Compounds for stimulating p-glycoprotein function and uses thereof
AssigneeAngiochem Inc.
InventorsRichard Beliveau, Michel Demeule, Stephane Barakat, Jonathan Michaud-Levesque
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Abstract
The present invention is directed to polypeptides (e.g., fragments) derived from P-glycoprotein and caveolin-1 which are capable of inhibiting the interaction between these two proteins. Inhibition of this interaction leads to increase of efflux of compounds that are transported by P-gp. The invention further includes methods of treating patients having diseases that benefit from increased P-gp-mediated efflux. Such diseases include neoplasms such as cancer and neurological diseases such as neurodegenerative diseases.
Claims59
A polypeptide comprising an amino acid sequence having at least 70% identity to the sequence DGIWKASFTTFTVTKYWFYR or VTKYWFYR, wherein said polypeptide is less than 170 amino acids in length.
A polypeptide comprising:
- (a) an amino acid sequence having at least 70% identity to the sequence DGIWKASFTTFTVTKYWFYR or VTKYWFYR, and (b) a heterologous sequence.
A soluble polypeptide comprising a fragment of caveolin-1, wherein said fragment binds to a portion of P-glycoprotein.
A polypeptide comprising an amino acid sequence having at least 70% identity to the sequence VFSMFRYSNWLDK, wherein said polypeptide is less than 1000 amino acids in length.
A polypeptide comprising:
- (a) an amino acid sequence having at least 70% identity to the sequence VFSMFRYSNWLDK, and (b) a heterologous sequence.
A soluble polypeptide comprising a fragment of P-glycoprotein, wherein said fragment binds to a portion of caveolin-1.
The method of claim 58, wherein said neurodegenerative disease is Alzheimer's disease, Parkinson's disease, Huntington's disease, prion disease, bovine spongiform encephalopathy, Creutzfeldt-Jakob disease, amyotrophic lateral sclerosis, Lewy body disease, or Pick's disease.
Dependencies are inferred from the claim text.