Synthesis of improved lysomotropic autophagy inhibitors.

Autophagy is a conserved cellular pathway used to recycle nutrients through lysosomal breakdown basally and under times of stress (e.g., nutrient deprivation, chemotherapeutic treatment).

Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents.

A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models.