ABSTRACT
Spin-orbit torque has attracted considerable attention as a means to overcome limits of devices based on spin-transfer torque. However, a small magnetic field that is collinear to the current flow must be applied to break symmetry and induce deterministic current-induced magnetization switching. Recently, a junction utilizing interlayer coupling mediated by a Ru spacer layer between two CoFe layers was designed for symmetry breaking and exhibited current-induced magnetization switching without a magnetic field. Here, we demonstrate zero-field current-induced switching of the perpendicular magnetization of a Co layer that is indirectly coupled with a CoFe layer via a Ta spacer. The weak interlayer coupling exhibited by Ta allows the layer thickness to be relatively small (≈0.5 nm), enabling appropriate interlayer coupling to induce spin-orbit torque for current-induced magnetic switching. External magnetic field effects on switching characteristics show that the current switching process is quite stable against external environments.
ABSTRACT
Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.
