Mirococept

Mirococept (APT070) is an antibody targeting to complement system C3b/C4b, as well as a membrane-localizing C3 convertase inhibitor. Mirococept reduces the release of C-peptide and pro-inflammatory cytokines, and reduces the infiltration of inflammatory cells. Mirococept reduces intraislet inflammation, which is beneficial to islet transplantation. Mirococept also inhibits increased intestinal and pulmonary vascular permeability to reduce neutrophil influx[1][2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Immunology/Inflammation >> Complement System

Research Areas >> Inflammation/Immunology

C3b, C4b, C3 convertase[1]

Mirococept (0.4-1.6 μM；1 小时) 结合胰岛，浓度为 0.4 μM 时，不抑制胰岛素对葡萄糖的分泌反应，也不抑制受体介导的激动剂卡巴胆碱[1]。 Mirococept (0.4 μM；1 小时) 在体外防止激活补体的产生，并减少胰岛中 C4d (补体激活指示剂) 和 C5b-9 (导致细胞裂解) 的沉积[1]。

Mirococep 处理的胰岛移植到糖尿病人源化 NSG 小鼠体内，减少人类胰岛破坏，并抑制早期促炎细胞因子的产生[1]。 Mirococept (1-10 mg/kg；静脉注射；单剂量) 剂量依赖性地改善大鼠轻度再灌注损伤模型。 Mirococept 显着抑制小鼠缺血再灌注损伤 (I/RI) 模型中血管通透性和中性粒细胞募集的增加[2]。 Animal Model: Male Wistar rats with ischaemia and reperfusion injury (I/RI)[2] Dosage: 1 mg/kg, 3 mg/kg, and 10 mg/kg Administration: Intravenous injection; 15 min prior to the reperfusion of the superior mesenteric artery (SMA) Result: Resulted significant reduction of vascular leakage at doses as low as 1 mg/kg (lungs) or 3 mg/kg (intestine). Greatly reduced vascular leakage and MPO levels at 10 mg/kg.

[1]. Xiao F, et al. APT070 (mirococept), a membrane-localizing C3 convertase inhibitor, attenuates early human islet allograft damage in vitro and in vivo in a humanized mouse model. Br J Pharmacol. 2016 Feb;173(3):575-87.  

[2]. Souza DG, et al. APT070 (Mirococept), a membrane-localised complement inhibitor, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury. Br J Pharmacol. 2005 Aug;145(8):1027-34.