Article
Potent and selective inhibitors of PI3Kδ: obtaining isoform selectivity from the affinity pocket and tryptophan shelf.
Bioorganic & medicinal chemistry letters - 1 Jul 2012
Sutherlin Daniel P, Baker Stewart, Bisconte Angelina, Blaney Paul M, Brown Anthony, Chan Bryan K, Chantry David, Castanedo Georgette, DePledge Paul, Goldsmith Paul, Goldstein David M, Hancox Timothy, Kaur Jasmit, Knowles David, Kondru Rama, Lesnick John, Lucas Matthew C, Lewis Cristina, Murray Jeremy, Nadin Alan J, Nonomiya Jim, Pang Jodie, Pegg Neil, Price Steve, Reif Karin, Safina Brian S, Salphati Laurent, Staben Steven, Seward Eileen M, Shuttleworth Stephen, Sohal Sukhjit, Sweeney Zachary K, Ultsch Mark, Waszkowycz Bohdan, Wei Binqing
Abstract excerpt
A potent inhibitor of PI3Kδ that is ≥ 200 fold selective for the remaining three Class I PI3K isoforms and additional kinases is described. The hypothesis for selectivity is illustrated through structure activity relationships and crystal structures of compounds bound to a K802T mutant of PI3Kγ. Pharmacokinetic data in rats and mice support the use of 3 as a useful tool compound to use for in vivo studies.
Read the complete abstract on PubMedTopics
Share this publication in a Topic to start or enrich a Post.