Farnesyl protein transferase inhibitors targeting the catalytic zinc for enhanced binding.

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Njoroge FG, Vibulbhan B, Pinto P, Strickland C, Kirschmeier P, Bishop WR, Girijavallabhan V

Farnesyl protein transferase inhibitors targeting the catalytic zinc for enhanced binding.

Bioorg Med Chem Lett. 2004 Dec 6;14(23):5877-80.

PubMed ID

15501060 [ View in PubMed

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Abstract

Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring, FT inhibitors with activities in the picomolar range have been achieved as exemplified by compounds 12a and 12b. An X-ray structure of 11b bound to FT shows the enhanced activity is a result of interacting with the active-site zinc.

DrugBank Data that Cites this Article

Binding Properties

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