Abstract: Antibodies specific for uPAR and uPA-uPAR complexes in the form of radioconjugates with alpha particle-emitting radionuclides are disclosed as is their use in treating severe respiratory diseases such as severe COVID-19.

Abstract: A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivates, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis. The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

Abstract: The present invention relates to antibodies, and antigen-binding fragments thereof, specific for urokinase-type plasminogen activator receptor (uPAR) and uses thereof for the treatment or prevention of cancer. In particular, the antibodies of the invention are specific for a particular epitope on uPAR. These antibodies interfere with uPAR signaling. Such antibodies are used in diagnostic and therapeutic methods, particularly against cancer.

Abstract: Antibodies or other ligands specific for the binary uPA-uPAR complexes, for ternary complexes comprising uPA-uPAR and for complexes of uPAR and proteins other than uPA such as integrins inhibit the interaction of uPA and uPAR with additional molecules with which the complexed interact. Such antibodies or other ligands are used in diagnostic and therapeutic methods, particularly against cancer.

Abstract: The current invention provides novel thiotungstate derivatives, methods of making novel thiotungstate derivatives, pharmaceutical compositions of novel thiotungstate derivatives, methods of using novel thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders and obesity and methods of using pharmaceutical compositions of thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-?B dysregulation.

Abstract: A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivates, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis. The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

Abstract: A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivatives, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis. The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

Abstract: Inhibitors of angiogenesis are disclosed as being useful therapeutics for treating various aspects of inflammatory bowel disease, in particular Crohn's Disease. A method for decreasing the magnitude of intestinal inflammation or inflammatory infiltrate in bowel tissue, a method for lowering systemic or gut-associated levels of a proinflammatory cytokine in a subject, a method for reducing microvessel density in fixed bowel tissue sections and a method for treating an inflammatory bowel disease are disclosed. Preferred agents to achieve the foregoing are pentapeptides that include Pro-His-Ser-Cys-Asn (SEQ ID NO:1) and variants or derivatives thereof.

Abstract: Urokinase-type plasminogen activator (uPA) binds its cellular receptor (uPAR) with high affinity, thus localizing the generation of plasmin from plasminogen on the surface of a variety of cells. Disclosed herein is the structure of suPAR (uPAR1-277) complexed with the amino terminal fragment (ATF) of uPA (uPA1-143) at a resolution of 1.9 ú by X-ray crystallography. Three consecutive domains of uPAR (D1, D2 and D3) form the shape of a thick-walled teacup with a cone shape cavity in the middle, which has a wide opening (25 ú) and large depth (14 ú). uPA1-143 inserts into the cavity of uPAR and forms a large interface. The structure provides the basis for high affinity binding between uPA and uPAR and suggests the D1 and D2 domain of uPAR and the GFD domain of uPA (uPA7-43) are primarily responsible for uPA-uPAR binding. This structure presents the first high resolution view of uPA-uPAR interaction, and provides, among other things, a new platform for designing uPA-uPAR inhibitors/antagonists.

Abstract: Antibodies or other ligands specific for the binary uPA-uPAR complexes, for ternary complexes comprising uPA-uPAR and for complexes of uPAR and proteins other than uPA such as integrins inhibit the interaction of uPA and uPAR with additional molecules with which the complexed interact. Such antibodies or other ligands are used in diagnostic and therapeutic methods, particularly against cancer.

Abstract: The present invention in the field of biochemistry and medicine is directed to novel methods for identifying molecules, typically proteins, that move to the cell surface when cells are stimulated or stressed can act as receptors even thought they are not transmembrane molecules and normally originate in the cytosol. Such molecules are useful targets for development of agents that can image or treat tumors or other pathologies. Methods to detect or identify such proteins that have translocated to the cell surface when cells are stressed by an angiogenic environment, environmental stresses, the stimulation of cell proliferation and differentiation, or after exposure to certain drugs such as cancer chemotherapeutics, are disclosed.

Abstract: A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivatives, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis. The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

Abstract: Acid addition salts of Ac—PHSCN—NH2, methods of making acid addition salts of Ac—PHSCN—NH2, pharmaceutical compositions of acid addition salts of Ac—PHSCN—NH2, methods of using acid addition salts of Ac—PHSCN—NH2 and pharmaceutical compositions thereof to treat diseases associated with angiogenesis and aberrant vascularization and methods of preventing degradation of Ac—PHSCN—NH2 by salt formation are provided herein.

