically significant at the 3 mg/kg dose, which lowers serum triglycerides by 53%. Similarly, the 3 mg/kg dose of A 922500 significantly reduces serum FFA concentrations by 55% and total cholesterol by 25%. DGAT-1 inhibition has no significant effect on body weight at any dose tested. Although A 922500 dpes not significantly affect LDL-cholesterol or HDL-cholesterol individually, the serum LDL/HDL-cholesterol ratio is significantly improved by A 922500 at 0.3 and 3 mg/kg. Similar to the dyslipidemic hamster, treatment with 3 mg/kg A 922500 significantly reduces serum triglyceride concentrations (39%). FFA levels significantly increase over the 14-day period in vehicle-treated animals. This increase is inhibited in a dose-dependent manner by A 922500 such that FFA concentrations are 32% lower after 14 days of treatment with the DGAT-1 inhibitor at 3 mg/kg, compared with the vehicle group (p< 0.05). HDL-cholesterol is significantly increased from baseline levels by A 922500 at 0.3 and 3 mg/kg; however, this is only significantly increased compared with vehicle at the 3 mg/kg dose. Body weight significantly increases over the 2-week period in vehicle-treated rats, and this is not affected by A 922500. LDL-cholesterol is significantly reduced in the vehicle treated group. DGAT-1 inhibition does not further reduce LDL-cholesterol and has no effect on total cholesterol^[1].

428.48

Solid

C₂₆H₂₄N₂O₄

959122-11-3

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 50 mg/mL(116.69 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (5.83 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.83 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液