Cancer
Cell culture and mouse studies suggest an N-carboxyaniline-based selective androgen receptor degrader (SARD) could help treat castration-resistant prostate cancer (CRPC). The SARD is a previously reported N-carboxy-cyanotrifluoromethylaniline analog that binds the ligand-binding domain of androgen receptor (Ki = 267 nM) and degrades the receptor. In three human androgen receptor antagonist-resistant CRPC cell lines, the SARD decreased proliferation compared with the androgen receptor antagonist Xtandi enzalutamide. In two xenograft mouse models of CRPC, the SARD decreased tumor growth and tumor levels of prostate-specific antigens compared with Xtandi. In a patient-derived xenograft (PDX) mouse model of metastatic CRPC expressing AR-V7 and another androgen receptor splice variant, the SARD decreased tumor volume compared with vehicle. Next steps by GTx Inc. include testing the compound in additional animal models of CRPC (see "Degrade and Destroy." BioCentury Innovations (May 7, 2015)).
GTx has the SARD in preclinical testing to treat prostate cancer...