Compounds, compositions and methods for promoting or inhibiting
angiogenesis, and screening methods for identifying compounds are
disclosed. The compounds bind to F1 ATP synthase particularly to the
alpha and/or beta subunits of F1 ATP synthase. When bound to these
subunits, they can function as angiostatin agonists, antagonists, partial
agonists, inverse agonists, or allosteric modulators. When the compounds
mimic or enhance the activity of angiostatin, they inhibit angiogenesis.
When the compounds inhibit the ability of angiostatin to bind F1 ATP
synthase and are either inactive at inhibiting angiogenesis or directly
promote angiogenesis, or if they inhibit the activity of angiostatin,
they promote angiogenesis. The compounds can be, for example, antibodies,
antibody fragments, enzymes, peptides, nucleic acids such as
oligonucleotides, or small molecules. The antibodies can be monoclonal,
humanized, or polyclonal antibodies. The compounds can be conjugated to
or combined with various cytotoxic agents and/or labeled compounds.
Methods for promoting angiogenesis can be used to introduce vasculature
to areas in a patient that can benefit from such increased vasculature.
Methods for inhibiting angiogenesis can be used to treat disorders
mediated by angiogenesis, for example, tumors, autoimmune disorders such
as rheumatoid arthritis, and the like.