Development of irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator.

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Joossens J, Van der Veken P, Lambeir AM, Augustyns K, Haemers A

Development of irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator.

J Med Chem. 2004 May 6;47(10):2411-3.

PubMed ID

15115382 [ View in PubMed

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Abstract

In this letter we report the synthesis and biochemical evaluation of selective, irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator (uPA). A diphenyl phosphonate group was introduced on the substratelike peptide Z-d-Ser-Ala-Arg, and modification of the guanidine side chain was investigated. A guanylated benzyl group appeared the most promising side chain modification. A k(app) value in the 10(3) M(-1) s(-1) range for uPA was obtained, together with a selectivity index higher than 240 toward other trypsin-like proteases such as tPA, thrombin, plasmin, and FXa.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Amiloride	Urokinase-type plasminogen activator	IC 50 (nM)	107000	N/A	N/A	Details