Discovery of a Novel Inhaled PI3Kδ Inhibitor for the Treatment of Respiratory Diseases.

Oral PI3Kδ inhibitors such as Idelalisib and Duvelisib have shown efficacy as anticancer agents and Idelalisib has been approved for the treatment of three B-cell cancers. However, Idelalisib has a black box warning on its product label regarding the risks of fatal and serious toxicities including hepatic toxicity, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation. Some of these side effects are mechanism-related and could hinder the development of Idelalisib for less severe conditions.

Structure-activity relationship of kahalalide F synthetic analogues.

Kahalalide F (KF) is a natural product currently under phase II clinical trials. Here, we report the solid phase synthesis of 132 novel analogues of kahalalide F and their in vitro activity on a panel of up to 14 cancer cell lines. The structure-activity relationship of these analogues revealed that KF is highly sensitive to backbone stereotopical modification but not to side chain size modification.