BackgroundAMP-activated protein kinases (AMPK) are a family of protein kinases that are directly activated in response to increased cellular levels of AMP and are thus able to act as a sensor for lowered cellular energy levels. In response to low cellular energy levels, the activation of AMPK causes an increase in cellular levels of ATP by increasing metabolism of glucose and fatty acids.
Activation of AMPK is of clinical importance, as metformin, a biguanide drug (used to treat type II diabetes), exerts its main therapeutic effect by activating AMPK in the liver. However, this is through an indirect mechanism and does not occur in other tissues (probably because metformin is not readily taken up in other cell types). In experimental studies, the cell-permeable drug AICAR-riboside has been used to activate AMPK. AICAR-riboside is readily taken up and metabolised to ZMP, which in turn can activate AMPK. However, ZMP also activates a range of other AMP-activated enzymes, including glycogen phosphorylase and fructose 1:6 bisphosphatase. A-769662 is a cell permeable drug, that potently activates AMPK in cells (EC50 120 nM) and, unlike AICAR-riboside , does not activate other AMP target enzymes [1, 2]. When tested against a panel of 76 protein kinases, A-769662 was observed to only significantly inhibit the activity of PIM1 and PIM3 (>50% inhibition).
References
1 Cool, B., Zinker, B., Chiou, W., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A., Gagne, G., Iyengar, R., Zhao, G., Marsh, K., Kym, P., Jung, P., Camp, H. S. and Frevert, E. (2006) Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome.Cell Metab 3, 403-16
2 Sanders, M. J., Ali, Z. S., Hegarty, B. D., Heath, R., Snowden, M. A. and Carling, D. (2007) Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family.J Biol Chem 282, 32539-48
新西兰Symansis公司是新西兰一家发展抗体作为新药开发中细胞讯息传递研究工具的公司。
Symansis公司新推出Multi-Kinase ELISA Arrays试剂盒,采用特异的抗磷酸化激酶抗体和ELISA反应原理,使磷酸化激酶的检测变得简单。一次操作,可同时检测多个磷酸化激酶,避免了传统的Western blot方法需要分开操作及其一系列复杂繁琐的操作和等待。其酶抑制剂产品如下:
AKT AKt-I-1 SY AKT-I-1
AMPK A-769662 SY-A-769662
AUR (CDK) JNJ7706621 SY- JNJ7706621
Aurora VX-680 SY- VX-680
Bcl-2 ABT-737 SY- ABT-737
BCR-ABL Imatinib mesylate SY- Imatinib mesylate
BCR-ABL PD173955 SY-PD173955
CDK AT-7519 SY- AT-7519
CDK SNS-032 SY- SNS-032
EGFR Gefitinib SY- Gefitinib
EGFR Erlotinib SY- Erlotinib