Bepridil hydrochloride hydrate is a long-acting calcium channel blocker. Bepridil hydrochloride hydrate blocks Ca²⁺, Na⁺, and K⁺ channels and inhibits calmodulin. Bepridil hydrochloride hydrate can be used in research related to chronic stable angina and arrhythmias[1-4].
In vitro, Bepridil hydrochloride hydrate (25-50μM) was used to treat A2058, A375, and C8161 melanoma cells preloaded with Fluo-4 AM (5μM) for 40 minutes. Bepridil hydrochloride hydrate significantly increased cytoplasmic Ca²⁺ signal levels; Bepridil hydrochloride hydrate (10-50μM) was used to treat A2058 melanoma cells for 18-24 hours, causing G0/G1 phase cell cycle arrest and enhanced apoptosis[5]. Bepridil hydrochloride hydrate (0.78–200μM) was used to treat Vero E6 or A549/ACE2 cells infected with SARS-CoV-2 (MOI=0.5) for 3 days and A549/ACE2 cells for 4 days. Bepridil hydrochloride hydrate prevented virus-induced cytopathic effects and inhibited viral replication[6].
In vivo, Bepridil hydrochloride hydrate (5mg/kg/day) was intraperitoneally injected into NSG mice intravenously transplanted with CLL cells for 20 days. Bepridil hydrochloride hydrate significantly reduced the percentage of leukemic cell infiltration in the spleen by enhancing apoptosis and decreasing NOTCH1 activation[7]. Bepridil hydrochloride hydrate (12mg/kg) was intraperitoneally injected once or twice daily into BALB/c mice infected with Marburg virus (195PFU) for 10 days. Bepridil hydrochloride hydrate significantly increased the survival rate of infected mice[8].
References:
[1] Pang DC, Sperelakis N. Inhibitory action of bepridil (CERM-1978) on calcium binding to cardiac sarcolemma of guinea pig. Biochem Pharmacol. 1981 Aug 15;30(16):2356-8.
[2] Mras S, Sperelakis N. Bepridil (CERM-1978) an verapamil depression of contractions of rabbit aortic rings. Blood Vessels. 1981;18(4-5):196-205.
[3] Mras S, Sperelakis N. Bepridil (CERM-1978) blockade of action potentials in cultured rat aortic smooth muscle cells. Eur J Pharmacol. 1981 Apr 24;71(1):13-9.
[4] Flaim SF, Stranieri MT, Mathiasen JR. Effects of Bepridil hydrochloride hydrate on cardiocirculatory dynamics, coronary vascular resistance, and cardiac output distribution in normal, conscious rats. J Cardiovasc Pharmacol. 1988 Mar;11(3):363-72.
[5] Liu Z, Cheng Q, Ma X, et al. Suppressing Effect of Na+/Ca2+ Exchanger (NCX) Inhibitors on the Growth of Melanoma Cells. Int J Mol Sci. 2022 Jan 14;23(2):901.
[6] Vatansever EC, Yang KS, Drelich AK, et al. Bepridil is potent against SARS-CoV-2 in vitro. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2012201118.
[7] Baldoni S, Del Papa B, Dorillo E, et al. Bepridil exhibits anti-leukemic activity associated with NOTCH1 pathway inhibition in chronic lymphocytic leukemia. Int J Cancer. 2018 Aug 15;143(4):958-970.
[8] DeWald LE, Dyall J, Sword JM, et al. The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease. J Infect Dis. 2018 Nov 22;218(suppl_5):S588-S591.
Bepridil hydrochloride hydrate是一种长效的钙通道阻滞剂。Bepridil hydrochloride hydrate可阻滞Ca²⁺、Na⁺及K⁺通道并抑制钙调蛋白。Bepridil hydrochloride hydrate可用于慢性稳定型心绞痛和心律失常的相关研究[1-4]。
在体外，Bepridil hydrochloride hydrate（25-50μM）处理预加载Fluo-4 AM（5μM）的A2058、A375和C8161黑色素瘤细胞40分钟。Bepridil hydrochloride hydrate显著增加胞质Ca²⁺信号水平；Bepridil hydrochloride hydrate（10-50μM）处理A2058黑色素瘤细胞18-24小时，引起G0/G1期细胞周期阻滞和增强凋亡[5]。Bepridil hydrochloride hydrate（0.78–200μM）处理SARS-CoV-2（MOI=0.5）感染的Vero E6或A549/ACE2细胞3天及A549/ACE2细胞4天。Bepridil hydrochloride hydrate可预防病毒诱导的细胞病变效应，同时抑制病毒复制[6]。
在体内，Bepridil hydrochloride hydrate（5mg/kg/day）腹腔注射于静脉移植CLL细胞的NSG小鼠，持续20天。Bepridil hydrochloride hydrate显著减少了脾脏中白血病细胞浸润的百分比，通过增强凋亡和降低NOTCH1激活[7]。Bepridil hydrochloride hydrate（12mg/kg）每天一次或两次腹腔注射于感染马尔堡病毒（195PFU）的BALB/c小鼠，持续10天。Bepridil hydrochloride hydrate显著提高了感染小鼠的存活率[8]。