Combinations of inhibitors of farnesyl-protein transferase

Details Combinations of inhibitors of farnesyl-protein transferase Combinations of inhibitors of farnesyl-protein transferase

A - Human Necessities

61

K

A61K 38/07 (2006.01) A61K 38/03 (2006.01) A61K 38/05 (2006.01) A61K 38/06 (2006.01) A61K 38/55 (2006.01) A61K 45/00 (2006.01)

Patent

CA 2225255

The present invention relates to compositions comprising amounts of at least two therapeutic agents selected from a group consisting of a farnesyl protein transferase inhibitor which is an effective inhibitor of the enzyme because it is competitive with respect to the protein substrate of the enzyme and a farnesyl protein transferase inhibitor which is an effective inhibitor of the enzyme because it is competitive with respect to farnesyl pyrophosphate. Further contained in this invention are methods of inhibiting farnesyl-protein transferase and treating cancer in a mammal, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a farnesyl protein transferase inhibitor which is an effective inhibitor of the enzyme because it is a competitive inhibitor with respect to the protein substrate of the enzyme and a farnesyl protein transferase inhibitor which is an effective inhibitor of the enzyme because it is a competitive inhibitor with respect to farnesyl pyrophosphate, in amounts sufficient to achieve an additive or synergistic therapeutic effect. The invention also relates to methods of preparing such compositions.

L'invention concerne des compositions comprenant des quantités d'au moins deux agents thérapeutiques choisis dans un groupe constitué d'un inhibiteur de farnésyl-protéine transférase, lequel constitue un inhibiteur efficace de l'enzyme du fait qu'il se trouve en concurrence par rapport au substrat protéique de l'enzyme, et d'un inhibiteur de farnésyl-protéine transférase, lequel constitue un inhibiteur efficace de l'enzyme du fait qu'il se trouve en concurrence par rapport au farnésylpyrophosphate. L'invention concerne également des procédés d'inhibition de farnésyl-protéine transférase et de traitement du cancer chez un mammifère, lesquels procédés consistent à administrer audit mammifère, soit séquentiellement dans n'importe quel ordre soit simultanément, des doses d'au moins deux agents thérapeutiques choisis dans un groupe constitué d'un inhibiteur de farnésyl-protéine transférase, lequel constitue un inhibiteur efficace de l'enzyme du fait qu'il est un inhibiteur concurrentiel par rapport au substrat protéique de l'enzyme, et d'un inhibiteur de farnésyl-protéine transférase, lequel constitue un inhibiteur efficace de l'enzyme du fait qu'il est un inhibiteur concurrentiel par rapport au farnésyle pyrophosphate en des doses suffisantes pour obtenir un effet thérapeutique ou synergique. L'invention concerne en outre des procédés de préparation de ces compositions.

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