ws-691

WS-691 is a highly Potent and Orally Active ABCB1 Modulator. WS-691 significantly increased sensitization of ABCB1-overexpressed SW620/Ad300 cells to paclitaxel (PTX) (IC50 = 22.02 nM). WS-691 significantly increased the intracellular concentration of PTX and [3H]-PTX while decreasing the efflux of [3H]- PTX in SW620/Ad300 cells by inhibiting the efflux function of ABCB1. WS-691 could stabilize ABCB1 by directly binding to ABCB1 WS-691 increased the sensitivity of SW620/Ad300 cells to PTX in vivo without observed toxicity.

Istaroxime, also known as PST-2744, is a positive inotropic agent that mediates its action through inhibition of sodium/potassium adenosine triphosphatase (Na+/K+ ATPase). Na+/K+ ATPase inhibition increases intracellular sodium levels, which reverses the driving force of the sodium/calcium exchanger, inhibiting calcium extrusion and possibly facilitating calcium entry. Additionally, Istaroxime increases intracellular calcium by improving the efficacy by which intracellular calcium triggers sarcoplasmic reticulum calcium release, and by accelerating the inactivation state of L-type calcium channels, which allow for calcium influx.