695172-01-1Relevant academic research and scientific papers
The first potent diphenyl phosphonate KLK4 inhibitors with unexpected binding kinetics
Van Soom, Jeroen,Cuzzucoli Crucitti, Giuliana,Gladysz, Rafaela,Van Der Veken, Pieter,Di Santo, Roberto,Stuyver, Ingmar,Buck, Victoria,Lambeir, Anne-Marie,Magdolen, Viktor,Joossens, Jurgen,Augustyns, Koen
, p. 1954 - 1958 (2015/11/17)
KLK4 is a serine protease from the kallikrein family that is involved in cancer progression. The diphenyl phosphonate warhead is intended to bind irreversibly with serine proteases, but unexpectedly, very potent KLK4 diphenyl phosphonate inhibitors were d
NOVEL KLK4 INHIBITORS
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Page/Page column 38, (2015/12/18)
The present invention relates to novel compounds and probes which have a common chemical structure necessary to obtain potent inhibitory activity against KLK4 and/or may be used for the detection of KLK4 peptides and their activity. It further relates to the use of these compounds and methods for inhibiting and/or detecting KLK4 activity in vitro and in vivo by making use of said probes or inhibitors. The compounds of the invention differ from prior art compounds at least in the presence of phenyl guanidine (instead of e.g. benzyl guanidine) and/or the presence of a heteroatom in the tail group, their combined presence unexpectedly leading to potent and selective KLK4 inhibitory activity.
Tuning activity-based probe selectivity for serine proteases by on-resin 'click' construction of peptide diphenyl phosphonates
Serim, Sevnur,Mayer, Susanne V.,Verhelst, Steven H. L.
, p. 5714 - 5721 (2013/09/12)
Activity-based probes (ABPs) are powerful tools for functional proteomics studies. Their selectivity can be influenced by modification of a recognition element that interacts with pockets near the active site. For serine proteases there are a limited numb
Inhibition of trypsin and urokinase by Cbz-amino(4-guanidinophenyl)methanephosphonate aromatic ester derivatives: The influence of the ester group on their biological activity
Sieńczyk, Marcin,Oleksyszyn, Józef
, p. 2886 - 2890 (2008/09/20)
The urokinase plasminogen activator is a trypsin-like serine protease, important in tumor development. Here, we report the synthesis and biochemical evaluation of selective and potent diaryl esters of phosphonic-type inhibitors for urokinase. We have found that the substituted phenyl ester ring has a strong influence on the inhibitory activity of these compounds. This led to the most potent phosphonic inhibitor for uPA synthesized to date.
A convenient synthesis of new α-aminoalkylphosphonates, aromatic analogues of arginine as inhibitors of trypsin-like enzymes
Sienczyk, Marcin,Oleksyszyn, Jozef
, p. 7251 - 7254 (2007/10/03)
A simple and efficient protocol for the synthesis of new N-protected α-aminoalkylphosphonic diphenyl esters - aromatic analogues of arginine - is presented. The crucial, guanylating step was achieved using S-ethyl-N,N′-di(Boc)isothiourea in chloroform and
Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator
Joossens,Van Der Veken,Lambeir,Augustyns,Haemers
, p. 2411 - 2413 (2007/10/03)
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 kapp value in the 103 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.
