UPAR-antagonists and uses thereof
A molecular and dimer technology, applied in the field of urokinase-type plasminogen activator receptor inhibitors, can solve the problems that the importance of interaction is not discussed, and achieve the effect of excellent drug properties
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[0044] The invention will now be described by way of a non-limiting example with reference to the following figures.
[0045] figure 1 .Sketch showing the forced-proximity concept of the uPAR lock.
[0046] The function of uPAR in extracellular proteolysis mediated by uPA binding can be competitively inhibited by receptor binding to the growth factor-like domain (GFD) of uPA. The somatomodulin B domain (SMB) of VN can be exploited to competitively inhibit the function of uPAR in signal transduction mediated by VN binding. D1, D2 and D3 below are uPAR domains.
[0047] (A) GFD and SMB domains as competitive uPAR antagonists
[0048] Blocking uPAR function using a mixture of isolated GFD and SMB requires two sequential first-order intermolecular binding reactions (1 and 2), and two pathways can be used depending on whether GFD or SMB first binds to the receptor (A and B). The overall stability of the ternary uPAR:GFD:SMB complex and thus receptor inhibition is limited by t...
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