BW2258U89 - A GRP RECEPTOR ANTAGONIST WHICH INHIBITS SMALL-CELL LUNG-CANCER GROWTH

The ability of reduced peptide bond analogues of gastrin releasing pep tide (GRP) to antagonize small cell lung cancer (SCLC) GRP receptors w as investigated. BW462U89, BW1023U90, BW2123U89 and BW2258U89 inhibite d binding of (I-125-Tyr(4)) BN to NCI-H345 cells with IC50 values of 5 , 6, 140 and 10 nM respectively. The GRP analogues had no effect on ba sal cytosolic Ca2+ but inhibited the increase caused by 10 nM BN. BW46 2U89 reversibly blocked the increase in cytosolic Ca2+ caused by BN. T he GRP analogues (1 mu M) inhibited NCI-H345 colony formation in the a bsence or presence of 10 nM BN. Also, BW2258U89 (0.4 mg/kg, s.c. daily ) inhibited xenograft growth in nude mice. These data indicate that BW 2258U89 inhibits SCLC growth in vitro and in vivo.