F90927: A New Member in the Class of Cardioactive Steroids

Abstract

F90927 is a newly developed cardioactive drug with a steroid-like structure. It acts directly and agonistically on the cardiac L-type Ca 2+ channel by shifting its voltagedependent activation toward more negative potentials. This leads to an increased influx of Ca 2+ and, therefore, to a stronger contraction; however, no arrhythmias occur. Calcium current stimulation can already be observed at nanomolar concentrations, but higher concentrations of F90927 elevate intracellular Ca 2+ concentration, causing a reduction of the myocardial compliance and an increased diastolic blood pressure. Vessels also react to F90927 and contract in its presence. Binding of F90927 with the L-type Ca 2+ channel presumably occurs in the vicinity of the transmembrane domains III and IV of the α 1 subunit. F90927 exhibits no use dependence and interacts with Ca 2+ channel inhibitors of all three known classes of channel modulators (dihydropyridines, phenylalkylamines, and benzothiazepines), suggesting that it is a member of a new class of Ca 2+ channel modulators. Due to its adverse effects on blood pressure and vessel contraction, F90927 is not an ideal drug candidate. It has, however, some unique properties, which makes it a promising tool to study the function of the L-type Ca 2+ channel.

UNBS1450 from Calotropis procera as a regulator of signaling pathways involved in proliferation and cell death

“…With varying Kd values, the inhibition complexes are probably internalized and degraded. Inhibitors of the Na + ,K + transporter lead to an increase of the cytosolic Na + concentration and are thus influencing the thermodynamics of the Na + ,Ca 2+ exchange pump finally resulting in an increased Ca 2+ concentration in sarcoplasmic reticulum[54] (Na + -Lag hypothesis).However, recent studies suggest that this Na + pump inhibition is not necessary to obtain an inotropic effect on myocytes[55]. By interacting with cardiac glycosides, the Na + -K + pump complex has been shown to act as a signalosome.…”