BioCentury
ARTICLE | Distillery Therapeutics

Cancer

January 31, 2017 10:54 PM UTC

In vitro, cell culture and mouse studies identified a Zydelig idelalisib-based dual inhibitor of PI3Kβ and PI3Kδ that could help treat PTEN-deficient cancer. Chemical synthesis and testing in enzymatic activity assays of Zydelig analogs yielded a compound that inhibited PI3Kβ and PI3Kδ with IC50 values of 7.8 and 5.3, respectively. In human prostate and breast cancer cell lines harboring loss-of-function PTEN mutations and a human kidney cancer cell line harboring an activating PI3Kβ mutation, the compound inhibited cell viability with IC50 values of 3.4-7.3 nM and pan-PI3K activity with IC50 values of 2-120 nM. In a xenograft mouse model of PTEN-deficient prostate cancer, the compound decreased pan-PI3K activity and tumor growth compared with vehicle. Next steps by Gilead Sciences Inc. could include testing the compound in additional PTEN-deficient cancer models...