Figure 5.

Concentration-dependent response of mavacamten (MYK-461) in purified human actomyosin systems. A, human cardiac myosin-S1 (0.25 μm) and all mutants were assayed with a constant concentration of actin (14 μm) at varying concentrations of mavacamten. B, an expanded panel, showing the subtle differences in the potency of mavacamten against all mutant myosins assayed. ATPase rates were normalized to DMSO controls for each myosin type assayed, and EC₅₀ values were calculated using a four-parameter-fit model in Prism (GraphPad). DMSO controls rates of 0.269 ± 0.002 μm/s, 0.142 ± 0.001 μm/s, 0.138 ± 0.002 μm/s, 0.184 ± 0.001 μm/s, 0.135 ± 0.001 μm/s, and 0.078 ± 0.001 μm/s were measured for wild-type, R403Q, R453C, R719W, R723G, and G741R human cardiac myosin-S1, respectively.