Publications by authors named "Paul M Blaney"
Bioorg Med Chem Lett
July 2012
Article Synopsis
- - A new inhibitor of the PI3Kδ enzyme is introduced, showing over 200 times more selectivity for other PI3K isoforms and additional kinases.
- - The selectivity is explained using structure-activity relationships and detailed crystal structures of the inhibitor bound to a specific mutant form of PI3Kγ.
- - Pharmacokinetic studies in rats and mice indicate that this inhibitor could be a valuable tool for in vivo research.
Article Synopsis
- PI3Kδ is a lipid kinase found mostly in leukocytes and plays a crucial role in B cell signaling, making it a target for treating diseases like rheumatoid arthritis.
- Researchers discovered new, effective PI3Kδ inhibitors and developed a structural understanding that supports their ability to selectively inhibit different PI3K isoforms (α, β, γ).
- The study highlighted a key element in their design that relates to CYP3A4 time-dependent inhibition, and various strategies were suggested to monitor and reduce this inhibitor issue, utilizing structure-based design for further improvements.
