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Methods and Pharmaceutical Compositions for the Treatment of Diseases Mediated by the NRP-1/OBR Complex Signaling Pathway

a technology of nrp1 and obr, which is applied in the direction of drug compositions, immunological disorders, metabolism disorders, etc., can solve the problems of obesity being considered a risk for many cancers and the role of obesity remains controversial

Inactive Publication Date: 2017-02-23
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +7
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text discusses the discovery of a new target for breast cancer treatment, namely Neuropilin-1 (NRP-1). This protein is involved in tumor progression and is connected to obesity and leptin, a hormone involved in the process. The inventors suggest that inhibiting the interaction of NRP-1 with its ligands could lead to increased leptin signaling and favor metastasis and shorten overall survival. The patent describes a screening method to test the effectiveness of substances in inhibiting the binding of NRP-1 to its ligands. This method allows for the identification of potential treatments for breast cancer and other cancers where NRP-1 is involved.

Problems solved by technology

In addition, data are accumulating showing that NRP-1 is involved in oncogenesis (Soker et al., 2001; Ellis et al, 2006), but its role remains controversial.
Obesity is considered a risk for many cancers.

Method used

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  • Methods and Pharmaceutical Compositions for the Treatment of Diseases Mediated by the NRP-1/OBR Complex Signaling Pathway
  • Methods and Pharmaceutical Compositions for the Treatment of Diseases Mediated by the NRP-1/OBR Complex Signaling Pathway
  • Methods and Pharmaceutical Compositions for the Treatment of Diseases Mediated by the NRP-1/OBR Complex Signaling Pathway

Examples

Experimental program
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Effect test

example 1

Neuropilin-1 (NRP-1) Induces Breast Cancer Metastasis Through its New Partners Leptin / OBR Complex: Identification of Nuclear NRP-1 Associated to Genes Sequences with RNA Polymerase II and Transcription Factor Binding Site

[0171]In Vitro and In Vivo Implication of NRP-1 and Leptin in Breast Cancer Cell Line Migration

[0172]First MBA-MB-231 and T47D breast cancer cells line were selected for their high and undetectable NRP-1 expression respectively and the expression of Leptin receptor (OBR). In order to investigate NRP-1 and Leptin association in breast cancer cell line migration, we proceeded to NRP-1 expression silencing in MDA-MB-231 using either siRNA or shRNA approaches or NRP-1 overexpression in T47D. In contrast to several published data, we were unable to observe MDA-MB-231 and T47D-NRP-1 proliferation under Leptin stimulation. Surprisingly, NRP-1 repression by RNA silencing induces MDA-MD-231 proliferation. In contrast Leptin induced MDA-MB-231 migration that was decreased in ...

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Abstract

The present invention relates to methods and pharmaceutical compositions for the treatment of diseases mediated by the NRP-1 / OBR complex signaling pathway. In particular, the present invention relates to a method for treating a disease selected from the group consisting of cancers, obesity and obesity related diseases, anorexia, autoimmune diseases and infectious diseases in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an antagonist of the NRP-1 / OBR signaling pathway.

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods and pharmaceutical compositions for the treatment of diseases mediated by the NRP-1 / OBR complex signaling pathway.BACKGROUND OF THE INVENTION[0002]Neuropilin-1 (NRP-1) a trans-membrane receptor that plays a central role in neuronal development (Fujisawa et al., 1995) has been subsequently shown to be also involved in blood vessel development as a co-receptor for two different types of ligands, the semaphorin (SEMA) family of axon guidance modulators and the vascular endothelial growth factor (VEGF) family of angiogenesis stimulators, respectively. NRP-1 needs to form complexes with receptors belonging to the plexin family, which serve as the signal-transducing element for the axonal repulsion and collapse of neuronal growth cones after SEMA binding to the NRP-1 / plexin complex (He and Tessier-Lavigne, 1997). NRP-1 also interacts as well with VEGF receptors (VEGFR) forming a complex, which can be activated by VEGF-A1...

Claims

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Application Information

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IPC IPC(8): C07K16/28A61K39/395G01N33/566A61K31/7105A61K31/713A61K45/06C12N15/113
CPCC07K16/2863A61K45/06A61K39/39558C12N15/1138A61K31/7105A61K31/713G01N2500/02C12N2310/14C12N2310/531C12N2320/31C07K2317/76G01N2333/71G01N33/566G01N2333/70503A61K38/17A61K31/4745A61P1/14A61P13/02A61P13/12A61P3/04A61P31/00A61P37/06A61P43/00A61P7/00Y02A50/30
Inventor BELAID-CHOUCAIR, ZAKIAHERMINE, OLIVIERGARRIDO-FLEURY, CARMENCOCHET, CLAUDEFILHOL-COCHET, ODILESEIGNEURIC, RENAUD
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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