RC-3095 is a gastrin-releasing peptide (GRP) receptor antagonist[1]. GRP affects several systems in mammals, including neuroendocrine regulation, gastrointestinal secretion, and cell proliferation[2]. RC-3095 works by blocking bombesin/GRP receptors and is considered an anticancer drug with clinical application value[3].
In vitro, treatment with RC-3095 for 48h inhibited proliferation at 0.1nM but stimulated proliferation at 100nM in Neuro2a murine neuroblastoma cells[4].
In vivo, RC-3095 treatment (1mg/kg; s.c.; twice daily for 2 or 10 days) significantly reduced neutrophil migration, mechanical hypernociception, and proteoglycan loss in mice with AIA (antigen-induced arthritis)[2]. Administration of RC-3095 (0.3 or 1mg/kg; s.c.; twice daily for 10 days) significantly decreased arthritis clinical scores and reduced disease severity as assessed by histological analysis in mice with CIA (collagen-induced arthritis)[2]. A single intraperitoneal injection of RC-3095 (0.2 or 1.0mg/kg) 30 minutes before behavioral testing impaired short-term and long-term inhibitory avoidance memory in mice, but did not affect their cognitive memory[3].
References:
[1]Qin Y, Halmos G, Cai RZ, Szoke B, Ertl T, Schally AV. Bombesin antagonists inhibit in vitro and in vivo growth of human gastric cancer and binding of bombesin to its receptors. J Cancer Res Clin Oncol. 1994;120(9):519-528.
[2] Oliveira PG, Grespan R, Pinto LG, et al. Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide receptor, in experimental arthritis. Arthritis Rheum. 2011;63(10):2956-2965.
[3] Roesler R, Kopschina MI, Rosa RM, Henriques JA, Souza DO, Schwartsmann G. RC-3095, a bombesin/gastrin-releasing peptide receptor antagonist, impairs aversive but not recognition memory in rats. Eur J Pharmacol. 2004;486(1):35-41.
[4] Abujamra AL, Almeida VR, Brunetto AL, Schwartsmann G, Roesler R. A gastrin-releasing peptide receptor antagonist stimulates Neuro2a neuroblastoma cell growth: prevention by a histone deacetylase inhibitor. Cell Biol Int. 2009;33(8):899-903.
RC-3095是一种胃泌素释放肽（GRP）受体拮抗剂[1]。GRP影响哺乳动物的多个系统，包括神经内分泌调节、胃肠道分泌和细胞增殖[2]。RC-3095通过阻断胃泌素释放肽/GRP受体发挥作用，被认为是一种具有临床应用价值的抗癌药物[3]。
体外实验中，在Neuro2a小鼠神经母细胞瘤细胞中，0.1nM的RC-3095处理48小时可抑制细胞增殖，而100nM的RC-3095则可促进细胞增殖[4]。
体内实验中，皮下注射RC-3095（1mg/kg；每日两次；持续2天或10天）可显著减少抗原诱导关节炎（AIA）小鼠模型中中性粒细胞迁移、机械性痛觉过敏和蛋白聚糖丢失[2]。皮下注射RC-3095（0.3或1mg/kg；每日两次；持续10天）可显著降低胶原诱导关节炎（CIA）小鼠的关节炎临床评分[2]。在行为测试前30分钟，单次腹腔注射RC-3095（0.2或1.0mg/kg）会损害小鼠的短期和长期抑制性回避记忆，但不会影响其识别记忆[3]。