Ki = 300 nM
ML-7 is a myosin light chain kinase inhibitor.
Great attention has been gained to the role of myosin light chain kinase (MLCK) pathway in the development of cardiovascular disease and I/R injury. MLCK pathway has been reported to be involved in the pathology of cardiovascular disorders, and the MLCK inhibition could protect heart from I/R injury by regulation of phosphorylation of MLC.
In vitro: Rats with myocardial infarction were intravenously infused with rhNRG-1. The cMLCK expression and phosphorylated MLC-2v were up-regulated in rat treated with rhNRG-1 significantly. Moreover, the restoration of rhNRG-1-induced sarcomeric organization in serum-free cultured neonatal rat cardiomyocytes with rhNRG-1 was inhibited by ML-7 [1].
In vivo: Administration of ML-7 from 10 min before ischemia to the first 10 min of reperfusion led to a significant recovery of heart contractility. Gel analyses of two-dimensional electrophoresis revealed eight proteins with decreased levels in I/R hearts. Six proteins involved in energy metabolism, which were cytochrome b-c1 complex subunit 1, ATP synthase beta subunit, cytochrome c oxidase subunit, mitochondrial NADHdehydrogenase, NADHdehydrogenase iron-sulfur protein 8, and succinyl-CoA ligase subunit. The other two protein levels decreased in I/R hearts, which were peroxiredoxin-2 and tubulin. In addition, ML-7 treatment increased the level of succinyl-CoA ligase, which was a key enzyme involved in the citric acid cycle [2].
Clinical trial: N/A
References:
[1] Gu X,Liu X,Xu D,Li X,Yan M,Qi Y,Yan W,Wang W,Pan J,Xu Y,Xi B,Cheng L,Jia J,Wang K,Ge J,Zhou M. Cardiac functional improvement in rats with myocardial infarction by up-regulating cardiac myosin light chain kinase with neuregulin. Cardiovasc Res.2010 Nov 1;88(2):334-43.
[2] Lin HB,Cadete VJ,Sawicka J,Wozniak M,Sawicki G. Effect of the myosin light chain kinase inhibitor ML-7 on the proteome of hearts subjected to ischemia-reperfusion injury. J Proteomics.2012 Sep 18;75(17):5386-95.
