Patent ID: 8450070

Claim:
A method for screening for a cell protecting agent, which comprises: (1) measuring whether a test compound modulates the binding of Hsp90 to an imidazothiazine derivative, (2) contacting said test compound with a human normal articular chondrocyte or an extract of said cell, and measuring either i) the amount of expression of Hsp40, Hsp70, or Hsp90 induced by the test compound or ii) the degree to which the test compound disrupts an Hsp90/HSF-1 complex, (3) contacting said test compound with a human normal articular chondrocyte or an extract of said cell and measuring the amount of degradation of an Hsp90 client protein induced by the test compound, wherein the Hsp90 client protein is one or more proteins selected from the group consisting of a glucocorticoid receptor, Akt, and cycline dependent kinase 4, and (4) selecting a test compound that modulates binding of Hsp90 to the imidazothiazine derivative in step (1), and either induces expression of an Hsp in step (2)(i) or disrupts an Hsp90/HSF-1 complex in step (2)(ii), and does not degrade an Hsp90 client protein in step (3); wherein the imidazothiazine derivative is N-[(1Z)-5,6-dimethyl-3-oxo-8-[(4,4,5,5,5-pentafluoropentyl)sulfanyl]-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-1-ylidene]-4-methylbenzenesulfonamide or 5-[[(1Z)-5,6-dimethyl-3-oxo-1-([[4-(trifluoromethyl)phenyl]sulfonyl]imino-)-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-8-yl]sulfanyl]pentanoic acid; and wherein the Hsp90 or the imidazothiazine derivative is bound to a carrier selected from the group consisting of insoluble polysaccharides of agarose, dextran and cellulose, synthetic resins of polystyrene, polyacrylamide and silicone, and glass.