WO2007124284B1 - Bombesin receptor anatogonists with anti-cancer activity - Google Patents
Bombesin receptor anatogonists with anti-cancer activityInfo
- Publication number
- WO2007124284B1 WO2007124284B1 PCT/US2007/066615 US2007066615W WO2007124284B1 WO 2007124284 B1 WO2007124284 B1 WO 2007124284B1 US 2007066615 W US2007066615 W US 2007066615W WO 2007124284 B1 WO2007124284 B1 WO 2007124284B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antagonist
- seq
- cell
- neoplastic cell
- peptide
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
- C07K7/086—Bombesin; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Synthetic peptides that inhibit ligand-binding by bombesin receptors are provided. Methods for inhibiting growth and inducing apoptosis of neoplastic cells using these peptides are also provided. Methods for treating cancer by administering the peptides are also provided.
Claims
1. A bombesin receptor antagonist comprising at least 6 contiguous amino acids of YFVLISVFILSPlYVYSFYIA (Peptide X; SEQ ID NO: 2), wherein the antagonist targets the fifth transmembrane domain of the bombesin receptor.
2. The antagonist of claim I , wherein antagonist competitively inhibits binding of methadone to the bombesin receptor.
3. The antagonist of claim 1, wherein the antagonist specifically binds to an amino acid sequence consisting of SFLVFYVIPLSIISVYYYFIA (Peptide O; SEQ TD NO:1) or fragments thereof.
4. The antagonist of claim 1, wherein the antagonist comprises at least 8 contiguous amino acids of YFVLISVFILSPIYVYSFYIA (Peptide X; SEQ ID NO:2).
5. The antagonist of claim 1, wherein the antagonist is selected from peptides that when aligned with SEQ ID NO:2 comprise; amino acids corresponding to positions 1-3, 7, 10-16, 18, 20 and 21 that are identical to SEQ ID NO:2; amino acids corresponding to positions 4 and 5 of SEQ ID NO:2 that are leucine or isoleucine; amino acids corresponding to position 6 of SEQ ID NO:2 is serine or isoleucine; amino acids corresponding to positions S and 9 of SEQ ID NQ:2 are phenylalanine or isoleucine; amino acid corresponding to position 17 of SEQ ID NO:2 is serine or phenylalanine; or amino acid corresponding to position 19 of SEQ ID NO:2 is tyrosine or valine.
6. The antagonist of claim 1 , wherein the peptide comprises a subsequence of SEQ ID NO:2 selected from YFVLISVF1L (SEQ ID NO:3), YFVILI (SEQ ID NO:4), SPIYV (SEQ ID NO:5), SFVIA (SEQ ID NO:6), SVIFL (SEQ ID NO:7), YFVYIA (SEQ ID NO:S), YSFY (SEQ ID NO.9), and SPIYVYSFYIA (SEQ ID NO:10).
7. The antagonist of claim 1, wherein the peptide comprises the sequence YFVLISVFILSPIYVYSFYTA (Peptide X; SEQ TD NO:2).
8. The antagonist of claim 1 , wherein the peptide consists of the sequence YFVLISVFILSPIYVYSFYIA (Peptide X; SEQ ID NO:2).
9. The antagonist of claim 1 , wherein the antagonist of the bombesin receptor suppresses growth of a cell contacted with the antagonist.
10. The antagonist of claim 9, wherein the antagonist suppresses growth by inducing apoptosis of the cell,
11. The antagonist of claim 9, wherein the cell over-expresses a bombesin receptor.
12. The antagonist of claim 11, wherein the cell that over-expresses the bombesin receptor is a neoplastic cell.
13. The antagonist of claim 9, wherein suppression of growth by the antagonist is resistant to inhibition by nicotine.
14. The antagonist of claim 1, wherein the antagonist is a peptide produced by solid phase synthesis.
15. The antagonist of claim 1, wherein the antagonist is a recombinant polypeptide or subsequence thereof.
16. The antagonist of claim 15, wherein the antagonist is a peptide produced by cleavage of a recombinant polypeptide,
17. A bombesin receptor antagonist, wherein the antagonist is an inhibitor of bombesin-receptor mediated neoplastic activity comprising at least one linear sequence of amino acids comprising at least 6 contiguous amino acids of YFVLTSVFILSPIYVYSFYIA (Peptide X; SEQ ID NO:2), wherein the at least one linear sequence of amino acids targets the fifth transmembrane domain of the bombesin receptor.
18. The antagonist of claim 17, wherein the antagonist suppresses growth of a neoplastic cell over-expressing a bombesin receptor when brought into contact with the neoplastic cell.
19. The antagonist of claim 18, wherein the antagonist induces apoptosis of the neoplastic cell, thereby suppressing growth of the neoplastic cell.
20. An anti-neoplastio agent comprising at least one linear sequence of amino acids comprising at least 6 contiguous amino acids of YFVLISVFILSPIYVYSFYIA (Peptide X; SEQ ID NO:2), wherein the at least one linear sequence of amino acids targets the fifth transmembrane domain of the bombesin receptor.
21. A pharmaceutical composition comprising the antagonist of any of claims 1 - 19, or the agent of claim 20, and a pharmaceutically acceptable carrier,
22. The pharmaceutical composition of claim 21 , wherein the composition comprises an aqueous formulation or an atomized freeze-dried formulation.
23. The pharmaceutical composition of claim 21, wherein the composition comprises an extended-release formulation.
24. The pharmaceutical composition of claim 23, wherein the extended-release formulation comprises a biodegradable microsphere or a water-in-oil-in-water double emulsion.
25. The pharmaceutical composition of claim 24, wherein the biodegradable microsphere comprises a; poly (lactide-co-glycolide) microsphere.
26. A method for suppressing growth of a neoplastic cell, the method comprising: contacting the neoplastic cell with the antagonist of any one of claims 1-19, the antineoplastic agent of claim 20 or the pharmaceutical composition of any one of claims 20-25, thereby suppressing growth of the neoplastic cell.
27. The method of claim 26, wherein the antagonist, antineoplastic agent and/or pharmaceutical composition suppresses growth by inducing apoptosis of the neoplastic cell.
28. The method of claim 26, wherein the neoplastic cell is a cell of a tumor.
29. The method of claim 26, wherein the neoplastic cell is a cancer cell.
30. The method of claim 29, wherein the cancer cell is a lung cancer cell, an osteosarcoma cell, a breast cancer cell, a colon cancer cell, a gastric cancer cell, a pancreatic cancer cell, a prostate cancer cell or a melanoma cell.
31. The method of claim 26, wherein the neoplastic cell over-expresses a bombesin receptor.
32. The method of claim 31, wherein the bombesin receptor is a gastrin releasing peptide receptor (GRP-R) or a neuromedin 13 receptor (NMB-R).
33. The method of claim 26, wherein the neoplastic cell further expresses at least one bombesin-like peptide (BLP).
34. The method of claim 26, wherein the neoplastic cell is contacted in vivo.
35. A method for treating a subject with a neoplasm, the method comprising: selecting a subject with at least one neoplastic cell; and contacting the at least one neoplastic cell with a composition comprising the antagonist of any one of claims 1-19, the antineoplastic agent of claim 20 or the pharmaceutical composition of any one of claims 20-25, which composition suppresses growth of the at least one neoplastic cell, thereby treating the subject with the neoplasm.
36. The method of claim 35, wherein the composition suppresses growth of the at least one neoplastic cell by inducing apoptosis of the at least one neoplastic cell.
37. The method of claim 35, wherein the neoplastic cell is a cancer cell.
38. The method of claim 35, wherein the neoplastic cell over-expresses a bombesin receptor.
39. The method of claim 35, wherein the neoplastic cell further expresses a bombesin-like peptide (BLP).
40. The method of claim 35, wherein the antagonist docs not appreciably affect a non-neoplastic cell.
41. The method of claim 35, wherein suppression of growth by the composition is resistant to inhibition by nicotine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79201106P | 2006-04-13 | 2006-04-13 | |
| US60/792,011 | 2006-04-13 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2007124284A2 WO2007124284A2 (en) | 2007-11-01 |
| WO2007124284A3 WO2007124284A3 (en) | 2008-02-28 |
| WO2007124284B1 true WO2007124284B1 (en) | 2008-05-08 |
Family
ID=38625704
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2007/066615 WO2007124284A2 (en) | 2006-04-13 | 2007-04-13 | Bombesin receptor anatogonists with anti-cancer activity |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2007124284A2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749596A (en) * | 2017-03-06 | 2017-05-31 | 天津医科大学 | Bombina orientalis biologically active peptide, gene and its application in pharmacy |
| CN109422810A (en) * | 2017-08-24 | 2019-03-05 | 孙立春 | The exploitation and application of full source of people or humanization bombesin receptor GRPR monoclonal antibody drug or diagnostic reagent |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5723578A (en) * | 1987-09-24 | 1998-03-03 | The Administrators Of Tulane Educational Fund | Peptide analogs of bombesin |
| US5620955A (en) * | 1993-06-18 | 1997-04-15 | Peptide Technologies Corporation | Bombesin receptor antagonists and uses thereof |
-
2007
- 2007-04-13 WO PCT/US2007/066615 patent/WO2007124284A2/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007124284A3 (en) | 2008-02-28 |
| WO2007124284A2 (en) | 2007-11-01 |
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