Patent Evaluation: Novel LHRH Antagonists

Summary

Novelty: Novel analogues of LHRH are disclosed and are said to be antagonists of LHRH, potentially useful for the treatment of cancerous tumours.

Biology: Receptor binding affinities for human breast cancer cell membranes was demonstrated using labelled LHRH as desribed by Kadar et al. (Proc. Natl. Acad. Sci. USA (1988)

B5:890-894) Affinity constants range from 4.08-48.28 nM. In tests on the growth of Dunning R3327 prostate cancer in rats, compounds of the claim reduced the volume of the tumours by up to half after 7 weeks at 25 μg/day.

Chemistry: Seven synthetic schemes for production of the peptides are presented and twentysix compounds are exemplified; none is specifically claimed. A typical peptide is Ac-DNal(2)D-Phe(4Cl)-D-Pa1(3)Ser-Arg-D-Lys[A₂pr(Car)2]-Leu-Arg-Pro-D-Ala-NH₂, where Ac=acetyl, Na1(2)=3-(2-naphthyl)alanine, Phe(4Cl)4-chlorophenylalanine, Pal(3)=3-(3-pyridyl)-alanine and A₂pr=2,3-diaminopropinic acid.