NF-kappaB activation inhibitors, and their pharmaceutical uses

Abstract

Compounds inhibiting the activation of the nuclear factor κB (NF-κB) are used for the preparation of medications adapted for the treatment of malignant hemopathies and solid tumors, and for the prevention of the appearance or the treatment, of phenomena of resistance to cytotoxic molecules used in the scope of treatment of the above pathologies, appearing in patients treated with these molecules when the latter are adapted to activate NF-κB.

1 . A method treating a patient having or subject to developing malignant hemopathies or solid tumors and/or to treat resistance to cytotoxic molecules of said treatments, comprising administering an effective amount of a compound that inhibits the activation of the nuclear factor κB (NF-κB).  
     
     
         2 . The method according to  claim 1 , further comprising one or several cytotoxic molecules usable in the scope of treatment of the above-mentioned pathologies and adapted to activate the NF-κB factor.  
     
     
         3 . The method according to  claim 2 , wherein said compounds inhibiting the activation of MF-κB are connected specifically to the transmembranal receptors of the cytokins of class I in the cells of the organism.  
     
     
         4 . The method according to  claim 1 , wherein said compound is a recombinant human erythropoietin such as encoded by the nucleotide sequence SEQ ID NO 3, or by any nucleotide sequence derived from this latter by degeneracy of the genetic code and being nevertheless capable of encoding for human erythropoietin whose sequence in amino acids is represented by SEQ ID NO 4, said erythropoietin being obtained by transformation of appropriate cells with the help of vectors contained in a nucleotide sequence as described above, recovery of the recombinant protein produced by said cells, and purification; 
 or any peptide sequence derived by addition and/or deletion and/or substitution of one or several amino acids of the sequence SEQ ID NO 4, and preserving the property of inhibiting the activation of NF-κB.    
     
     
         5 . The method according to  claim 1 , wherein said compounds are in combination with one or several cytotoxic molecules adapted to activate the NF-κB factor, selected from: 
 cytokines,    anthracyclines, including daunomycin, and dauxorubicin,    vinca-alkaloids, such as vinblastine and vincristine,    paclitaxel (or Taxel, DCI).    
     
     
         6 . The method according to  claim 1 , said compound is administered with a dosage of the cytotoxic molecules used in combination with said compounds in about 2 to about 5 times less than the dosage of these same molecules used alone in the scope of treatment of malignant hemopathies and solid tumors.