UCL-TRO-1938

UCL-TRO-1938 (also known as 1938) is a first-in-class small-molecule allosteric activator of the phosphoinositide 3-kinase alpha (PI3Kα) isoform. Developed by researchers at University College London (UCL) and the Francis Crick Institute, it represents a novel therapeutic strategy in oncology by hyperactivating an oncogenic pathway beyond its survival fitness zone to trigger cell death. Mechanistically, 1938 induces PI3K activation-induced cell death (PI3K-AICD) by simultaneously stimulating anabolic PI3K/mTORC1 signaling in nutrient-deprived or hypoxic environments, leading to an unresolvable metabolic energy crisis and endoplasmic reticulum stress. This approach selectively targets cancer cells while sparing non-transformed cells, particularly in lung cancer models where it shows synergy with SCD1 inhibitors. Beyond oncology, the compound has been investigated for its potential in cardioprotection and neural regeneration.

Other names

1938