Receptor-specific somatostatin analogs: Correlations with biological activity

A number of cyclic and linear somatostatin (SRIF) analogs have now been found to have promising levels of selectivity for rodent somatostatin receptors (rsst(2,3,5)), but not sst(1) and sst(4), Comparisons between binding affinities for these and transfected human receptors are just beginning to emerge and we present results from a comparison of affinities of several key families of peptides for sst(2) present on rat AR42J cells and on cells transfected with human (h)sst(2). The typical cyclic octapeptide analogs, octreotide, lanreotide, and RC-160, exhibited similar affinities to SRIF for rsst(2), but somewhat lower affinities for the human receptor. Affinities of several analogs for transfected hsst(5) were also measured. As with the rat receptor, octreotide-related analogs had low affinity for hsst(5). The highly specific rsst(5) analog, DC-23-99, was less so for the human receptor; however, a D-Tyr(1) version of DC-23-99 had subnanomolar affinity (K-i, 0.68 nmol/L) and high selectivity, A new extended-ring analog, BIM-23268D, showed superior affinity to DC-23-99 and even to SRIF and SRIF-28 for hsst(5) (K-i, 0.38 nmol/L), and had the highest sst(5)/sst(2) selectivity ratio of any analog that we have tested thus far. Copyright (C) 1996 by W.B. Saunders Company