Compounds
AssigneeIncanthera Ltd
InventorsJason Gill, Paul Loadman, Rob Falconer, Lawrence Patterson, Jennifer Atkinson, Michael Bibby
Life of this patent
Estimating the term…
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.
Claims28
A pharmaceutical formulation comprising
- (a) a compound, or pharmaceutically acceptable salt thereof, comprising a vascular disrupting agent (VDA) selected from the group consisting of colchicine, azademethylcolchicine, azacolchicine, N-methyl desacetylcolchicine and desacetylcolchicine, wherein the compound is linked to a peptide comprising a matrix metalloproteinase (MMP) proteolytic cleavage site comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu-(SEQ ID NO:4),
- (b) another therapeutic agent, and
- (c) at least one pharmaceutically acceptable excipient, diluent or carrier.
A method of treating a disease or condition associated with tissue expressing an MMP in a subject comprising administering to the subject an effective amount of a compound comprising a vascular disrupting agent (VDA) selected from the group consisting of colchicine, azademethylcolchicine, azacolchicine, N-methyl desacetylcolchicine and desacetylcolchicine, wherein the compound is linked to a peptide comprising a matrix metalloproteinase (MMP) proteolytic cleavage site comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:4) or a pharmaceutically acceptable salt thereof.
A compound, or pharmaceutically acceptable salt thereof, comprising a vascular disrupting agent (VDA), wherein the VDA is an anti-cancer agent, linked to 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 peptide comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:
- 4), wherein the amino acid sequence is an MMP-14 specific cleavage site.
A method of producing a systemically deactivated and MMP overexpression site activatable medicament, the method comprising attaching 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 overcoming toxic effect of systemic administration of an anti-cancer agent, the method comprising administering the anti-cancer agent attached to a peptide comprising -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:4) to a subject in need thereof.
A prodrug comprising a MMP proteolytic cleavage site comprising the amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu- (SEQ ID NO:4).
A compound, or pharmaceutically acceptable salt thereof, of formula comprising X—Y
- wherein X is a vascular disrupting agent (VDA);
- and Y is a peptide sequence comprising a matrix metalloproteinase (MMP) proteolytic cleavage site comprising the formula P4-P3-P2-P1-P1′-P2′-P3′-P4′ wherein P1 to P4 and P1′ to P4′ are amino acids and may be the same or different and wherein proteolytic cleavage takes place between residues P1 and P1′.
Dependencies are inferred from the claim text.