Methods for identifying modulators of mda-7 mediated apoptosis

Details Methods for identifying modulators of mda-7 mediated apoptosis Methods for identifying modulators of mda-7 mediated apoptosis

C - Chemistry, Metallurgy

12

Q

C12Q 1/02 (2006.01) C07K 14/47 (2006.01) C07K 14/54 (2006.01) C12Q 1/68 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2491637

The present invention relates to the discoveries that apoptotic effects of the melanoma differentiation associated gene mda-7 (also known as interleukin-24, "IL-24") on malignant cells occur via the p38 MAPK pathway and members of the Growth Arrest and DNA Damage ("GADD") gene family but are substantially independent of the JAK/STAT pathway. Accordingly, the invention provides for methods for identifying apoptosis-modulating agents using assay methods which determine the ability of a test agent to increase or decrease expression of constituents of the mda-7 apoptosis pathway, preferably in a JAK/STAT substantially independent manner. Such agents may be small molecules or may be fragments, variants and/or derivatives of native MDA-7.

La présente invention à permis de mette en évidence que les effets apoptotiques du gène mda-7 associé à la différenciation des mélanomes (également connu en tant que interleukine-24, "IL-24") sur les cellule malignes se produisent par l'intermédiaire de la voie p38 MAPK et les éléments de la famille des gènes de l'arrêt de la croissance et de dommage à l'ADN (GADD) mais sont sensiblement indépendants de la voie JAK/STAT. En conséquence, l'invention se rapporte à des procédés d'identification d'agents modulateurs de l'apoptose faisant appel à des procédés d'analyse qui déterminent la capacité d'un agent à l'essai à accroître ou réduire l'expression des constituants de la voie de l'apoptose mda-7, de préférence de manière sensiblement indépendante de JAK/STAT. Ces agents peuvent être de petites molécules ou peuvent être des fragments, des variants et/ou des dérivés du MDA-7 natif.

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