MLCK Inhibitor

Ulacamten (CK-4021586; CK-586) is an orally active cardiac myosin inhibitor and an inhibitor of the double-headed cardiac heavy meromyosin (HMM)ATPase (excluding single-headed myosin subfragment-1), with an EC₅₀ of 2.9 μM. Ulacamten regulates cardiac myosin, reduces excessive myocardial contractility, and alleviates left ventricular outflow tract obstruction. Ulacamten increases the left ventricular short-axis systolic internal diameter, inhibits dobutamine-induced exacerbation of obstruction, and exerts only a mild reducing effect on left ventricular systolic function. Ulacamten also inhibits the fractional shortening of the short axis without altering calcium transients. Ulacamten shows good safety and tolerability in purpose-bred cats with naturally occurring obstructive hypertrophic cardiomyopathy.

MS-347a is an inhibitor of myosin light chain kinase (MLCK) and protein kinase C (PKC), with IC₅₀ values of 9.2 μM, 31 μM and 16 μM against calmodulin-dependent MLCK, calmodulin-independent MLCK and PKC, respectively. MS-347a binds to the catalytic domain of MLCK and blocks both calmodulin-dependent and calmodulin-independent MLCK activity. MS-347a inhibits the growth of drug-sensitive fission yeast and multiple ascomycete phytopathogenic fungi. MS-347a exhibits fungicidal activity against a variety of phytopathogenic fungi and protective activity against Magnaporthe oryzae in rice seedlings. MS-347a shows antibacterial activity against specific Gram-positive bacteria and Proteus vulgaris. MS-347a can be used in studies related to rice blast, bacterial infections and phytopathogenic fungal diseases.

ME-3407 (EF-4040) is a H⁺-K⁺-ATPase redistribution disruptor and myosin light chain kinase (MLCK) and protein kinase A inhibitor. ME-3407 blocks gastric acid secretion and aminopyrine accumulation by inhibiting microsomal-to-apical membrane redistribution of H⁺-K⁺-ATPase and suppressing MLCK-mediated myosin light chain phosphorylation. ME-3407 is promising for research of peptic ulcer.