Composition and methods for inhibiting cell survival

A - Human Necessities – 61 – K

Patent

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Details

A61K 51/00 (2006.01) A61K 31/15 (2006.01) A61K 31/195 (2006.01) A61K 31/714 (2006.01) A61K 33/26 (2006.01) A61K 38/17 (2006.01) A61K 38/19 (2006.01) A61K 47/48 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2516453

The present invention is directed to compositions and methods of making and using compositions that are useful for treating cells or conditions caused or exacerbated by cell survival mechanisms of the body, particularly conditions exacerbated by cell survival mechanisms involving NF-KB. The compositions and methods of the present invention comprise a sensitizing agent or a chemopotentiating agent. In this regard, cobalamin drug conjugates and NO donors act as chemopotentiating agents. Nitrosylcobalamin is particularly useful as a sensitizing or chemopotentiating agent, and methods utilizing nitrosylcobalamin prior to, simultaneous with and subsequent to radiation or chemotherapy are described, as are compositions which first release a nitrosylcobalamin compound or biologically active analog thereof, and then release the chemotherapeutic agent. Nitrosylcobalamin itself is a chemotherapeutic, and when administered in conjunction with other anti-cancer agents or techniques, a synergistic effect is seen.

La présente invention concerne des compositions et des techniques de fabrication et d'utilisation de ces compositions, qui conviennent pour traiter des cellules ou des états causés ou exacerbés par des mécanisme de survie cellulaire du corps, en particulier des états exacerbés par des mécanismes de survie cellulaire impliquant NF-KB. Ces compositions et ces techniques comprennent un agent de sensibilisation ou un agent chimiopotentialisant. A cet égard, les conjugués de médicament cobalamine et des donneurs NO agissent comme des agents de chimiopotentialisants. La nitrosylcobalamine convient particulièrement comme agent de sensibilisation ou chimiopozentialisant et, des techniques utilisant la nitrosylcobalamine avant, après ou en même temps qu'une radiothérapie ou qu'une chimiothérapie sont présentées, de même que des compositions qui d'abord libèrent un composé nitrosylcobalamine ou un analogue biologiquement actif de celui-ci et, ensuite libère l'agent chimiothérapeutique. La nitrosylcobalamine elle même est un agent chimiothérapeutique et, lorsqu'on l'administre avec d'autres agents anticancéreux ou avec d'autres techniques, on constate un effet synergique..

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