molecules of the month

The AbbVie BCL-2 inhibitor prodrug (ABBV-167) is a phosphate prodrug of venetoclax used for treatment of chronic lymphocytic leukemia (CLL). This molecule has an interesting prodrug mechanism, masking an azaindole heterocycle through heterocycle N-alkylation. By improving the solubility, the dose needed of this prodrug relative to parent was greatly reduced, nicely illustrated with pill pictures in the manuscript. A clinical study on healthy volunteers revealed that both solid and liquid dosage forms of ABBV-167 significantly improve the bioavailability of venetoclax under fasted conditions and reduce the food effect with respect to venetoclax.