Method for identifying modulators of the nrf2-keap1-are pathway

Details Method for identifying modulators of the nrf2-keap1-are pathway Method for identifying modulators of the nrf2-keap1-are pathway

G - Physics

01

N

G01N 33/53 (2006.01) C12Q 1/00 (2006.01) G01N 33/543 (2006.01) C12N 9/00 (2006.01) G01N 33/58 (2006.01)

Patent

CA 2667914

A method for identifying modulators of the Keapl -NrG-ARE pathway is described. In particular, an assay is described that identifies molecules that inhibit the binding of a labeled Nrf2 peptide with the kelch domain of the Keapl protein. Molecules that inhibit the binding are activators of the Keap 1 -Nrf2- ARE pathway. Activation of the Keap 1 -Nrf2- ARE pathway may result in an increased accumulation of Nrf2 and the subsequent induction of protective enzymes, for example, the phase 2 detoxification enzymes. Activators of the Keapl- NrG-ARE pathway are useful for combating oxidative stress-related disorders, such as those associated with cancer, emphysema, Huntington's disease, light-induced retinal damage, and stroke.

La présente invention concerne un procédé permettant d'identifier des modulateurs de la voie Keap1-NrG-ARE. L'invention concerne en particulier un essai qui identifie les molécules capables d'inhiber la liaison d'un peptide Nrf2 marqué avec le domaine kelch de la protéine Keap1. Les molécules inhibitrices de la liaison sont des activateurs de la voie Keap1-Nrf2-ARE. L'activation de la voie Keap1-Nrf2-ARE est susceptible de conduire à une accumulation accrue de Nrf2 et à l'induction subséquente d'enzymes protectrices, par exemple, les enzymes de détoxication de phase 2. Les activateurs de la voie Keap1-NrG-ARE se révèlent utiles pour lutter contre les troubles liés à un stress oxydant, tels que les troubles associés au cancer, à l'emphysème, à la maladie d'Huntington, à une lésion rétinienne induite par la lumière, et à un accident vasculaire cérébral.

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