Structure-activity relationship of isoform selective inhibitors of Rac1/1b GTPase nucleotide binding.

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Beausoleil E, Chauvignac C, Taverne T, Lacombe S, Pognante L, Leblond B, Pallares D, Oliveira CD, Bachelot F, Carton R, Peillon H, Coutadeur S, Picard V, Lambeng N, Desire L, Schweighoffer F

Structure-activity relationship of isoform selective inhibitors of Rac1/1b GTPase nucleotide binding.

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5594-8. doi: 10.1016/j.bmcl.2009.08.037. Epub 2009 Aug 13.

PubMed ID

19716293 [ View in PubMed

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Abstract

The synthesis of a series of berberine, phenantridine and isoquinoline derivatives was realized to explore their Rho GTPase nucleotide inhibitory activity. The compounds were evaluated in a nucleotide binding competition assay against Rac1, Rac1b, Cdc42 and in a cellular Rac GTPase activation assay. The insertion of 19 AA in the splice variant Rac1b is shown to be sufficient to introduce a conformational difference that allows compounds 4, 21, 22, and 26 to exhibit selective inhibition of Rac 1b over Rac1.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Guanosine-5'-Diphosphate	Ras-related C3 botulinum toxin substrate 1	IC 50 (nM)	2700	N/A	N/A	Details