Discovery of Potent, Selective, and Orally Available IRE1 alpha Inhibitors

Inositol-requiring enzyme 1α (IRE1α) is a sensor protein that plays a key role in multiple myeloma (MM) and is a potential therapeutic target for this type of blood cancer. IRE1α is activated by ER stress, which is common in MM cells due to their high protein synthesis.

WuXi AppTec recently contributed to a study which identified a potent and selective IRE1α inhibitor, designated G-5758, that was well tolerated following multiday oral administration. Significantly, G-5758 demonstrated comparable pharmacodynamic effects to induced IRE1 knockdown in a KMS-11 multiple myeloma model.