Benzamidine (hydrochloride) is a reversible, competitive trypsin-like serine protease inhibitor. Benzamidine inhibits the activities of tryptase (Ki=20μM), trypsin (Ki=21μM), uPA (Ki=97μM, factor Xa (Ki=110μM), thrombin (Ki=320μM), and tPA (Ki=750μM). Benzamidine can be used in studies related to the coagulation and fibrinolytic systems, physiological enzymology, and relevant pharmacology[1-4].
In vitro, human fetal lung fibroblasts were pretreated with Benzamidine (1–100μM) for 60 minutes, followed by stimulation with human mast cell tryptase (17.6mU/ml) for 48 hours. Benzamidine inhibited tryptase-induced fibroblast proliferation[5]. HEK293 cells incubated with KIF (10μM) and SWA (50μM) were treated with Benzamidine (5mM) for 48 hours. Benzamidine promoted cellular corin expression and inhibited corin autocleavage[6].
In vivo, Benzamidine (100μM; 200μl) was administered by intragastric gavage to MC903-induced atopic dermatitis (AD) model mice for 14 consecutive days. Benzamidine significantly alleviated the inflammatory phenotype and inflammatory infiltration in the mice[7].
References:
[1] Katz BA, Mackman R, Luong C, et al. Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator. Chem Biol. 2000 Apr;7(4):299-312.
[2] Cairns JA, Walls AF. Mast cell tryptase stimulates the synthesis of type I collagen in human lung fibroblasts. J Clin Invest. 1997 Mar 15;99(6):1313-21.
[3] Ristow SS, Starkey JR, Hass GM. In vitro effects of protease inhibitors on murine natural killer cell activity. Immunology. 1983 Jan;48(1):1-8.
[4] Wang X, Jin X, Xie Z, et al. Benzamidine Conjugation Converts Expelled Potential Active Agents into Antifungals against Drug-Resistant Fungi. J Med Chem. 2023 Oct 12;66(19):13684-13704.
[5] Akers IA, Parsons M, Hill MR, et al. Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2. Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L193-201.
[6] Wang H, Liu YS, Peng Y, et al. Golgi α-mannosidases regulate cell surface N-glycan type and ectodomain shedding of the transmembrane protease corin. J Biol Chem. 2023 Oct;299(10):105211.
[7] Jia T, Che D, Zheng Y, et al. Mast Cells Initiate Type 2 Inflammation through Tryptase Released by MRGPRX2/MRGPRB2 Activation in Atopic Dermatitis. J Invest Dermatol. 2024 Jan;144(1):53-62.e2.
Benzamidine (hydrochloride)是一种可逆的、竞争性胰蛋白酶样丝氨酸蛋白酶抑制剂。Benzamidine可抑制Tryptase（Ki=20μM）、Trypsin（Ki=21μM）、uPA（Ki=97μM）、Factor Xa（Ki=110μM）、Thrombin（Ki=320μM）和tPA（Ki=750μM）的活性。Benzamidine可用于凝血与纤溶系统、生理酶学及相关药理学研究[1-4]。
在体外，Benzamidine（1-100μM）预处理人胎儿肺成纤维细胞60分钟，随后以人肥大细胞类胰蛋白酶（17.6mU/ml）刺激48小时。Benzamidine抑制类胰蛋白酶诱导的成纤维细胞增殖[5]。Benzamidine（5mM）处理KIF（10μM）和SWA（50μM）孵育的HEK293细胞48小时。Benzamidine促进了细胞的corin表达，并抑制corin自切割[6]。
在体内，Benzamidine（100μM；200μl）灌胃给药于MC903诱导的AD模型小鼠，连续14天。Benzamidine显著减轻了小鼠的炎症表型和炎症浸润[7]。