TY-2291

TY-2291 is an orally active, allosteric, and mutant-selective phosphoinositide 3-kinase alpha (PI3Kα) inhibitor developed by TYK Medicines. It is designed to selectively target mutant forms of PI3Kα (such as those with helical domain mutations E542K and E545K, or kinase domain mutations H1047R/L) while sparing wild-type (WT) PI3Kα. By avoiding WT PI3Kα inhibition, which is critical for cellular glucose homeostasis, TY-2291 aims to mitigate dose-limiting toxicities like hyperglycemia and hyperinsulinemia that are commonly associated with approved orthosteric PI3Kα inhibitors. In preclinical studies, TY-2291 has demonstrated potent antiproliferative activity against multiple PI3Kα-mutant cancer cell lines and robust tumor-inhibitory efficacy in mouse models, with no adverse effects on fasting plasma glucose levels.