Targeted delivery to legumain-expressing cells
AssigneeThe Scripps Research Institute
InventorsCheng Liu, Thomas Edgington
Life of this patent
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Abstract
The present invention relates to new agents and methods useful for preventing, treating and diagnosing diseases such as cancer. For example, the invention relates to prodrug agents useful for targeting and delivering cytotoxic drugs to cancerous cells.
Claims52
A prodrug compound, comprising a drug molecule linked to a legumain peptide substrate, wherein the peptide has an amino acid sequence comprising at least two linked amino acids, wherein at least one of the two linked amino acids is Asn, and wherein legumain cleaves the peptide at the link between the Asn and another amino acid to generate an active drug from the prodrug.
A compound comprising a legumain inhibitor of including formula III or IV:
- Pr-(Xaa4)n-Asn-CHO III
- Xaa4-Asn-Y IV
- wherein:
- Pr is a protecting group;
- n is an integer of about 2 to about 5;
- Xaa4 is an amino acid or an amino acid mimetic;
- Y is alkyl or alkenyl, optionally substituted with 1-3 halo or hydroxy, alkylamino, dialkylamino, alkyldialkylamino, or cycloalkyl, alkylcycloalkyl, alkenylcycloalkyl, aryl;
- (C5-C12)arylalkyl or (C5-C12)arylalkenyl,
- wherein the aryl groups of the arylalky or arylalkenyl comprises 0-4 heteroatoms selected from N, O and S, and are optionally substituted with halo, cyano, nitro, haloalkyl, amino, aminoalkyl, dialkylamino, alkyl, alkenyl, alkynyl, alkoxy, haloalkoxy, carboxyl, carboalkoxy, alkylcarboxamide, (C5-C6)aryl, —O—(C5-C6)aryl, arylcarboxamide, alkylthio or haloalkylthio;
- and
- wherein the inhibitor is capable of binding to legumain.
A method for imaging a tissue, comprising contacting a test tissue suspected of comprising legumain with of an agent that specifically binds to legumain, and detecting whether the agent binds to the test tissue.
A method for diagnosing cancer in a tissue, comprising contacting the tissue with of an agent that specifically binds to legumain, and detecting whether the agent binds to the tissue.
A method for diagnosing cancer in an animal, comprising administering to the animal an agent that specifically binds to legumain, and detecting whether the agent accumulates in a tissue.
A method for treating cancer or cancer cell migration in animal, comprising administering to the animal a compound that inhibits legumain in amounts and at intervals effective to prevent, reduce, or eliminate one or more symptoms of cancer in the animal.
A method for treating inflammation in an animal, comprising administering to the mammal a compound that inhibits legumain in amounts and at intervals effective to prevent, reduce, or eliminate one or more symptoms associated with inflammation.
A method for delivering a drug to a legumain-expressing cell in a mammal, which comprises administering to the mammal an effective amount of a drug attached an agent that binds to legumain, wherein the agent that binds to legumain is a compound that inhibits legumain, a legumain substrate, or an anti-legumain antibody.
Dependencies are inferred from the claim text.