The reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors.
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Nordhoff S, Cerezo-Galvez S, Feurer A, Hill O, Matassa VG, Metz G, Rummey C, Thiemann M, Edwards PJ
The reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors.
Bioorg Med Chem Lett. 2006 Mar 15;16(6):1744-8. Epub 2006 Jan 11.
- PubMed ID
- 16376544 [ View in PubMed]
- Abstract
The co-crystal structure of beta-phenethylamine fragment inhibitor 5 bound to DPP-IV revealed that the phenyl ring occupied the proline pocket of the enzyme. This finding provided the basis for a general hypothesis of a reverse binding mode for beta-phenethylamine-based DPP-IV inhibitors. Novel inhibitor design concepts that obviate substrate-like structure-activity relationships (SAR) were thereby enabled, and novel, potent inhibitors were discovered.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) (S)-2-[(R)-3-amino-4-(2-fluorophenyl)butyryl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide Dipeptidyl peptidase 4 IC 50 (nM) 23 7.4 25 Details 1-(1-phenylcyclopentyl)methylamine Dipeptidyl peptidase 4 IC 50 (nM) 33000 7.4 25 Details N-({(2S)-1-[(3R)-3-AMINO-4-(2-FLUOROPHENYL)BUTANOYL]PYRROLIDIN-2-YL}METHYL)BENZAMIDE Dipeptidyl peptidase 4 IC 50 (nM) 90 7.4 25 Details