A first-in-class Wiskott-Aldrich syndrome protein activator with antitumor activity in hematologic cancers.

Hematologic cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies are needed.

Mapping, Structure and Modulation of PPI.

Because of the key relevance of protein-protein interactions (PPI) in diseases, the modulation of protein-protein complexes is of relevant clinical significance. The successful design of binding compounds modulating PPI requires a detailed knowledge of the involved protein-protein system at molecular level, and investigation of the structural motifs that drive the association of the proteins at the recognition interface. These elements represent hot spots of the protein binding free energy, define the complex lifetime and possible modulation strategies.

Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models.

Copanlisib is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor with preferred activity toward PI3Kα and PI3Kδ. Despite the clear overall clinical benefit, the number of patients achieving complete remissions with the single agent is relatively low, a problem shared by the vast majority of targeted agents. Here, we searched for novel copanlisib-based combinations.