Fgf21 derivatives with albumin binder a-b-c-d-e- and their use

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 14/50 (2006.01) A61K 47/48 (2006.01) A61P 3/00 (2006.01) C07K 17/02 (2006.01) A61K 38/18 (2006.01)

Patent

CA 2748593

The present invention relates to Fibroblast Growth Factor 21 (FGF21), more in particular to derivatives of FGF21 compounds having an albumin binder of the formula A-B- C-D-E- covalently attached. The invention also relates to novel FGF21 analogues, as well as to the pharmaceutical use of these FGF21 derivatives and analogues, in particular for the treatment of diabetes, dyslipidemia, obesity, cardiovascular diseases, metabolic syndrome, and/or Non Alcoholic Fatty Liver Disease (NAFLD). The derivatives of the invention are protracted, e.g. capable of maintaining a low blood glucose level for a longer period of time, capable of increasing the in vivo half-life of FGF2 1, and/or result in a lower clearance of FGF21. The derivatives of the invention are preferably furthermore of an improved oxidative stability.

La présente invention concerne le facteur de croissance fibroblastique 21 (FGF21) et, plus précisément, des dérivés de composés de type FGF21 caractérisés par leur association, par liaison covalente, à un agglutinant albumineux de formule A-B-C-D-E. L'invention concerne également des analogues inédits du FGF21, ainsi que l'utilisation pharmaceutique desdits dérivés et analogues du FGF21, en particulier en vue du traitement du diabète, de la dyslipidémie, de l'obésité, des maladies cardiovasculaires, du syndrome métabolique et/ou de la stéatose hépatique non alcoolique (SHNA). Les dérivés de l'invention présentent une action prolongée, c'est-à-dire qu'ils sont capables de maintenir la glycémie sanguine à un niveau bas pendant plus longtemps, ainsi que d'entraîner un allongement de la demi-vie du FGF21 in vivo et/ou une clairance plus faible du FGF21. Les dérivés de l'invention présentent, en outre et de préférence, une résistance à l'oxydation améliorée.

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