Cancer

In vitro and mouse studies identified a chromenecarbaldehyde-based IRE1 inhibitor that could help treat prostate cancer. Optimization and in vitro binding assays of a family of tool compound IRE1 inhibitors yielded a chromenecarbaldehyde-based compound that inhibited human IRE1 with an IC₅₀ of 290 nM. In four human prostate cancer cell lines, the compound decreased growth compared with vehicle. In one of the lines, the compound in combination with the prostate cancer drugs Zytiga abiraterone acetate, Xtandi enzalutamide, Jevtana cabazitaxel, paclitaxel or docetaxel decreased growth compared with any agent alone. In four xenograft mouse models of prostate cancer, the compound decreased tumor growth compared with vehicle. In one of the models, the compound in combination with Zytiga, Xtandi or Jevtana decreased tumor growth compared with any agent alone. Next steps could include testing the IRE1 inhibitor alone or in combination with the prostate cancer drugs in patient-derived xenograft (PDX) mouse models.

Pfizer Inc. and Astellas Pharma Inc. market the androgen receptor antagonist Xtandi for prostate cancer...