CNX-012-570, a direct AMPK activator provides strong glycemic and lipid control along with significant reduction in body weight; studies from both diet-induced obese mice and db/db mice models.

Objectives: AMP activated protein kinase (AMPK) regulates the coordination of anabolic and catabolic processes and is an attractive therapeutic target for T2DM, obesity and metabolic syndrome. We report the anti-hyperglycemic and anti-hyperlipidemic effects of CNX-012-570 is an orally bioavailable small molecule (molecular weight of 530 Daltons) that directly activates AMPK in DIO and db/db animal models of diabetes.

Methods: Activity and efficacy of the compound was tested in cell based as well as cell free systems in vitro.

Length variations amongst protein domain superfamilies and consequences on structure and function.

Background: Related protein domains of a superfamily can be specified by proteins of diverse lengths. The structural and functional implications of indels in a domain scaffold have been examined.

Methodology: In this study, domain superfamilies with large length variations (more than 30% difference from average domain size, referred as 'length-deviant' superfamilies and 'length-rigid' domain superfamilies (<10% length difference from average domain size) were analyzed for the functional impact of such structural differences.

CUSP: an algorithm to distinguish structurally conserved and unconserved regions in protein domain alignments and its application in the study of large length variations.

Background: Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner.