Peptides and peptidomimetics having anti-proliferative activity and/or that augment nucleic acid damaging agents or treatments

• US 7,476,657 B2
• Filed: 09/06/2005
• Issued: 01/13/2009
• Est. Priority Date: 01/17/2002
• Status: Expired due to Term

• Current Assignee: CanBas Co., Ltd.
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Kobayashi, Hidetaka, Kawabe, Takumi
• Primary Examiner(s): Kosar; Andrew D
• Application Number:
  US11/221,348
• Publication Number:
  US 20060084610A1
• Time in Patent Office: 1,225 Days
• Field of Search: None
• US Class Current: 514/1.1
• 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 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 5/06078 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/06191 containing heteroatoms different from O, S, or N
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells. While the invention is not limited to any particular mechanism, the compounds of the invention appear to function at least in part by inhibiting G2 cell cycle checkpoint. Thus, invention compounds can be used to inhibit cell growth alone or be used in combination with a nucleic acid damaging treatment to inhibit cell growth.

Claims

1. A peptide selected from the group consisting of

(d-Bpa)(d-Ser)(d-Trp)(d-Ser)(d-Bpa)(d-Cha)(d-Arg)(d-Arg)(d-Arg)(d-Gln)(d-Arg) (d-Arg)(SEQ ID NO:

130)(CBP601); and

(d-Bpa)(d-Ser)(d-Trp)(d-Ser)(d-Phe-4-NO₂)(d-Cha)(d-Arg)(d-Arg)(d-Arg)(d-Gln)(d-Arg)(d-Arg)(SEQ ID NO;

89)(CBP603).

2. The peptide of claim 1 wherein the peptide is (d-Bpa)(d-Ser) (d-Trp)(d-Ser)(d-Phe-4-NO₂)(d-Cha)(d-Arg)(d-Arg)(d-Arg)(d-Gln)(d-Arg)(d-Arg) (SEQ ID NO:

89)(CBP603).

3. The peptide of claim 1, wherein the sequence inhibits proliferation of a cell.

4. The peptide of claim 1, wherein the sequence abrogates cell cycle G2 checkpoint of a cell.

5. A composition comprising the peptide of claim 1, and a nucleic acid damaging agent.

6. A composition comprising the peptide of claim 1, and an anti-proliferative agent.

7. A pharmaceutical composition comprising the peptide of claim 1.

8. A pharmaceutical composition comprising the peptide of claim 1 and a nucleic acid damaging agent or an anti-proliferative agent.

9. A kit comprising the peptide of claim 1 and instructions for use.

10. The kit of claim 9, wherein the instructions for use include instructions for inhibiting cell proliferation in combination with a nucleic acid damaging treatment.

11. The kit of claim 9, further comprising a nucleic acid damaging agent.

12. The kit of claim 9, further comprising an anti-proliferative agent.