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US 5,620,955 AGranted
Bombesin receptor antagonists and uses thereof
AssigneePeptide Technologies Corporation
InventorsMartha Knight, Kazuyuki Takahashi, Bhaskar Chandrasekhar
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AssigneePeptide Technologies Corporation
InventorsMartha Knight, Kazuyuki Takahashi, Bhaskar Chandrasekhar
Estimating the term…
Bombesin is an amphibian peptide that has a structure closely related to that of several mammalian peptides, including Gastrin Releasing Peptide (GRP) and Neuromedins B and C. Bombesin, GRP and related peptides exert their in vivo effects by binding to specific receptors present on cells of the gastrointestinal tract, the central nervous system, and tumors. The invention relates to novel bombesin derivatives which act as bombesin receptor antagonists by blocking the binding of bombesin, GRP or related peptides to cellular receptors. By blocking the binding of bombesin, GRP and related peptides to cellular receptors on cancer cells, these antagonists inhibit the growth of tumor cells that respond to the growth-promoting action of bombesin. These antagonists are expected to block the binding of bombesin, GRP or related peptides to similar receptors on cells in the gastrointestinal tract or the central nervous system. Thus, these antagonists have therapeutic use in the treatment or prevention of conditions mediated by bombesin, GRP or related peptides, including cancer and gastrointestinal disorders such as peptic ulcer, pancreatitis, and feeding disorders.
A synthetic derivative of a peptide having
A bombesin receptor antagonist that is a peptide, wherein the carboxy-terminal residue of said peptide has an ethyl ester, and said peptide has the sequence R.sup.4 -His-Trp-Ala-R.sup.1 -R.sup.2 -His-R.sup.3, wherein is Val or Thr, R.sup.2 is Gly or D-Ala, R.sup.3 is Leu, ethyl ester or Phe, ethyl ester and R.sup.4 is N-Acetyl, Bromoacetyl, Chloroacetyl, (bis(2-chloroethyl)amino)-L-phenylalanine, or ##STR13## wherein X.sup.1 is Cl or OH and X.sup.2 is Cl or OH (SEQ ID Nos.:3-10).
A bombesin receptor antagonist that is a peptide, wherein the carboxy-terminal residue of said peptide has an ethyl ester, and said peptide has the sequence R.sup.3 -Asn-R.sup.1 -Trp-Ala-Val-R.sup.2 -His-Leu, ethyl ester, wherein R.sup.1 is Gln or His, R.sup.2 is Gly or D-Ala and R.sup.3 is N-Acetyl, Bromoacetyl, Chloroacetyl, (bis(2-chloroethyl)amino)-L-phenylalanine, or ##STR15## wherein X.sup.1 is Cl or OH and X.sup.2 is Cl or OH (SEQ ID Nos.:11-14).
Dependencies are inferred from the claim text.