ST receptor binding compounds and methods of using the same

• US 20060269477A1
• Filed: 07/28/2006
• Published: 11/30/2006
• Est. Priority Date: 10/26/1993
• Status: Abandoned Application

• Current Assignee: Thomas Jefferson University (Main Line Health System)
• Original Assignee: Thomas Jefferson University (Main Line Health System)
• Inventors: Waldman, Scott A.
• Application Number:
  US11/494,901
• Publication Number:
  US 20060269477A1
• Time in Patent Office: Days
• US Class Current: 424/1.110
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/6425 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
• CPC Class Codes: A61K 51/08 Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins
• CPC Class Codes: C07K 14/24 from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Conjugated compounds which comprises an ST receptor binding moiety and a radiostable active moiety are disclosed. Pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent, and a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radioactive active moiety are disclosed. Methods of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent, and a therapeutically effective amount of a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radiostable active moiety are disclosed. Methods of radioimaging metastasized colorectal cancer cells comprising the steps of first administering to an individual suspected of having metastasized colorectal cancer cells, a pharmaceutical composition that comprises a pharmaceutically acceptable carrier or diluent, and conjugated compound that comprises an ST receptor binding moiety and a radioactive active moiety wherein the conjugated compound is present in an amount effective for diagnostic use in humans suffering from colorectal cancer and then detecting the localization and accumulation of radioactivity in the individual'"'"'s body are disclosed.

Claims

1. A conjugated compound comprising:

a) a ST receptor binding moiety; and

b) an active moiety;

wherein said active moiety is a radiostable active agent.

2. The compound of claim 1 wherein said ST receptor binding moiety is a peptide.

3. The compound of claim 1 wherein said ST receptor binding moiety is selected from the group consisting of:

SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NOS;

5-54 and fragments and derivatives thereof.

4. The compound of claim 1 wherein said ST receptor binding moiety is selected from the group consisting of SEQ ID:

2, SEQ ID NO;

3, SEQ ID NO;

5, SEQ ID NO;

6 and SEQ ID NO;

54.

5. The compound of claim 1 wherein said active moiety is a therapeutic agent.

6. The compound of claim 1 wherein said active moiety is selected from the group consisting of:

methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cis-platin, vindesine, mitomycin, bleomycin, purothionin, macromomycin, 1,4-benzoquinone derivatives, trenimon, ricin, ricin A chain, Pseudomonas exotoxin, diphtheria toxin, Clostridium perfringens phospholipases C, bovine pancreatic ribonuclease, pokeweek antiviral protein, abrin, abrin A chain, cobra venom factor, gelonin, saporin, modeccin, viscumin, volkensin, alkaline phosphatase, nitroimidazole, metronidazole and misonidazole.

7. The compound of claim 1 wherein:

a) said ST receptor binding moiety is selected from the group consisting of;

SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NOS;

5-54 and fragments and derivatives thereof;

b) said an active moiety is selected from the group consisting of;

methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cis-platin, vindesine, mitomycin, bleomycin, purothionin, macromomycin, 1,4-benzoquinone derivatives, trenimon, ricin, ricin A chain, Pseudomonas exotoxin, diphtheria toxin, Clostridium perfringens phospholipases C, bovine pancreatic ribonuclease, pokeweed antiviral protein, abrin, abrin A chain, cobra venom factor, gelonin, saporin, modeccin, viscumin, volkensin, alkaline phosphatase, nitroimidazole, metronidazole and misonidazole.

8. The compound of claim 1 wherein said an active moiety is selected from the group consisting of:

methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, cis-platin, vindesine, mitomycin and bleomycin, alkaline phosphatase, ricin A chain, Pseudomonas exotoxin and diphtheria toxin.

9. The compound of claim 1 wherein:

a) said ST receptor binding moiety is selected from the group consisting of;

SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

5, SEQ ID NO;

6 and SEQ ID NO;

54; and

b) said an active moiety is selected from the group consisting of;

methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, cis-platin, vindesine, mitomycin and bleomycin, alkaline phosphatase, ricin A chain, Pseudomonas exotoxin and diphtheria toxin.

10. A pharmaceutical composition comprising:

a) a pharmaceutically acceptable carrier or diluent, and

b) a conjugate compound according to claim 1.

11. A method of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition according to claim 10.

25. The compound of claim 1 wherein said active moiety is an enzyme.

26. The compound of claim 25 wherein said active moiety is alkaline phosphatase.

12. A pharmaceutical composition comprising:

a) a pharmaceutically acceptable carrier or diluent, and,

b) conjugated compound comprising;

i) a ST receptor binding moiety; and

ii) an active moiety wherein said active moiety is a radioactive agent and said conjugated compound is present in an amount effective for therapeutic or diagnostic use in humans suffering from colorectal cancer.

