The bombesin (Bn) receptor family includes the gastrin-releasing peptide (GRPR) and neuromedin B (NMBR) receptors, Bn receptor subtype 3 (BRS-3) and Bn receptor subtype 4 (BB4). In particular, GRP affects several systems in mammals, including neuroendocrine regulation, gastrointestinal secretion, and cell proliferation. Furthermore, it is involved in the development and regulation of the immune response, acting directly on the immune cells that express the GRP receptor (GRPR). Moreover, the binding of BN or GRP to their receptors raised the possibility that their antagonists might be useful as endocrine therapy for tumors. GRP receptor antagonists also suppress the growth of many experimental tumors including prostatic, breast, ovarian, lung, and pancreatic cancers.
RC-3095 is a selective bombesin/gastrin releasing peptide receptor (GRPR) antagonist. RC-3095 has anti-inflammatory properties in a variety of inflammation models by reducing the release of pro-inflammatory cytokines (such as TNF-α and IL-1β) and the activation and migration of mononuclear cells to sites of inflammation. For example, in collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA) mice, administration of RC-3095 reduces the levels of proinflammatory cytokines, and diminishes GRPR expression.
Besides, RC-3095 also has potent antitumor effects. For instance, RC-3095 exhibits a powerful inhibition effect on pancreatic cancer CFPAC-1 cell proliferation. In addition, in nude mice bearing xenografts of CFPAC-1 cell, RC-3095 significantly reduces the volume and weight of tumors. Furthermore, this compound treatment decreases GRPR/BRS-3 positive cells and protein expression in tumors.
In general, RC-3095 is a selective GRPR antagonist with effective anti-inflammatory and anti-cancer activities.