STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF NOVEL SOMATOSTATIN ANALOGSWITH ANTITUMOR-ACTIVITY

A series of new somatostatin analogs were synthesized in order to stud y the relative importance of specific substitutions in relation to sel ectivity between their endocrine and antitumor effects. Substitutions were carried out in all positions, except for Lys in position 5. Pepti des were tested for their ability to inhibit in vitro and in vivo GH r elease, proliferation of the MCF 7 breast carcinoma cell line and tyro sine kinase activity in the HT 29 human colon carcinoma cell line. Sel ective biological activity was achieved in GH release and antitumor ac tivity by the different amino acid substitutions. One of the analogs, with a five-residue ring (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2, TT-232) , was unique. It had no GH release inhibitory activity, but did have s trong tyrosine kinase inhibitory and antiproliferative effects.