Picking a PCSK9

As the first mAbs against PCSK9 are making their market debuts, several companies are vying to replace them with oral candidates. Liphorus Pharmaceuticals Inc. has assembled a test kitchen of screens for small molecules with different PCSK9-targeting mechanisms - including one mechanism that stymied other companies.

PCSK9 binds to and enhances the degradation of LDL receptors, which are responsible for clearing LDL from the circulation. PCSK9 must cleave itself to exit the endoplasmic reticulum and leave the cell, where it circulates and binds to the LDL receptor to target it for lysosomal degradation...