A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 31/5375 (2006.01) A61K 31/133 (2006.01) A61K 31/167 (2006.01) A61P 35/00 (2006.01) C12Q 1/00 (2006.01)
Patent
CA 2335941
A method of treating a hyperproliferative disorder in a subject in need of such treatment, comprising administering to said subject, in combination, a treatment effective amount of: (a) a ceramide-generating retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) ceramide degredation inhibitor, such as compounds selected from the group consisting of (i) glucosylceramide synthesis inhibitors, (ii) sphingosine-1-phosphate synthesis inhibitors, and (iii) protein kinase C inhibitors. A preferred glucosyl ceramide synthesis inhibitor is 1- phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingosine-1-phosphate synthesis inhibitor is D-erytho-N,N- dimethylsphingosine. A preferred protein kinase C inhibitor is L-threo-dihydrosphingosine.
La présente invention concerne un traitement de trouble hyperproliférant, chez un sujet le requérant, qui comprend l'administration audit sujet, d'une quantité efficace d'un traitement combiné composé: (a) d'un rétinoïde générateur de céramide tel que le fenretinide ou un de ses sels acceptables sur le plan pharmaceutique; et (b) au moins d'un (et dans certaines réalisations au moins de deux) inhibiteur de dégradation de céramide tel que des composés choisi parmi (i) des inhibiteurs de synthèse de glucosylcéramide, (ii) d'inhibiteurs de synthèse de sphingosine-1-phosphate, et (iii) d'inhibiteurs de protéine kinase C. Un inhibiteur préféré de synthèse de céramide glucosyle est le 1-phényl-2-palmitoylamino-3-morpholino-1-propanol. Un inhibiteur préféré de synthèse de sphingosine-1-phosphate est le D-érythro-N,N-diméthylsphingosine. Un inhibiteur préféré de protéine kinase C est le L-thréo-dihydrosphingosine.
Cabot Myles
Maurer Barry James
Patrick Reynolds C.
Children's Hospital Of Los Angeles
John Wayne Cancer Institute
Sim & Mcburney
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