Synthesis of phosphatidylinositol 3-kinase (PI3K) inhibitory analogues of the sponge meroterpenoid liphagal.

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Pereira AR, Strangman WK, Marion F, Feldberg L, Roll D, Mallon R, Hollander I, Andersen RJ

Synthesis of phosphatidylinositol 3-kinase (PI3K) inhibitory analogues of the sponge meroterpenoid liphagal.

J Med Chem. 2010 Dec 23;53(24):8523-33. doi: 10.1021/jm100531u. Epub 2010 Dec 1.

PubMed ID

21121631 [ View in PubMed

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Abstract

Analogues of the sponge meroterpenoid liphagal have been synthesized and evaluated for inhibition of PI3Kalpha and PI3Kgamma as part of a program aimed at developing new isoform-selective PI3K inhibitors. One of the analogues, compound 24, with IC(5)(0) values of 66 nM against PI3Kalpha and 1840 nM against PI3Kgamma, representing a 27-fold preference for PI3Kalpha, exhibited enhanced chemical stability and modestly enhanced potency and selectivity compared with the natural product liphagal.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Wortmannin	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC 50 (nM)	12	N/A	N/A	Details