Compounds containing a vascular disrupting agent
AssigneeIncanthera Ltd
InventorsJason Gill, Paul Loadman, Rob Falconer, Laurence Patterson, Jennifer Xavier, Michael Bibby
Life of this patent
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Abstract
The present invention relates to compounds, and pharmaceutically acceptable salts thereof, comprising a vascular disrupting agent (VDA) associated and a MMP proteolytic cleavage site. The compounds are useful in the treatment of cancer.
Claims18
A peptide comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4).
A prodrug comprising
- a biologically active compound associated with
- a peptide comprising a MMP proteolytic cleavage site comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4).
A compound of
- X-Y-c, or formula (II):
- X-a-Y-c, or formula (IV):
- X-Y-b-c, or formula (V):
- X-a-Y-b-c, formula (VI):
- wherein
- Y is a peptide comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4),
- c is a capping group,
- a is a linker,
- b is a spacer, and
- X is an anticancer agent.
A method of producing a systemically deactivated and MMP overexpression site activatable medicament, the method comprising attaching a peptide comprising an MMP proteolytic cleavage site comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4) to the medicament.
A method of modifying a drug to overcome a toxic effect of systemic administration of the drug, comprising associating the drug with a peptide comprising a MMP proteolytic cleavage site -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4) and having a capping group c on the N- or C-terminus to prevent non-specific degradation of the peptide.
A method of increasing the therapeutic index of a drug, the method comprising associating the drug with a peptide comprising -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4) and having a capping group c on the N- or C-terminus, thereby reducing systemic levels of active drug and increasing the therapeutic index.
A method of modifying a drug, the method comprising associating the drug with a peptide comprising a MMP proteolytic cleavage site -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4) and having a capping group c on the N- or C-terminus to prevent non-specific degradation of the peptide.
Dependencies are inferred from the claim text.