Troponin Activator, CK-2017357

An orally bioavailable, non-toxic imidazopyrazinol compound that directly and selectively binds to the troponin complex in fast skeletal muscle (K_d = 40 nM) and sensitizes it to calcium. Its binding site is believed to be between two or more troponin subunits. Exhibits very modest affinity for slow skeletal muscle troponin (K_d = 3.8 µM) and has no measurable affinity for cardiac muscle troponin. Effectively stimulates myosin ATPase activity in fast skeletal muscle (EC₅₀ = 390 nM), but has significantly reduced effect on mixed fiber type (EC₅₀ = 770 nM in bovine rectus abdominis muscle). Slows the first order rate constant for Ca²⁺ release by about 70% (from 14.7 s^-1 to 4.0 s^-1) and shifts the plot of myosin ATPase relationship to calcium leftwards in fast skeletal muscles without increasing the maximum recorded force or the shape of the curve. Shown to improve muscle function in a rodent model of neuromuscular disease where neural input is diminished.

An orally bioavailable, non-toxic imidazopyrazinol compound that directly and selectively binds to the troponin complex in fast skeletal muscle (K_d = 40 nM) and sensitizes it to calcium. Its binding site is believed to be between two or more troponin subunits. Exhibits very modest affinity for slow skeletal muscle troponin (K_d = 3.8 µM) and has no measurable affinity for cardiac muscle troponin. Effectively stimulates myosin ATPase activity in fast skeletal muscle (EC₅₀ = 390 nM), but has significantly reduced effect on mixed fiber type (EC₅₀ = 770 nM in bovine rectus abdominis muscle). Slows the first order rate constant for Ca²⁺ release by about 70% (from 14.7 s^-1 to 4.0 s^-1) and shifts the plot of myosin ATPase relationship to calcium leftwards in fast skeletal muscles without increasing the maximum recorded force or the shape of the curve. Shown to improve muscle function in a rodent model of neuromuscular disease where neural input is diminished.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Cell permeable: yes

Primary Target
troponin complex

Reversible: yes

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C).

Gordon, P., et al. 2013. Expert Opin. Phamacother.14, 1907.
Miciak, J.J., et al. 2013. Muscle Nerve.48, 279.
Russell, A.J., et al. 2012. Nat. Med.18, 452.

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