Discovery and Development of a Novel PI3K/HDAC Dual Inhibitor PH-20 for the Treatment of Lymphoma

Heng Xu, PhD, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College

Lymphoma is a cancer of the lymphatic system and often occurs in elderly patients. To address the limited therapeutic efficacies and potential drug-drug interactions derived from single-target anti-lymphoma drugs, a structurally distinct PI3K/HDAC dual inhibitor PH-20 was identified to bear nanomolar potencies against PI3K and HDAC at the same time. PH-20 displays high anti-proliferative activities on a variety of lymphoma cell lines, yielding a synergistic effect of combined inhibition of both PI3K and HDAC. It has been confirmed that PH-20 shows superior anti-cancer activities in lymphoma xenograft animal models as well as a favorable safety profile. Overall, PH-20 shows promise in discovery of new therapeutics for the treatment of lymphoma by simultaneously targeting PI3K and HDAC pathways with a single molecule.