BIM 23127

BIM 23127 is a highly selective agonist for somatostatin receptor subtype 2 (SSTR2) with a Ki value of 20.9nM^[1]. By binding to SSTR2, BIM 23127 inhibits cAMP accumulation and modulates downstream effectors, thereby exerting its biological activities^[2]. BIM 23127 is used to investigate the role of somatostatin in regulating hormone secretion, and cell proliferation^[3]. BIM 23127 has also demonstrated potential in suppressing tumor and cancer cell proliferation^[4].

In vitro, pretreatment of RAW-Blue macrophages, PANC-1 cells, and SW-620 cells with BIM 23127 (12.5μg/mL) for 1 hour, followed by stimulation with the CB1 receptor agonist AM-404 (2.57μg/mL), significantly inhibited Neu-1 sialidase activity and blocked CB1 receptor-mediated activation of the NF-κB signaling pathway^[5]. In HTC-WT cells (rat hepatoma cells), pretreatment with BIM 23127 (333μg/mL) for 30 minutes, followed by stimulation with insulin (100nM) or bombesin, markedly suppressed insulin-induced Neu1 sialidase activity and inhibited neuromedin B receptor (NMBR)-mediated insulin receptor signaling pathway activation^[6].

In vivo, intracerebroventricular pretreatment with BIM 23127 (3nmol/animal) 30 minutes prior to bombesin (0.03nmol/animal) administration significantly attenuated bombesin-induced shortening of the urinary interval in rats and blocked bombesin receptor subtype-1 (BB1)-mediated hyperreflexia of the mitcurition reflex^[7]. Intraperitoneal pretreatment with BIM 23127 (16–64nmol/kg) 15 minutes prior to behavioral testing significantly impaired memory acquisition in a mouse inhibitory avoidance learning task, with the most pronounced effect observed at a dose of 32nmol/kg^[8].

References:
[1] Ladenheim EE, Taylor JE, Coy DH, et al. Blockade of feeding inhibition by neuromedin B using a selective receptor antagonist. Eur J Pharmacol. 1994 Dec 12;271(1):R7-9.
[2] Herold CL, Behm DJ, Buckley PT, et al. The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensin-II receptors. Br J Pharmacol. 2003 May;139(2):203-7.
[3] Ladenheim EE, Taylor JE, Coy DH, et al. Caudal hindbrain neuromedin B-preferring receptors participate in the control of food intake. Am J Physiol. 1997 Jan;272(1 Pt 2):R433-7.
[4] Jaeger M, Ghisleni EC, Fratini L, et al. Viability of D283 medulloblastoma cells treated with a histone deacetylase inhibitor combined with bombesin receptor antagonists. Childs Nerv Syst. 2016 Jan;32(1):61-4.
[5] Bunsick DA, Matsukubo J, Aldbai R, et al. Functional Selectivity of Cannabinoid Type 1 G Protein-Coupled Receptor Agonists in Transactivating Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition Metastatic Phenotype. Cells. 2024 Mar 8;13(6):480.
[6] Alghamdi F, Guo M, Abdulkhalek S, et al. A novel insulin receptor-signaling platform and its link to insulin resistance and type 2 diabetes. Cell Signal. 2014 Jun;26(6):1355-68.
[7] Shimizu T, Shimizu S, Higashi Y, et al. A Stress-Related Peptide Bombesin Centrally Induces Frequent Urination through Brain Bombesin Receptor Types 1 and 2 in the Rat. J Pharmacol Exp Ther. 2016 Mar;356(3):693-701.
[8] Santo-Yamada Y, Yamada K, Wada E, et al. Blockade of bombesin-like peptide receptors impairs inhibitory avoidance learning in mice. Neurosci Lett. 2003 Apr 3;340(1):65-8.

BIM 23127是一种生长抑素受体（SSTR）亚型2（SSTR2）的高选择性激动剂（Ki=20.9nM）^[1]。BIM 23127通过与SSTR2结合，抑制cAMP的积累和调节下游效应器，从而发挥其生物学作用^[2]。BIM 23127可用于研究生长抑素在调节激素分泌、细胞增殖的作用^[3]。BIM 23127还显示出抑制肿瘤和癌细胞生长的潜力^[4]。

在体外，BIM 23127（12.5μg/mL）预处理RAW-Blue巨噬细胞、PANC-1细胞及SW-620细胞1小时，随后以CB1受体激动剂（AM-404；2.57μg/mL）刺激，BIM 23127显著抑制Neu-1唾液酸酶活性，同时阻断CB1受体介导的NF-κB信号通路激活^[5]。BIM 23127（333μg/mL）预处理HTC-WT细胞（大鼠肝癌细胞）30分钟，随后以胰岛素（100nM）或蛙皮素（bombesin）刺激，显著抑制胰岛素诱导的Neu1唾液酸酶活性，同时阻断神经介素B受体（NMBR）介导的胰岛素受体信号通路激活^[6]。

在体内，BIM 23127（3nmol/只）侧脑室预处理30分钟，显著抑制了蛙皮素（0.03nmol/只）诱导的大鼠排尿间隔缩短，同时阻断了脑内蛙皮素受体1型（BB1）介导的排尿反射亢进^[7]。BIM 23127（16-64nmol/kg）腹腔注射预处理15分钟，BIM 23127显著损害了小鼠抑制性回避学习任务的记忆获得能力，且该效应在32nmol/kg剂量时最为明显^[8]。