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AZD7545

现货
Catalog No.
B1286
有效的PDHK选择性抑制剂
组合的产品项目
规格价格库存 数量
25mg
¥ 5,230.00
现货
10mM (in 1mL DMSO)
¥ 2,350.00
现货
5mg
¥ 1,700.00
现货
10mg
¥ 2,800.00
现货
50mg
¥ 6,700.00
现货
100mg
¥ 10,300.00
现货

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Background

AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2) with IC50 value of 6.4nM [1].

PDH catalyzes the decarboxylation of pyruvate, converting it to acetyl-CoA. This enzyme is regulated by PDH kinases. The inhibitor of PDHK is developed for the treatment of type 2 diabetes. AZD7545 is a selective inhibitor of PDHK2. It inhibits PDHK1 and PDHK2 with IC50 values of 36.8nM and 6.4nM, respectively. Besides that, AZD7545 increases PDH activity with EC50 value of 5.2nM when using recombinant human PDHK2. In vivo studies show that administration of AZD7545 significantly activates PDH activity in liver and partially activates PDH activity in skeletal muscle and heart. In Zucker (fa/fa) rats, AZD7545 at dose of 10 mg/kg increases muscle PDH from 61% to 97% active and liver PDH from 33.5% to 72.8% [1, 2].

References:
[1] Morrell J A, Orme J, Butlin R J, et al. AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. Biochemical society transactions, 2003, 31(6): 1168-1170.
[2] Mayers R M, Butlin R J, Kilgour E, et al. AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats. Biochemical Society Transactions, 2003, 31(6): 1165-1167.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt478.87
Cas No.252017-04-2
FormulaC19H18ClF3N2O5S
Solubility≥21.85mg/mL in DMSO
Chemical Name4-[3-chloro-4-[[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino]phenyl]sulfonyl-N,N-dimethylbenzamide
SDFDownload SDF
Canonical SMILESCC(C(=O)NC1=C(C=C(C=C1)S(=O)(=O)C2=CC=C(C=C2)C(=O)N(C)C)Cl)(C(F)(F)F)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

PDHK同工酶抑制试验

[33P]ATP与PDH 亚基E1的结合测定实验于30℃条件下、含有100 μM ATP 和 E2亚基的Mops-K+缓冲液中进行。全部采用重组人蛋白。化合物J,K,L是AZD7545的衍生物。 IC50值以平均数±标准差的形式呈现,观测次数标注在括号中。

动物实验 [2]:

动物模型

Wistar大鼠模型; 肥胖的(fa/fa) Zucker大鼠模型

剂量

3、10、和30 mg/kg;每天两次口服给药;持续7天

应用

在Wistar大鼠模型中,AZD7545更加有效地增加肝脏的PDH活性,而增加骨骼肌和心脏的PDH活性较弱;同时,在肥胖的(fa/fa) Zucker大鼠模型中,AZD7545显著地提高体内丙酮酸脱氢酶活并且有效地控制血糖。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1. Morrell, J. A., Orme, J., Butlin, R. J., Roche, T. E., Mayers, R. M. and Kilgour, E. (2003) AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. Biochem Soc Trans. 31, 1168-1170

2. Mayers, R. M., Butlin, R. J., Kilgour, E., Leighton, B., Martin, D., Myatt, J., Orme, J. P. and Holloway, B. R. (2003) AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats. Biochem Soc Trans. 31, 1165-1167

生物活性

Description AZD7545是有效的PDHK抑制剂,对PDHK1和PDHK2的IC50值分别为36.8 nM和6.4 nM。
靶点 PDHK2 PDHK1        
IC50 6.4 nM 36.8 nM        

质量控制

化学结构

AZD7545