The natural product prodigiosin 1, often described as an H+/Cl- symport cotransporter, can transport Cl- across lipid vesicles via an anion exchange (or antiport) mechanism.

Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kβ/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kβ and δ isoforms in the treatment of a number of inflammatory diseases.

Self‐assembled transporter: Self‐association of a partial‐cone calixarene amide provides membrane‐active aggregates that enable the transport of chloride anions across phospholipid membranes (see picture). Additionally, a regulatory system is described, wherein an inactive calixarene analogue inhibits the active chloride transporter.

The development and optimization of a series of quinolinylpurines as potent and selective PI3Kδ kinase inhibitors with excellent physicochemical properties are described. This medicinal chemistry effort led to the identification of 1 (AMG319), a compound with an IC50 of 16 nM in a human whole blood assay (HWB), excellent selectivity over a large panel of protein kinases, and a high level of in vivo efficacy as measured by two rodent disease models of inflammation.

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