The synthesis and biological evaluation of a series of potent dual inhibitors of farnesyl and geranyl-Geranyl protein transferases.

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Tucker TJ, Abrams MT, Buser CA, Davide JP, Ellis-Hutchings M, Fernandes C, Gibbs JB, Graham SL, Hartman GD, Huber HE, Liu D, Lobell RB, Lumma WC, Robinson RG, Sisko JT, Smith AM

The synthesis and biological evaluation of a series of potent dual inhibitors of farnesyl and geranyl-Geranyl protein transferases.

Bioorg Med Chem Lett. 2002 Aug 5;12(15):2027-30.

PubMed ID

12113834 [ View in PubMed

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Abstract

We have prepared a series of potent, dual inhibitors of the prenyl transferases farnesyl protein transferase (FPTase) and geranyl-geranyl protein transferase I (GGPTase). The compounds were shown to possess potent activity against both enzymes in cell culture. Mechanistic analysis has shown that the compounds are CAAX competitive for FPTase inhibition but geranyl-geranyl pyrophosphate (GGPP) competitive for GGPTase inhibiton.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
L-778123	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	IC 50 (nM)	99	N/A	N/A	Details
L-778123	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	IC 50 (nM)	2	N/A	N/A	Details