Discovery of a Novel Potent and Selective Calcium Release-Activated Calcium Channel Inhibitor: 2,6-Difluoro--(2'-methyl-3'-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-[1,1'-biphenyl]-4-yl)benzamide. Structure-Activity Relationship and Preclinical Characterization.

The role of calcium release-activated calcium (CRAC) channels is well characterized and is of particular importance in T-cell function. CRAC channels are involved in the pathogenesis of several autoimmune diseases, making it an attractive therapeutic target for treating inflammatory diseases, like rheumatoid arthritis (RA). A systematic structure-activity relationship study with the goal of optimizing lipophilicity successfully yielded two lead compounds, and .

Predicting toxicities in humans by nonclinical safety testing: an update with particular reference to anticancer compounds.

The sensitivity of the various preclinical models used to predict toxicity in humans varies. In this review, we analyze the various models used to predict safety in drug discovery and development with a view to understanding their translational value in humans. Twenty recently approved anticancer drugs were studied and the available nonclinical and clinical adverse effects information available from the US Food and Drug Administration (FDA) was analyzed.