Narsoplimab (anti-MASP-2) is a human immunoglobulin gamma 4 (IgG4) monoclonal antibody against mannose-binding protein-associated serine protease 2 (MASP-2) achieved by high affinity (zymogen form: KD=0.062nM, IC50~3.4nM; enzymatically active form: KD=0.089nM) to block lectin pathway[1]. Narsoplimab selectively inhibits human C5b-9, IC50~1nM; its potency in cynomolgus monkey serum was IC50~33nM. The efficiency of Narsoplimab is EC50=6.1μg/mL ex vivo and IC50=33nM in vitro [1]. Narsoplimab shows positive potential results in hematopoietic stem-cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) in a clinical trial[2].
In vitro experiments show that Narsoplimab act as a positive control to evaluate inhibitory efficiency among the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2(purified human MASP-2; 2.4μg/ml at 37°C; 3h)[3]. Moreover, MASP2 inhibition by Narsoplimab suppresses endotheliopathies characteristic of transplant-associated thrombotic microangiopathy (primary human neonatal microvascular endothelial cell; 10µg/ml; 5h)[4].
References:
[1] Dudler, Thomas et al. “Development and characterization of narsoplimab, a selective MASP-2 inhibitor, for the treatment of lectin-pathway-mediated disorders.” *Frontiers in immunology* vol. 14 1297352. 8 Nov. 2023, doi:10.3389/fimmu.2023.1297352
[2] Khaled, Samer K et al. “Narsoplimab, a Mannan-Binding Lectin-Associated Serine Protease-2 Inhibitor, for the Treatment of Adult Hematopoietic Stem-Cell Transplantation-Associated Thrombotic Microangiopathy.” *Journal of clinical oncology : official journal of the American Society of Clinical Oncology* vol. 40,22 (2022): 2447-2457. doi:10.1200/JCO.21.02389
[3] Gao, Ting et al. “Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation.” *Signal transduction and targeted therapy*vol. 7,1 318. 14 Sep. 2022, doi:10.1038/s41392-022-01133-5
[4]Elhadad, Sonia et al. “MASP2 inhibition by narsoplimab suppresses endotheliopathies characteristic of transplant-associated thrombotic microangiopathy: in vitro and ex vivo evidence.” Clinical and experimental immunology vol. 213,2 (2023): 252-264. doi:10.1093/cei/uxad055
Narsoplimab （anti-MASP-2）是一种抗甘露糖结合蛋白相关丝氨酸蛋白酶2 （MASP-2）的人免疫球蛋白γ 4 （IgG4）单克隆抗体，以高亲和力阻断凝集素通路(酶原形式：KD=0.062nM, IC50~3.4nM；酶活性形式：KD=0.089nM)[1]。Narsoplimab能够选择性抑制人C5b-9，IC50值为1nM。Narsoplimab在食蟹猴血清中对C5b-9的IC50值为33nM。Narsoplimab在体内的EC50 为6.1μg/mL，在体外IC50=33nM[1]。在一项临床试验中，Narsoplimab在造血干细胞移植相关血栓性微血管病（HSCT-TMA）中显示出积极的潜在结果。
体外实验中，Narsoplimab能够作为阳性对照，评价SARS-CoV、MERS-CoV和SARS-CoV-2（纯化人MASP-2; 2.4μg/ml; 37℃; 3h）对N蛋白的抑制效果[3]。此外，Narsoplimab抑制MASP-2 导致的相关血栓性微血管病变（原发性人新生儿微血管内皮细胞; 10µg/ml; 5h）[4]。