ronacaleret and Osteoporosis

Daily subcutaneous self-injection and weekly subcutaneous injection formulas of teriparatide are available as anabolic agents in Japan. These injection formulas are expected to serve as a new treatment choice for high fracture-risk patients with osteoporosis. In addition, studies using new anabolic agents such as PTHrP, calcilytics, and Wnt inhibitor antagonists/antibodies are under way to develop new anabolic agents. These agents may become new treatment drugs for osteoporotic patients especially with low bone turnover.

Topics: Adaptor Proteins, Signal Transducing; Anabolic Agents; Animals; Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Bone Morphogenetic Proteins; Genetic Markers; Humans; Indans; Injections, Subcutaneous; Osteoporosis; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Phenylpropionates; Receptors, Calcium-Sensing; Teriparatide; Wnt Signaling Pathway

The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis.

Topics: Administration, Oral; Allosteric Regulation; Anabolic Agents; Animals; Cell Line; Cyclopropanes; Drug Discovery; Humans; Indans; Microsomes, Liver; Osteoporosis; Phenylpropionates; Rats; Receptors, Calcium-Sensing