Cell lines

Primary neonatal cardiomyocytes

Preparation method

Soluble in DMSO >15.95mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10 μM, 24h

Applications

The restoration of rhNRG-1(Recombinant human neuregulin-1)-induced sarcomeric organization in serum-free cultured neonatal rat cardiomyocytes with rhNRG-1 was inhibited by ML-7. RhNRG-1 could improve cardiac function in experimental heart failure models.

Animal models

two-month-old male New Zealand white rabbits

Dosage form

1 mg/kg/day, 12 weeks, oral administration

Application

ML7 might ameliorate VED(Vascular endothelial dysfunction) and AS(atherosclerosis) by regulating the TJ(tight junction) proteins ZO1(zona occludens) and occludin in a rabbit model of atherosclerosis via mechanisms involving MLCK(myosin light chain kinase) and MLC phosphorylation.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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.