New therapeutic use of 5-aminoimidazole-4-carboxamide...

A - Human Necessities – 61 – K

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A61K 31/7056 (2006.01) A61P 35/00 (2006.01) C07H 19/052 (2006.01)

Patent

CA 2479674

Acadesine (also known as AICA riboside or AICAR) does not inhibit apoptosis in lymphocytes, as it might be expected, but it induces apoptosis in B cells from patients with B-cell lymphoproliferative disorders such as B-cell chronic lymphocytic leukemia (B-CLL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and Waldenstrom syndrome (WS). T cells are not affected. This makes acadesine and its bioprecursors (eg. its mono-, di- and tri-5'--phosphates) useful as therapeutic agents for B-cell lymphoproliferative disorders in humans. The surprising feature that T cells are virtually not affected means that the side effect (immunosuppression) is minor, what represents a therapeutical advantage of acadesine over cladribine, fludarabine and other nucleosides known in the art.

Bien que l'acadésine (également appelée AICA riboside ou AICAR) n'inhibe pas l'apoptose chez les lymphocytes, ainsi qu'on pourrait le croire, elle induit l'apoptose chez les cellules B de patients souffrant de maladies lymphoprolifératives de type B, telles que la leucémie lymphatique chronique des cellules B (B-CLL), le lymphome splénique de la zone marginale (SMZL), le lymphome à cellules du manteau (MCL), le lymphome folliculaire (FL), le lymphome lymphoplasmocytaire (LPL) et le syndrome de Waldenstrom (WS). Les lymphocytes T ne sont pas affectés. Ceci transforme l'acadésine et ses bioprécurseurs (p.ex. ses mono-, di- et tri-5'-phosphates) en agents thérapeutiques utiles contre les maladies lymphoprolifératives chez les humains. L'étonnante caractéristique qui permet aux lymphocytes T de ne pas être affectés signifie que l'effet secondaire défavorable (immunosupression) est restreint, ce qui représente un avantage thérapeutique de l'acadésine sur la cladribine, la fludarabine et d'autres nucléosides connus dans la technique.

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