Small molecule inhibitors of HLA-DR3 binding for treating autoimmune thyroiditis
A method for treating autoimmune thyroid disease is disclosed. The method comprises administering a molecule of molecular weight below 700 that inhibits the binding of the nonadecapeptide IPDNLFLKSDGRIKYTLNK (SEQ ID NO:1) to HLA-DRβ1-Arg74. Such compounds are found in the class of bisbenzylisoquinoline alkaloids represented by formula I
1. A method for treating, forestalling or reducing the risk of autoimmune thyroid disease comprising administering to a patient a compound of formula I
wherein
R 1 and R 2 are chosen independently from H and CH 3 , or, taken together R 1 and R 2 are —CH 2 —; and
R 3 , R 4 , R 5 , R 6 are chosen independently from H and CH 3 .
2. A method according to claim 1 comprising administering to a patient a compound of formula Ib
wherein
R 1 and R 2 are chosen independently from H and CH 3 , or, taken together R 1 and R 2 are —CH 2 —; and
R 3 and R 4 are chosen independently from H and CH 3 .
3. A method according to claim 2 wherein said compound of formula I is cepharanthine:
4. A method according to claim 1 wherein said autoimmune thyroid disease is Hashimoto's thyroid disease.
5. A method according to claim 1 wherein said autoimmune thyroid disease is Grave's Disease.
6. A method according to claim 1 wherein said patient carries an HLA-DRβ1-Arg74 variant.
7. A method according to claim 2 wherein said autoimmune thyroid disease is Hashimoto's thyroid disease.
8. A method according to claim 3 wherein said autoimmune thyroid disease is Hashimoto's thyroid disease.
9. A method according to claim 2 wherein said autoimmune thyroid disease is Grave's Disease.
10. A method according to claim 3 wherein said autoimmune thyroid disease is Grave's Disease.
11. A method according to claim 2 wherein said patient carries an HLA-DRβ1-Arg74 variant.
12. A method according to claim 3 wherein said patient carries an HLA-DRβ1-Arg74 variant.