Compounds

1. A compound, or pharmaceutically acceptable salt thereof, comprising a vascular disrupting agent (VDA) associated with a matrix metalloproteinase (MMP) proteolytic cleavage site, wherein the VDA is selected from the group consisting of azademethylcolchicine, colchicine, azacolchicine, N-methyl desacetylcolchicine, desacetylcolchicine, N-acetylcolchinol-O-phosphate, colchicinoids, combrestatins, phenstatin, podophyllotoxins, steganacins, amphethinile, stilbenes, flavonoids, vincristine, vinblastine, vinflunine, maytansinoids, phomopson A, rhizoxin, auristatin, and dolstatin, and the MMP proteolytic cleavage site comprises the amino acid sequence eu-P2′-Hof-Gly-Cit-Ser-Arg, wherein P2′ is an amino acid selected from Asp, Ala, Ser, Asn, Pro, Leu, Arg and Thr.

2. The compound according to claim 1 wherein the compound is of formula (I)

X—Y  (I)

wherein

X is the VDA; and

Y is the peptide comprising the MMP proteolytic cleavage site.

3. The compound according to claim 1 wherein the VDA is selected from azademethylcolchicine, colchicine, azacolchicine, N-methyl desacetylcolchicine, desacetylcolchicine.

4. The compound according to claim 2 wherein Y is a peptide sequence of between seven and ten amino acids.

5. The compound according to claim 1 wherein the amino acid at P2′ is methylated.

6. The compound according to claim 2 wherein the compound is of formula (II)

X—Y- c   (II)

wherein c is a capping group which prevents non-specific degradation of the peptide by enzymes other than MMPs.

7. The compound according to claim 6 wherein c is selected from the group consisting of fluorescein isothiocyanate and fluorescein.

8. The compound according to claim 6 wherein c is the formula (c) n and wherein n is an integer between 1 and 5.

9. The compound according to claim 8 wherein c is a non-natural amino acid and n is 3.

10. The compound according to claim 2 wherein the compound is of formula (III)

X- a -Y  (III)

wherein a is a linker directly or indirectly associated with X and wherein the linker is a single amino acid or amino acid sequence.

11. The compound according to claim 10 wherein the compound is of formula (IV)

X- a -Y- c   (IV)

wherein c is a capping group which prevents non-specific degradation of the peptide by enzymes other than MMPs.

12. The compound according to claim 6 wherein the compound is of formula (V)

X—Y- b - c   (V)

wherein b is a spacer group directly or indirectly linked to Y and wherein the spacer is selected from the group consisting of a single amino acid, amino acid sequence and a succinyl group.

13. The compound according to claim 11 wherein the compound is of formula (VI)

X- a -Y- b - c   (VI)

wherein b is a spacer group directly or indirectly linked to Y and wherein the spacer is selected from the group consisting of a single amino acid, amino acid sequence and a succinyl group.

14. The compound as claimed in claim 2 wherein the compound is of formula (VII)

X—Y—Z  (VII)

wherein Z is an anti-cancer agent selected from the group consisting of a VDA, an antimetabolite and a cytotoxic agent,

wherein

the VDA is selected from the group consisting of azademethylcolchicine, colchicine, azacolchicine, N-methyl desacetylcolchicine, desacetylcolchicine, N-acetylcolchinol-O phosphate, colchicinoids, combrestatins, phenstatin, podophyllotoxins, steganacins, amphethinile, stilbenes, flavonoids, vincristine, vinblastine, vinflunine, maytansinoids, phomopson A, rhizoxin, auristatin, and dolstatin,

the antimetabolite is 5-fluorouracil, and

the cytotoxic agent is selected from the group consisting of anthracycline and doxorubicin.

15. The compound according to claim 14 wherein Z is doxorubicin.

16. The compound according to claim 14 wherein X is selected from azademethylcolchicine, colchicine, azacolchicine, N-methyl desacetylcolchicine, desacetylcolchicine.

17. The compound according to claim 14 wherein X and Z are selected from azademethylcolchicine, colchicine, azacolchicine, N-methyl desacetylcolchicine, desacetylcolchicine.

18. A pharmaceutical formulation comprising a compound according to claim 1 and at least one additional pharmaceutically acceptable excipient, diluent or carrier.

19. The compound according to claim 3 , wherein the VDA is azademethylcolchicine.

20. The compound according to claim 1 , wherein a further anti-cancer agent is linked to the peptide comprising the MMP proteolytic cleavage site.

21. The compound according to claim 20 , wherein the anti-cancer agent is selected from the group consisting of 5-fluorouracil, anthracycline, doxorubicin, vinca alkaloid, taxane, a cytotoxic nucleotide, a biotoxin, radiotherapeutic, hormonal agent, colchicine, azademethylcolchicine, N-methyl desacetylcolchicine or desacetylcolchicine.

22. The compound according to claim 21 , wherein the anti-cancer agent is doxorubicin.

23. The compound according to claim 1 further comprising a capping group on the peptide comprising the MMP proteolytic cleavage site which prevents non-specific degradation of the peptide.

24. A pharmaceutical formulation comprising the compound according to claim 1 and another therapeutic agent wherein the another therapeutic agent is selected from the group consisting of cisplatin, carboplatin, cyclophosphamide, melphalan, carmustine, methotrexate, 5-fluorouracil, cytarabine, mercatopurine, daunorubicin, doxorubicin, epirubicin, vinblastine, vincristine, dactinomycin, mitomycin C, taxol, L-asparaginase, granulocyte colony stimulating factor (G-CSF), etoposide, colchicine, deferoxamine mesylate and camptothecin.