In a recent study published in Science, Liu and colleagues used computational ultra-large library docking to discover new chemotypes acting as positive allosteric modulators (PAM) of the Calcium-Sensing Receptor (CaSR),¹ which bind the receptor with very high affinity and shows evidence of biased signaling, i.e. the preferential activation of one signaling pathway over others, compared to the receptor’s natural ligands. Importantly, the in vivo test of one substance (‘54159) did not induce hypocalcemia, which is an advantage over FDA-approved calcimimetics, which are limited in clinical practice due to their potential to disrupt calcium homeostasis and cause hypocalcemia.

在最近发表在《科学》杂志上的一项研究中，Liu 及其同事使用计算超大型文库对接发现了作为钙感应受体 （CaSR） 的正变构调节剂 （PAM） 的新化学型，¹ 它们以非常高的亲和力结合受体，并显示出偏向信号的证据，即与受体的天然配体相比，一种信号通路优先激活其他信号通路。重要的是，一种物质 （'54159） 的体内测试不会诱导低钙血症，这比 FDA 批准的拟钙药更具优势，后者由于可能破坏钙稳态并导致低钙血症，在临床实践中受到限制。