Abstract: The present invention relates to antibodies, and antigen-binding fragments thereof, specific for urokinase-type plasminogen activator receptor (uPAR) and uses thereof for the treatment or prevention of cancer. In particular, the antibodies of the invention are specific for a particular epitope on uPAR. These antibodies interfere with uPAR signaling. Such antibodies are used in diagnostic and therapeutic methods, particularly against cancer.

Abstract: Though copper is elevated in the tumor tissue and plasma of patients with various malignancies, the molecular targets for copper binding agents in angiogenesis and tumor progression remain poorly understood. It is disclosed that one anti-angiogenic target for the copper binding agent tetrathiomolybdate is intracellular CuZn-superoxide dismutase (SOD1). A second generation tetrathiomolybdate analog, ATN-224, inhibits endothelial cell (EC) proliferation in vitro, binds to SOD1 and inhibits its activity without displacing bound copper ATN-224 can accumulate in ECs and inhibit CuZnSOD activity with an IC50 similar to the IC50 for EC proliferation, resulting in increased generation of intracellular reactive oxygen species. Inhibition of EC proliferation by ATN-224 in vitro is substantially reversed by a synthetic porphyrin SOD mimetic. Similar results were observed in vivo, where inhibition of angiogenesis by ATN-224 in a Matrigel plug model was also reversed by MnTBAP.

Abstract: Human kininogen domain 3 (HK-D3) polypeptides and biologically active variants and derivatives of HK-D3 are anti-angiogenic. These molecules are used to inhibit angiogenesis or treat a disease or condition in which angiogenesis is pathogenic. Because of their anti-angiogenic potential, these molecules compounds are useful in the treatment of cancer by inhibiting or reversing the growth of primary or metastatic tumors.

Abstract: Human kininogen domain 3 (HK-D3) polypeptides and biologically active variants and derivatives of HK-D3 are anti-angiogenic. These molecules are used to inhibit angiogenesis or treat a disease or condition in which angiogenesis is pathogenic. Because of their anti-angiogenic potential, these molecules are useful in the treatment of cancer by inhibiting or reversing the growth of primary or metastatic tumors.

Abstract: A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivatives, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis. The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

Abstract: A uPAR-targeting protein or peptide is diagnostically or therapeutically labeled and used in methods of diagnosis of therapy. The labeled protein or peptide preferably has the following properties: it comprises at least 38 amino acid residues, including residues 13-30 of the uPAR-binding site of uPA; competes with labeled DFP-uPA for binding to a cell or molecule that has a binding site for uPA, and has an IC50 value of about 10 nM or less; and is not a fusion protein wherein the uPA peptide is fused to another non-uPA protein or peptide. Preferred molecules are uPA, scuPA, tcuPA, an N-terminal fragment of uPA, residues 1-135, an N-terminal fragment of uPA, residues 1-143, an N-terminal fragment of uPA, residues 1-43; or an N-terminal fragment of uPA, residues 4-43. Detectable labels include a radionuclide, a PET-imageable agent, an MRI-imageable agent, a fluorescer, a fluorogen, a chromophore, a chromogen, a phosphorescer, a chemiluminescer or a bioluminescer.

Abstract: uPAR-targeting cyclic peptide compounds have 11 amino acids that correspond to human uPA(20-30) [SEQ ID NO:2], or are substitution variants at selected positions. The N and C terminal residues of these peptides are joined by a linking group L, so that the linear dimension between the &agr;-carbons of the first and the eleventh amino acids is between about 4 and 12 Angstrom units. These cyclic peptides may be further conjugated to diagnostic labels or therapeutic moieties such as radionuclides. Such compounds are useful for targeting uPAR expressed in pathological tissues and for inhibiting the binding of uPA to the uPAR. The pharmaceutical and therapeutic compositions inhibit cell migration, cell invasion, cell proliferation or angiogenesis, or induce apoptosis, and are thus useful for treating diseases or condition associated with undesired cell migration, invasion, proliferation, or angiogenesis, most notably cancer. The cyclic peptides are also used to detect and isolate cells expressing uPAR.