Peptides useable for treating cancer
Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH 2 —SO 3 H)COOH or Arg-Gly-NH—CH(CH 2 —SO 3 H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting integrins including but not necessarily limited to α 5 β 1 -Integrin, α v β 3 -Integrin and α v β 5 -Integrin, inhibiting cellular adhesion to RGD binding sites, preventing or treating viral or other microbial infections, inhibiting angiogenesis in tumors, retinal tissue or other tissues or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.
1. A method for treating a tumor in a human or animal subject in need thereof, said method comprising:
administering to the subject an effective amount of a peptide which comprises either:
i) Glycinyl-Arginyl-Glycinyl-Cysteic-Threonyl-Proline-COOH (SEQ ID NO: 2), or
ii) a peptide having the formula (SEQ ID NO: 9):
X 1 —R-G-Cysteic Acid-X
where X and X 1 are selected from: Phe-Val-Ala, -Phe-Leu-Ala, -Phe-Val-Gly, -Phe-Leu-Gly, -Phe-Pro-Gly, -Phe-Pro-Ala, -Phe-Val; or from Arg, Gly, Cysteic, Phe, Val, Ala, Leu, Pro, Thr and salts thereof and any combinations of D-isomers and L-isomers thereof.
2. A method according to claim 1 wherein method is carried out to treat a vascularized solid tumor.
3. A method according to claim 1 wherein the method is carried out to deter metastasis of a vascularized solid tumor.
4. A method according to claim 1 wherein the peptide has the formula (SEQ ID NO: 2):
5. A method according to claim 1 wherein the peptide is multimeric.
6. A method according to claim 5 wherein the multimeric peptide is bound to an antitumor substance.
7. A method according to claim 6 wherein the multimeric peptide comprises a multimeric form of Glycinyl-Arginyl-Glycinyl-Cysteic-Threonyl-Proline-COOH (SEQ ID NO: 2) having the formula:
8. A method according to claim 6 wherein the antitumor substance is selected from the group consisting of: cancer chemotherapeutic agents, biological response modifiers, vascularization inhibitors, hormone receptor blockers, cryotherapeutic agents; agents that destroy or inhibit neoplasia or tumorigenesis; alkylating agents; agents which directly kill cancer cells by attacking their DNA; cyclophosphamide; isophosphamide; nitrosoureas, agents which kill cancer cells by inhibiting changes necessary for cellular DNA repair; carmustine (BCNU); lomustine (CCNU); antimetabolites; agents that block cancer cell growth by interfering with DNA synthesis; 6 mercaptopurine; 5-fluorouracil (5FU); antitumor antibiotics; compounds that act by binding or intercalating DNA and preventing RNA synthesis; doxorubicin; daunorubicin; epirubicin; idarubicin; mitomycin-C; bleomycin; Vinca alkaloids; vincristine; vinblastine; steroid hormones; hormone inhibitors; hormone receptor antagonists; agents which affect the growth of hormone-responsive cancers; tamoxifen; herceptin; aromatase inhibitors; aminoglutethamide; formestane; triazole inhibitors; letrozole; anastrazole; steroidal inhibitors; exemestane; anti-angiogenic proteins; gene therapy agents; agents that inhibit angiogenesis or vascularization of tumors; meth-1; meth-2; thalidomide; bevacizumab (Avastin); squalamine; endostatin; angiostatin; Angiozyme; AE-941 (Neovastat); CC-5013 (Revimid); medi-522 (Vitaxin); 2-methoxyestradiol (2ME2, Panzem); carboxyamidotriazole (CAI); combretastatin A4 prodrug (CA4P); SU6668; SU11248; BMS-275291; COL-3; EMD 121974; IMC-1C11; IM862; TNP-470; celecoxib (Celebrex); rofecoxib (Vioxx); interferon alpha; interleukin-12 (IL-12); biological response modifiers; bacillus calmette-guerin (BCG); monoclonal antibodies; interluken 2, granulocyte colony stimulating factor (GCSF); PGDF receptor antagonists; herceptin; asparaginase; busulphan; carboplatin; cisplatin; carmustine; cchlorambucil; cytarabine; dacarbazine; etoposide; flucarbazine; flurouracil; gemcitabine; hydroxyurea; ifosphamide; irinotecan; lomustine; melphalan; mercaptopurine; methotrexate; thioguanine; thiotepa; tomudex; topotecan; treosulfan; vinblastine; vincristine; mitoazitrone; oxaliplatin; procarbazine; streptocin; taxol and taxotere.