A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 31/4995 (2006.01) A61K 31/4985 (2006.01) A61K 31/7088 (2006.01) C07K 14/705 (2006.01) C07K 14/72 (2006.01) C12N 9/02 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2402439
The present invention relates to new methods of modifying drug clearance and avoiding multi-drug resistance by modifying SXR activity. SXR is a transcriptional activator of MDR1, cytochrome P40-3A4 and cytochrome P40 2C8. SXR activation can significantly increase the metabolic inactivation and efflux of a wide range of chemotherapeutic agents, for example taxanes. Reducing and/or preventing SXR activation therefore diminishes drug resistance and drug clearance and forms the basis of important therapeutic methods which increase the performance of drugs, such as taxanes. Screening and drug identification methods are described which can identify drugs which are not susceptible to SXR related inactivation and increased efflux. In addition, drugs which can reduce these effects for other agents are provided.
L'invention concerne de nouveaux procédés pour modifier la clairance de médicaments et éviter la résistance aux médicaments multiples par la modification de l'activité de SXR. SXR est un activateur transcriptionnel de MDR1, P40-3A4 cytochrome et P40 2C8 cytochrome. L'activation de SXR peut augmenter sensiblement l'inactivation métabolique et la sortie d'une large gamme d'agents chimiothérapeutiques, par exemple, de taxanes. En réduisant et/ou en empêchant l'activation de SXR on diminue la résistance aux médicaments et la clairance des médicaments, ce qui à son tour jette les bases de nouveaux procédés thérapeutiques importants qui augmentent les performances de médicaments tels que les taxanes. L'invention décrit des procédés de criblage et d'identification des médicaments qui ne sont pas sensibles à l'inactivation et la sortie plus intenses liées à SXR. En outre, l'invention concerne des médicaments qui peuvent réduire ces effets.
Dussault Isabelle
Forman Barry M.
Synold Timothy W.
City Of Hope
Osler Hoskin & Harcourt Llp
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