QLS1522

QLS1522 is a potent and mutant-selective allosteric inhibitor of Phosphoinositide 3-kinase alpha (PI3Kα), specifically targeting PIK3CA mutations such as H1047R (kinase domain) and helical domain mutations. Developed by Qilu Pharmaceutical, it is designed to spare wild-type PI3Kα, thereby reducing the on-target metabolic toxicities, such as hyperglycemia and hyperinsulinemia, typically associated with non-selective PI3Kα inhibitors like alpelisib. Preclinical data presented at AACR 2026 indicates that QLS1522 maintains high selectivity over other PI3K isoforms (β, γ, δ) and demonstrates robust anti-tumor activity in ER-positive breast cancer models. The compound exhibits a favorable pharmacokinetic profile and a wide therapeutic window, with IND-enabling studies currently underway to support its clinical development for PIK3CA-mutant solid tumors.