4gb9

Publication Abstract from PubMed

Inhibition of PI3Kdelta is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3Kdelta. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3Kdelta inhibitors. Instead, the selectivity of the compounds for inhibition of PI3Kdelta relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3Kdelta binding pocket. The pharmacokinetic properties and the ability of compound 5 to inhibit the function of B-cells in vivo are described.

Potent and Highly Selective Benzimidazole Inhibitors of PI3-Kinase Delta.,Murray JM, Sweeney Z, Chan B, Balazs M, Bradley E, Castanedo G, Chabot C, Chantry D, Flagella M, Goldstein DM, Kondru RK, Lesnick J, Li J, Lucas MC, Nonomiya J, Pang J, Price S, Salphati L, Safina B, Savy P, Seward E, Ultsch M, Sutherlin D J Med Chem. 2012 Aug 9. PMID:22877085^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.