Isoform selective phosphoinositide 3-kinase gamma and delta inhibitors and their therapeutic potential

Phosphoinositide 3-kinases (PI3Ks) represent a family of dual specificity kinases that by acting as both lipid and protein kinases regulate numerous biological processes, including cell growth, differentiation, survival, proliferation, migration and metabolism. The availability of genetically modified mice has recently allowed the functional characterization of class I PI3Ks, which are the most well studied PI3Ks. Whereas PI3Kalpha and PI3Kbeta are ubiquitously expressed, PI3Kdelta and PI3Kgamma are mainly restricted to leukocytes and represent key modulators of innate and adaptive immune responses. Therefore, PI3Kdelta and PI3Kgamma have become attractive drug targets for the treatment of disorders of both innate and adaptive immune system, causing inflammatory and allergic diseases. The lack of specificity, isoform selectivity and biopharmaceutical properties of the initially available pharmacological inhibitors have provided impetus to the development of novel compounds that, by exhibiting improved isoform selectivity, potency and pharmacokinetic profile, might be more safely employed. Here, we describe recently published patent specifications disclosing new PI3K inhibitors, with a main focus on compounds displaying some selectivity for PI3Kdelta and gamma isoforms and their potential therapeutic applications.