HP567

HP567 is a highly potent, brain-penetrating, and mutant-selective small molecule inhibitor of phosphoinositide 3-kinase alpha (PI3Kα) harboring the H1047R mutation. Developed by Hinova Pharmaceuticals, HP567 is designed to selectively target the PI3Kα H1047R mutant over wild-type PI3Kα (14-fold selectivity) and other PI3K isoforms (80-fold selectivity). This selectivity aims to avoid the on-target toxicities associated with wild-type PI3Kα inhibition, such as hyperglycemia and rash, which limit the clinical utility of non-selective inhibitors like alpelisib. In preclinical models, HP567 has demonstrated strong anti-tumor activity against H1047R-mutant breast, ovarian, and tongue squamous cell cancers, including brain-metastatic breast cancer models, without causing hyperglycemia or elevating plasma insulin levels.