Methods of inducing terminal differentiation

Details Methods of inducing terminal differentiation Methods of inducing terminal differentiation

A - Human Necessities

61

K

A61K 31/167 (2006.01) A61P 35/00 (2006.01) C07C 259/06 (2006.01)

Patent

CA 2478094

The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

Cette invention se rapporte à des procédés permettant d'induire sélectivement une différentiation terminale, une interruption de la croissance cellulaire et/ou une apoptose des cellules néoplasiques et/ou d'inhiber l'histone désacétylase (HDAC), grâce à l'administration de compositions pharmaceutiques contenant de puissants inhibiteurs de l'HDAC. La biodisponibilité orale des composés actifs contenue dans ces compositions pharmaceutiques est étonnamment élevée. En outre, ces compositions pharmaceutiques produisent de façon surprenante des niveaux sanguins thérapeutiquement efficaces élevés de ces composés actifs sur une période étendue. Cette invention concerne en outre un régime posologique quotidien sûr de ces compositions pharmaceutiques, qui est facile à suivre et qui produit une quantité thérapeutiquement efficace de ces inhibiteurs d'HDAC in vivo.

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