A922500

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

A922500 是人和小鼠 DGAT-1 的抑制剂，IC50 分别为 7 nM 和 24 nM，相对于相关酰基转移酶、hERG 和一组抗靶标具有良好的选择性。

A-922500 is a potent orally active inhibitor of DGAT-1 activity, inhibiting both human and mouse forms of the enzymes with IC50 values of 7 and 24 nM, respectively. Acyl CoA/diacylglycerol acyltransferase (DGAT) 1 is one of two known DGAT enzymes that catalyze the final and only committed step in triglyceride biosynthesis.

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) .

DGAT-1 inhibitorA 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.

A-922500 | A 922500 | A922500

Apoptosis

NF-κB

human DGAT-1 , mouse DGAT-1 , DGAT-2

Metabolic Disease

——

959122-11-3

428.48

C26H24N2O4

>98% (HPLC)

DMSO : ≥ 50 mg/mL; 116.69 mM

OC(=O)[C@@H]1CCC[C@H]1C(=O)C1=CC=C(C=C1)C1=CC=C(NC(=O)NC2=CC=CC=C2)C=C1

(1R,2R)-2-(4'-(3-phenylureido)-[1,1'-biphenyl]-4-carbonyl)cyclopentane-1-carboxylic acid

(-20℃)

With Ice Pack

≥ 2 years