Thalidomide Analogues

Thalidomide analogues have been synthesized with the aim of developing drugs with better clinical efficacy and improved side effect profiles. These include thalidomide-template-based TNF-a inhibitors, which may be 50,000 times more effective in TNF-a inhibition. Two classes are described, according to inhibition of phosphodiesterase 4. Those without phosphodiesterase 4-inhibitory activity also co-stimulate T cells, although more potently than thalidomide (Corral and Kaplan 1999). However, there have been no reports to date of their clinical use in lupus, although they have been used in therapy of myeloma (M. Kazmi, personal communication). As the exact mechanisms for the efficacy of thalidomide in lupus are not known, it is difficult to know which properties would be important to retain in the analogue.

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