Compounds for Treating Tauopathies and Restless Leg Syndrome and Methods of Using and Screening for Same

A method of enhancing the ability of receptor-type tyrosine-protein phosphatase delta (PTPRD) to dephosphorylate a kinase, the method comprising contacting PTPRD with an effective amount of a compound represented by Formula (I):

• or a pharmaceutically acceptable salt thereof;
• wherein R1 is hydrogen or —CH3;
• R2, R3, and R5 are each independently hydrogen or —OH;
• and R4 is hydrogen, —OH, or —OCH3.

A kit comprising:

• a) a compound represented by Formula (I) in an amount effective for treating a tauopathy or restless leg syndrome in a subject,
• or a pharmaceutically acceptable salt thereof;
• wherein R1 is hydrogen or —CH3;
• R2, R3, and R5 are each independently hydrogen or —OH;
• and R4 is hydrogen, —OH, or —OCH3;
• and
• b) instructions for treating the tauopathy or restless leg syndrome and/or an effective amount of a compound known for treating the tauopathy or restless leg syndrome.

A method of screening for positive allosteric modulators of the ability of a receptor-type tyrosine-protein phosphatase delta (PTPRD) to dephosphorylate a kinase, the method comprising:

• a) contacting the PTPRD with a test compound in the presence of the phosphorylated kinase;
• and
• b) measuring any orthophosphate release from the kinase;
• wherein the PTPRD comprises a phosphatase D1 domain having at least 80% amino acid identity with SEQ ID NO:
• 1;
• and
• wherein the kinase is GSKα or GSKβ comprising a polypeptide having at least 80% amino acid identity with SEQ ID NO:
• 2 or CDK5 comprising a polypeptide having at least 80% amino acid identity with SEQ ID NO:
• 4.