Pharmacophores for Amyloid Fibers Involved in Alzheimer's Disease

A pharmaceutical composition comprising one or more of the compounds BAF4, BAF8, BAF11, BAF12, BAF14, BAF30 or BAF31, as shown in FIG. 18, or the derivatives of BAF11—the isomer, σR1, σR3 or ΔOHσR—as shown in FIG. 19, or the derivative of BAF30-αR1—as shown in FIG. 20, or a pharmaceutically acceptable salt, hydrate, solvate or metal chelate thereof, and a pharmaceutically acceptable carrier.

A method for determining the presence of Aβ or tau oligomers or fibers in a sample, comprising contacting a sample suspected of comprising such fibers with an effective amount of one or more of BAF4, BAF8, BAF11, BAF12, BAF14, BAF30 or BAF31, as shown in FIG. 18, or the derivatives of BAF11—the isomer, σR1, σR3 or ΔOHσR—as shown in FIG. 19, or the derivative of BAF30σR1—as shown in FIG. 20, or a pharmaceutically acceptable salt, hydrate, solvate or metal chelate thereof, wherein the compound is detectably labeled;

• and
• measuring the amount of bound label in the sample,
• wherein a statistically significantly higher amount of label than that in a control sample lacking the fibers indicates the presence of the fibers in the sample.

A method for detecting the presence of Aβ or tau fibers in a subject, comprising introducing into the subject a compound with an effective amount of one or more of the compounds BAF4, BAF8, BAF11, BAF12, BAF14, BAF30 or BAF31, as shown in FIG. 18, or the derivatives of BAF11—the isomer, σR1, σR3 or ΔOHσR—as shown in FIG. 19, or the derivative of BAF30-αR1— as shown in FIG. 20, or a pharmaceutically acceptable salt, hydrate, solvate or metal chelate thereof, wherein the compound is labeled with a nuclide that can be detected by PET;

• and
• measuring the amount of bound label in the brain by PET,
• wherein a statistically significantly higher signal than that in a control sample lacking the fibers indicates the presence of the fibrils in the brain of the subject.

A method for reducing or inhibiting amyloid-based cellular toxicity, comprising contacting amyloid protofilaments with an effective amount of BAF4, BAF8, BAF11, BAF12, BAF14, BAF30 or BAF31, as shown in FIG. 18, or the derivatives of BAF11—the isomer, σR1, σR3 or ΔOHσR—as shown in FIG. 19, or the derivative of BAF30-σR1— as shown in FIG. 20, or a pharmaceutically acceptable salt, hydrate, solvate or metal chelate thereof.

A method for treating an amyloid-mediated disease or condition, comprising administering to a subject having or likely to have the disease or condition an effective amount of BAF4, BAF8, BAF11, BAF12, BAF14, BAF30 or BAF31, as shown in FIG. 18, or the derivatives of BAF11—the isomer, σR1, σR3 or ΔOHσR—as shown in FIG. 19, or the derivative of BAF30-αR1— as shown in FIG. 20, or a pharmaceutically acceptable salt, hydrate, solvate or metal chelate thereof.

A computer readable medium providing the structural representation of a co-crystal of a protofilament of an amyloid protein with a small molecule that is known to bind to the amyloid protein.

A kit for detecting the presence of Abeta or tau in a sample, comprising a compound of the invention in a container.