13. The pharmaceutical composition of claim 12 wherein said active moiety is selected from the group consisting of:

⁴⁷Sc, ⁶⁷Cu, ⁹⁰Y, ¹⁰⁹Pd, ¹²³I, ¹²⁵I, ¹³¹I, ¹⁸⁶Re, ¹⁹⁹Au, ²¹¹At, ²¹²Pb, ²¹²B, ³²P, ³³P, ⁷⁷Ge, ⁷⁷As, ¹⁰³Pb, ¹⁰⁵Rh, ¹¹¹Ag, ¹¹⁹Sb, ¹²¹Sn, ¹³¹Cs, ¹⁴³Pr, ¹⁶¹Tb, ¹⁷⁷Lu, ¹⁹¹Os, ^193MPt and ¹⁹⁷Hg.

14. The pharmaceutical composition of claim 12 wherein said active moiety is selected from the group consisting of:

⁴³K, ⁵²Fe, ⁵⁷Co, ⁶⁷Cu, ⁶⁷Ga, ⁶⁸Ga, ⁷⁷Br, ⁸¹Rb/^81MKr, ^87MSr, ^99MTc, ¹¹¹In, ¹¹³In, ¹²³I, ¹²⁵I, ¹²⁷Cs, ¹²⁹Cs, ¹³¹I, ¹³²I, ¹⁹⁷Hg, ²⁰³Pb and ²⁰⁶Bi.

15. The pharmaceutical composition of claim 12 wherein said ST receptor binding moiety is a peptide.

16. The pharmaceutical composition of claim 12 wherein said ST receptor binding moiety is selected from the group consisting of:

SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NOS;

5-54 and fragments and derivatives thereof.

17. The pharmaceutical composition of claim 12 wherein said ST receptor binding moiety is selected from the group consisting of SEQ ID NO:

2, SEQ ID NO;

3, SEQ ID NO;

5, SEQ ID NO;

6 and SEQ ID NO;

54.

18. The pharmaceutical composition of claim 12 wherein said ST receptor binding moiety is selected from the group consisting of:

SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

5, SEQ ID NO;

6 and SEQ ID NO;

54, and said active moiety is selected from the group consisting of;

⁴⁷Sc, ⁶⁷Cu, ⁹⁰Y, ¹⁰⁹Pd, ¹²³I, ¹²⁵I, ¹³¹I, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁹⁹Au, ²¹¹At, ²¹²Pb, ²¹²B, ³²P and ³³P, ⁷¹Ge, ⁷⁷As, ¹⁰³Pb, ¹⁰⁵Rh, ¹¹¹Ag, ¹¹⁹Sb, ¹²¹Sn, ¹³¹Cs, ¹⁴³Pr, ¹⁶¹Tb, ¹⁷⁷Lu, ¹⁹¹Os, ^193MPt and ¹⁹⁷Hg.

19. The pharmaceutical composition of claim 12 wherein said ST receptor binding moiety is selected from the group consisting of:

SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO.5, SEQ ID NO;

6 and SEQ ID NO;

54, and said active moiety is selected from the group consisting of ⁴³K, ⁵³Fe, ⁵⁷Co, ⁶⁷Cu, ⁶⁷Ga, ⁶⁸Ga, ⁷⁷Br, ⁸¹Rb/^81MKr, ^87MSr, ^99MTc, ¹¹¹In, ¹²³I, ¹²⁵I, ¹²⁷Cs, ¹²⁹Cs, ¹³¹I, ¹³²I, ¹⁹⁷Hg, ²⁰³Pb and ²⁰⁶Bi.

20. A method of radioimaging metastasized colorectal cancer cells comprising the steps of administering to an individual a pharmaceutical composition comprising:

a) a pharmaceutically acceptable carrier or diluent, and

b) conjugated compound comprising;

i) a ST receptor binding moiety; and

ii) an active moiety;

wherein said active moiety is a radioactive agent and said conjugated compound is present in an amount effective for diagnostic use in humans suffering from colorectal cancer.

21. A method of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition comprising:

a) a pharmaceutically acceptable carrier or diluent, and,

b) conjugated compound comprising;

i) a ST receptor binding moiety; and

ii) an active moiety;

wherein said active moiety is a radiostable agent or radioactive agent and said conjugated compound is present in an amount effective for therapeutic or diagnostic use in humans suffering from colorectal cancer.

22. A method of delivery of a nucleic acid molecule to intestinal tract cells of an individual comprising the steps of administering to said individual a pharmaceutical composition comprising:

a) a pharmaceutically acceptable carrier or diluent, and,

b) a composition comprising;

i) a ST receptor ligand; and

ii) a nucleic acid molecule.

23. A method of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual:

a) a conjugated compound comprising an ST receptor binding moiety and an enzyme; and

b) a prodrug which when processed by the enzyme is converted to a drug.

24. The method of claims 23 wherein:

a) a conjugated compound comprises an ST receptor binding moiety and alkaline phosphatase; and

b) the prodrug is etoposidephosphate.