BioCentury
ARTICLE | Distillery Therapeutics

Cancer

September 20, 2017 6:58 PM UTC

In vitro, cell-based and mouse studies identified an aminoanilide-based dual NamPRT/HDAC1 inhibitor that could help treat colorectal cancer. Chemical synthesis and in vitro testing of ortho-aminoanilide analogs in enzymatic activity assays yielded a compound that inhibited NamPRT and HDAC1 with IC50 values of 31 and 55 nM, respectively. In a colorectal cancer cell line, the compound increased apoptosis and levels of autophagy markers compared with vehicle. In a xenograft mouse model of colorectal cancer, the compound decreased tumor growth compared with a NamPRT inhibitor tool compound or the HDAC inhibitor Zolinza vorinostat. Next steps include optimization of the dual inhibitor...