Invention Grant
- Patent Title: Homomultivalent and heteromultivalent inhibitors of prostate specific membrane antigen (PSMA) and uses thereof
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Application No.: US15187274Application Date: 2016-09-08
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Publication No.: US09884132B2Publication Date: 2018-02-06
- Inventor: Martin G. Pomper , Sangeeta Ray , Ronnie C. Mease , Hassan Shallal
- Applicant: THE JOHNS HOPKINS UNIVERSITY
- Applicant Address: US MD Baltimore
- Assignee: THE JOHNS HOPKINS UNIVERSITY
- Current Assignee: THE JOHNS HOPKINS UNIVERSITY
- Current Assignee Address: US MD Baltimore
- Agency: Michael Best & Friedrich LLP
- Agent Jeffrey W. Childers
- Main IPC: A61K51/08
- IPC: A61K51/08 ; C07K5/02 ; C07K5/09 ; A61K38/06 ; A61K45/06 ; C07D249/04 ; C07K5/097 ; A61K51/04 ; A61K38/00

Abstract:
The present invention provides bivalent and multivalent ligands with a view to improving the affinity and pharmacokinetic properties of a urea class of PSMA inhibitors. The compounds and their synthesis can be generalized to multivalent compounds of other target antigens. Because they present multiple copies of the pharmacophore, multivalent ligands can bind to receptors with high avidity and affinity, thereby serving as powerful inhibitors. The modular multivalent scaffolds of the present invention, in one or more embodiments, contains a lysine-based (∝, ε-) dialkyne residue for incorporating two or more antigen binding moieties, such as PSMA binding Lys-Glu urea moieties, exploiting click chemistry and one or more additional lysine residues for subsequent modification with an imaging and/or therapeutic nuclides or a cytotoxic ligands for tumor cell killing.
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