pan-mutant selective PI3Kα inhibitor / TYK Medicines - LARVOL DELTA

Identification and characterization of pan-mutant selective PI3Kα inhibitors with the capability of PI3Kα H1047R protein degradation (AACR 2026) - P3 | "Orthosteric inhibitors of PI3Kα, such as alpelisib and inavolisib, have been approved for the treatment of patients with advanced HR+/HER2− breast cancer... Several allosteric and potent pan-mutant PI3Kα inhibitors developed by TYK Medicines exhibited high selectivity over wild-type (WT) PI3Kα. Our observations revealed that the compounds inhibited AKT phosphorylation in the T47D (PI3Kα H1047R) cell line with an IC50 in the single-digit nanomolar range, demonstrating nearly 200 times more selectivity compared to SK-BR-3 (PI3Kα WT) cells at same time. In in vitro antiproliferative assays, the compounds displayed superior antiproliferative activity against various PI3Kα mutant cells, including T47D, HCC1954 (PI3Kα H1047R), and MCF7 (PI3Kα E545K), compared to STX-478 and RLY-2608."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

TYK Medicines…is pleased to announce that the research progress and results for five innovative drug projects under development of the Company, namely TY-0609 (CDK4 inhibitor), TY-2699a (CDK7 inhibitor), TY-2719 (EGFR/FAK (PROTAC) inhibitor), PI3Kα (PI3Kα inhibitor), and TY-1054 (YAP-TEAD inhibitor), will be presented by the Company in poster presentation at 2026…AACR annual meeting (HKEXnews)

Preclinical • Solid Tumor