AMY-101 (Cp40) is the efficient inhibitor of the central complement component C3, with sub-nanomolar affinity for C3 (KD=0.5nmol/L)[1]. AMY-101 is involved in regulating the immune response, regulating the complement system and the release of inflammatory mediators[2]. AMY-101 has been used in immune response research, anti-inflammatory experiments and antiviral study[3].
In vitro, AMY-101 treatment (20μmol/L) for 72 hours significantly reduced the production of pro-inflammatory mediators in human THP-1 cells[4]. Treatment of SV40-immortalized porcine aortic endothelial cells with AMY-101 at 20μg/ml for 1 hour almost completely inhibited the deposition of C3 fragments and C5b-9 on the cells[5].
In vivo, AMY-101 treatment (4mg/kg; 28 days) via subcutaneous injection daily to adult cynomolgus monkeys can significantly reduce the clinical indices measured for periodontal inflammation and tissue destruction[1]. In sensitized male rhesus monkeys, intramuscular injection of AMY-101 (2mg/kg/day; I.M.) for 16 days can inhibit lymphocyte activation and proliferation, prevent antibody-mediated rejection reactions, and prolong the survival period of kidney transplantation[6].
References:
[1] Kajikawa T, Briones R A, Resuello R R G, et al. Safety and efficacy of the complement inhibitor AMY-101 in a natural model of periodontitis in non-human primates[J]. Molecular Therapy Methods & Clinical Development, 2017, 6: 207-215.
[2] Li J, Xu Z, Ayre W N, et al. AMY-101 as complement C3 inhibitor for periodontitis therapy: mechanisms, efficacy, and clinical translation[J]. Frontiers in Immunology, 2025, 16: 1587126.
[3] Mastaglio S, Ruggeri A, Risitano A M, et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101[J]. Clinical immunology, 2020, 215: 108450.
[4] Fernandes D C, Silva-de-França F, Pohl P C, et al. Cp40-mediated complement C3 inhibition dampens inflammasome activation and inflammatory mediators storm induced by Bitis arietans venom[J]. International Immunopharmacology, 2025, 147: 113701.
[5] Wang J, Wang L, Xiang Y, et al. Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40[J]. Clinical Immunology, 2016, 162: 37-44.
[6] Schmitz R, Fitch Z W, Schroder P M, et al. C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates[J]. Nature Communications, 2021, 12(1): 5456.
AMY-101（Cp40）是一种高效的中枢补体成分C3抑制剂，对C3具有亚纳摩尔级亲和力（KD=0.5nmol/L）[1]。AMY-101通过调控补体系统和炎症介质释放参与免疫反应调节[2]。AMY-101已应用于免疫应答研究、抗炎实验及抗病毒研究[3]。
在体外，20μmol/L浓度的AMY-101处理人THP-1细胞72小时后，能显著降低促炎介质的产生[4]。使用20μg/ml剂量的AMY-101处理SV40永生化猪主动脉内皮细胞1小时，几乎完全抑制了细胞表面C3片段和C5b-9的沉积[5]。
在体外，成年食蟹猴每日皮下注射4mg/kg剂量的AMY-101持续28天，可显著改善牙周炎症和组织破坏的临床指标[1]。对致敏雄性恒河猴进行16天肌肉注射治疗（2mg/kg/day），能抑制淋巴细胞活化增殖，预防抗体介导的排斥反应，并延长肾移植后的存活期[6]。