Amyloid-binding compounds and methods of use thereof
A method of screening for amyloid-binding compounds, amyloid-binding compounds, and a method of detecting amyloid-β (Abeta) plaques in a subject are disclosed. The method of screening for amyloid-binding compounds includes combining amyloid, a dye, and at least one test compound to form a sample solution; equilibrating the sample solution; measuring a fluorescence signal of the sample solution; and comparing the measured fluorescence signal of the sample to a control; wherein attenuation of the fluorescence signal, as compared to the control, indicates that one or more of the test compounds bind amyloid. The amyloid-binding compound includes a compound detected by the screening method. The method of detecting amyloid-β (Abeta) plaques in a subject includes administering one or more of the amyloid-binding compounds to the subject, and detecting the compound within the subject.
1 . An amyloid-binding compound comprising a phenothiazine core;
an acyclic nitrogen atom that is not directly attached to the phenothiazine core; and
a positron emission tomography (PET) radioisotope label selected from [ 11 C]carbon, or [ 18 F]fluoride;
wherein the radioisotope label is attached to said acyclic nitrogen atom.
2 . The compound of claim 1 , wherein the ring nitrogen at position 10 of the phenothiazine core is attached to an N,N-dimethylpropan-2-amine moiety.
3 . A compound selected from:
wherein the compound further comprises a positron emission tomography (PET) radioisotope label attached to a nitrogen atom that is not part of the phenothiazine core.
4 . The compound of claim 1 , wherein the radioisotope is [ 11 C]carbon.
5 . A method of detecting amyloid-β (Abeta) plaques in a subject, the method comprising:
administering one or more of the compounds of claim 1 to the subject; and
detecting the compound within the subject through autoradiography.
6 . A compound of claim 1 , wherein the amyloid-binding compound is selected from: