NF-kappaB activation inhibitors, and their pharmaceutical uses

a technology of nf-kappab and activation inhibitor, which is applied in the field of biological inhibitors of nf-kappab, can solve the problems of increasing the dosage of these medications, not allowing their direct use in therapeutic applications, aggravating the side effects observed in patients, etc., and achieves the effect of reducing the concentration of these latter drugs

Inactive Publication Date: 2005-12-08
CENT NAT DE LA RECHERCHE SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011] The present invention results from the discovery by the inventors of new effects of the human growth hormone (HGH), also called somatotropin, namely, on the one hand that HGH, and other compounds connected specifically to the transmembrane receptors of class I cytokines, are inhibitors of the activation of NF-κB by a cytotoxic molecule, and, on the other hand, that HGH, and other above-mentioned compounds, permit potentiating the effects of cytotoxic molecules and hence reducing the concentrations of these latter in the field of therapeutic treatments.

Problems solved by technology

One of the counter-measures at present developed by clinicians is the increase of the dosage of these medications, with the result of aggravating the side effects observed in the patients.
Thus, this does not permit their direct use in therapeutic applications.
This technology is also in the state of development because of the complexity and the vectorization necessary for its good operation.

Method used

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  • NF-kappaB activation inhibitors, and their pharmaceutical uses
  • NF-kappaB activation inhibitors, and their pharmaceutical uses
  • NF-kappaB activation inhibitors, and their pharmaceutical uses

Examples

Experimental program
Comparison scheme
Effect test

example 4

4) EXAMPLE 4

[0092] To test the possibility of using the object of the present invention on non-lymphoid tumors, the inventors have used HGH to try to invert the “adriamycine resistant” pheno-type of cells isolated from a human ovarian adenocarcinoma IGROV / ADR (Benard J et coll., 1985, Cancer Res, 45:4970-4979).

[0093] As shown by FIG. 5, these cells are insensitive to the toxic effect of the daunomycin added to the culture (HGH groups 0 ng / ml). The addition of recombinant HGH (Saizen□, Serono laboratory) renders these cells sensitive to daunomycin, with a maximum effect observed for the lowest dose of HGH used here, namely 5 ml / ml.

[0094] These result proves on the one hand that the results of aggravated mortality can be obtained as well with recombinant exogenous HGH as with the transfected lines mentioned above, and that on the other hand, the present invention can be applied to non-lymphoid solid tumors.

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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.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a division of co-pending application Ser. No. 09 / 856,796, filed on May 25, 2001, the entire contents of which are hereby incorporated by reference.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention has for its object the use of biological inhibitors of NF-κB, in the field of treating cancers, and more particularly malignant hemopathies or solid tumors. [0004] 2. Description of Related Art [0005] Numerous tumoral cells have developed sophisticated mechanisms permitting them to resist the effect of certain agents used in anti-cancer chemotherapy. One of the counter-measures at present developed by clinicians is the increase of the dosage of these medications, with the result of aggravating the side effects observed in the patients. Thus, for example, most of the leukemias and certain lymphomas are treated by the administration of anthracyclines (daunomycin, dauxorubicin) whose tox...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/00A61K31/337A61K31/475A61K31/65A61K38/00C12N15/09A61K38/18A61K38/19A61K38/27A61K45/00A61K45/06A61P35/00C07K14/505C07K14/52C07K14/61C12N15/16
CPCA61K31/00A61K31/337A61K31/475A61K31/704A61K38/1816A61K38/27A61K38/19A61K31/70A61K31/335A61K2300/00Y10S514/806A61P35/00
Inventor HIRSCH, FRANCOISHAEFFNER, ASTRID
Owner CENT NAT DE LA RECHERCHE SCI
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