Exploring the PI3K alpha and gamma binding sites with 2,6-disubstituted isonicotinic derivatives.

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Cherian PT, Koikov LN, Wortman MD, Knittel JJ

Exploring the PI3K alpha and gamma binding sites with 2,6-disubstituted isonicotinic derivatives.

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2215-9. doi: 10.1016/j.bmcl.2009.02.115. Epub 2009 Mar 4.

PubMed ID

19297156 [ View in PubMed

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Abstract

A homology model of the p110alpha catalytic subunit of PI3Kalpha was generated from the p110gamma crystal structure. Using this model, an isonicotinic scaffold was designed for chemically exploring the PI3Kalpha and gamma binding sites. A focused library of derivatives was synthesized and tested. The morpholine acids 5a and 5b proved to be the most potent analogs.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
LY-294002	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC 50 (nM)	1200	N/A	N/A	Details