Treatment of cancer with peptide analog of bombesin, GRP, litorin or neuromedin

A method of treating colon, prostate or breast cancer in a mammal by administering to said mammal an effective amount of a peptide, wherein said analog administered according to methods of the invention comprises a peptide comprising between seven and ten amino acid residues, inclusive, and is an analog of one of the following naturally occurring peptides terminating at the carboxy-terminus with a Met residue:

• (a) litorin;
• (b) the ten amino acid carboxy-terminal region of mammalian GRP, neuromedin B, or neuromedin C;
• and (c) the ten amino acid carboxy-terminal region of amphibian bombesin, said analog being of the following formula:
• ##STR20## wherein A.sup.0 =pGlu, Gly, Nle, .alpha.-aminobutyric acid, or the D-isomer of any of Ala, Val, Gln, Asn, Leu, Ile, Met, p-X-Phe (where X=F, Cl, Br, NO.sub.2, OH, H or CH.sub.3), Trp, Cys, or .beta.-Nal, or is deleted;
• A.sup.1 =the D or L-isomer of any of pGlu, Nle, .alpha.-aminobutyric acid, or the D-isomer of any of Ala, Val, Gln, Asn, Leu, Ile, Met, p-X-Phe (where X=F, Cl, Br, NO.sub.2, OH, H or CH.sub.3), F.sub.5 -Phe, Trp, Cys, or .beta.-Nal, or is deleted;
• A.sup.2 =pGlu, Gly, Ala, Val, Gln, Asn, Leu, Ile, Met, p-X-Phe (where X=F, Cl, Br, NO.sub.2, OH, H or CH.sub.3), Trp, Cys, .beta.-Nal, His, 1-methyl-His, or 3-methyl-His;
• A.sup.4 =Ala, Val, Gln, Asn, Gly, Leu, Ile, Nle, .alpha.-aminobutyric acid, Met, p-X-Phe (where X=F, Cl, Br, NO.sub.2, OH, H or CH.sub.3), Trp, Cys, or .beta.-Nal;
• A.sup.5 =Gln, Asn, Gly, Ala, Leu, Ile, Nle, .alpha.-aminobutyric acid, Met, Val, p-X-Phe (where X=F, Cl, Br, OH, H or CH.sub.3), Trp, Thr, or .beta.-Nal;
• A.sup.6 =Sar, Gly, or the D-isomer of any of Ala, N-methyl-Ala, Val, Gln, Asn, Leu, Ile, Met, p-X-Phe (where X=F, Cl, Br, NO.sub.2, OH, H or CH.sub.3), Trp, Cys, or .beta.-Nal;
• A.sup.7 =1-methyl-His, 3-methyl-His, or His;
• provided that, if A.sup.0 is present, A.sup.1 cannot be pGlu;
• further provided that, if A.sup.0 or A.sup.1 is present, A.sup.2 cannot be pGlu;
• further provided that, when A.sup.0 is deleted and A.sup.1 is pGlu, R.sub.1 must be H and R.sub.2 must be the portion of Glu that forms the imine ring in pGlu;
• and further provided that, W can be any one of the following:
• ##STR21## wherein R.sub.3 is CHR.sub.20 --(CH.sub.2).sub.n1 (where R.sub.20 is either of H or OH;
• and n1 is either of 1 or 0), or is deleted, and Z.sub.1 is the identifying group of any of the amino acids Gly, Ala, Val, Leu, Ile, Ser, Asp, Asn, Glu, Gln, p-X-Phe (where X=H, F, Cl, Br, NO.sub.2, OH, or CH.sub.3), F.sub.5 -Phe, Trp, Cys, Met, Pro, HyPro, cyclohexyl-Ala, or .beta.-nal, and V is either ##STR22## where R.sub.4 is any of C.sub.1-20 alkyl, C.sub.3-20 alkenyl, C.sub.3-20 alkynyl, phenyl, naphthyl, or C.sub.7-10 phenylalkyl, and each R.sub.5, and R.sub.6, independently, is any of H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, lower acyl, or, ##STR23## where R.sub.22 is any of H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, or lower acyl;
• provided that, when one of R.sub.5 or R.sub.6 is --NHR.sub.22, the other is H;
• ##STR24## wherein R.sub.4 is CH.sub.2 --NH, CH.sub.2 --S, CH.sub.2 --O, CO--CH.sub.2, CH.sub.2 --CO, or CH.sub.2 --CH.sub.2, and each Z.sub.1 and Z.sub.2, independently, is the identifying group of any one of the amino acids Gly, Ala, Val, Leu, Ile, Ser, Asp, Asn, Glu, Gln, .beta.-Nal, p-X-Phe (where X=H, F, Cl, Br, NO.sub.2, OH or CH.sub.3), F.sub.5 -Phe, Trp, Cys, Met, Pro, HyPro, or cyclohexyl-Ala;
• and V is either OR.sub.5 or ##STR25## where each R.sub.3, R.sub.5, R.sub.6, and R.sub.7, independently, is H, lower alkyl, lower phenylalkyl, or lower naphthylalkyl;
• ##STR26## wherein Z.sub.1 is the identifying group of any one of the amino acids Gly, Ala, Val, Leu, Ile, Ser, Asp, Asn, Glu, .beta.-Nal, Gln, p-X-Phe (where X=H, F, Cl, Br, NO.sub.2, OH or CH.sub.3), F.sub.5 -Phe, Trp, Cys, Met, Pro, or HyPro;
• and each Z.sub.2, Z.sub.3, and Z.sub.4, independently, is H, lower alkyl, lower phenylalkyl, or lower naphthylalkyl;
• or ##STR27## wherein each Z.sub.20 and Z.sub.30, independently, is H, lower alkyl, lower phenylalkyl, lower naphthylalkyl;
• further provided that, when either of Z.sub.20 or Z.sub.30 is other than H, A.sup.7 is His, A.sup.6 is Gly, A.sup.5 is Val, A.sup.4 is Ala, A.sup.2 is His, and either of R.sub.1 or R.sub.2 is other than H, A.sup.1 must be other than deleted;
• further provided that, for the formulas (I) through (IV), any asymmetric carbon atom can be R, S or a racemic mixture;
• and further provided that each R.sub.1 and R.sub.2, independently, is H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, COE.sub.1 (where E.sub.1 is C.sub.1-20 alkyl, C.sub.3-20 alkenyl, C.sub.3-20 alkynyl, phenyl, naphthyl, or C.sub.7-10 phenylalkyl), or lower acyl, and R.sub.1 and R.sub.2 are bonded to the N-terminal amino acid of said peptide, and further provided that when one of R.sub.1 or R.sub.2 is COE.sub.1, the other must be H, or a pharmaceutically acceptable salt thereof.