2bed
| |||||||
| , resolution 2.700Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | Fnta (Rattus norvegicus), Fntb (Rattus norvegicus) | ||||||
| Activity: | Protein farnesyltransferase, with EC number 2.5.1.58 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of FPT bound to inhibitor SCH207736
OverviewOverview
Benzocycloheptapyridine tricyclic compounds with piperazine or substituted piperidine moieties extending either from the 5- or 6-position of the tricyclic bridgehead exhibited enhanced FTase activity: this resulted from favorable binding of the ligand nitrogen with the catalytic zinc found in the FTase. A single isomer at C-11 with piperazine adduct extending from the 6-position, compound 24, exhibited excellent FTase activity with IC50 = 0.007 microM, soft agar IC50 = 72 nM, and Rat AUC(PO, 10 mpk) = 4.0 microM x h. X-ray of (-)-[8-chloro-6-(1-piperazinyl)-1H-benzo[5,6]]cyclohepta[1,2-b]pyridine-11 -yl]-1-(methylsulfonyl)piperidine 24 bound to Ftase revealed favorable interaction between piperazine nitrogen and catalytic zinc atom.
About this StructureAbout this Structure
2BED is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
Enhanced FTase activity achieved via piperazine interaction with catalytic zinc., Njoroge FG, Vibulbhan B, Pinto P, Strickland C, Bishop WR, Nomeir A, Girijavallabhan V, Bioorg Med Chem Lett. 2006 Feb 15;16(4):984-8. Epub 2005 Nov 16. PMID:16298128
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