4-IBP

Description: 4-IBP is a novel and selective sigma1 (sigma1) agonist with high affinity for the sigma1 receptor with Ki of 1.7 nM and a moderate affinity for the sigma2 receptor (Ki = 25.2 nM). Although the molecular function of sigma receptors has not been fully defined and the natural ligand(s) is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-IBP has revealed weak antiproliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

References: Neoplasia. 2007 May; 9(5):358-69.