AEBSF.HCl

AEBSF.HCl is a broad-spectrum, irreversible inhibitor of serine proteases, capable of inhibiting trypsin, kallikrein, plasmin, thrombin, chymotrypsin, and related thrombolytic enzymes. The mechanism of action of AEBSF.HCl involves covalent binding to serine residues, blocking the active center of the protease, thereby inhibiting its activity ^[1].

In vitro, AEBSF.HCl inhibits the production of Aβ in various cell lines. AEBSF.HCl demonstrates a dose-dependent reduction of Aβ in K293 cells transfected with K695 sw, with an IC₅₀ value of about 1 mM, and shows a dose-dependent inhibitory effect in HS 695 and SKN 695 cells transfected with wild-type APP 695, with an IC₅₀ value of about 300 μM. AEBSF.HCl also increases α-cleavage while inhibiting β-cleavage ^[1]. Additionally, as a protease inhibitor, AEBSF.HCl (150 μM) incubated with macrophages for 6 hours can block the lysis of leukemia cells by monocyte-derived macrophages ^[2].

In vivo, AEBSF.HCl (5 mg or 10 mg; i.v.) inhibits rat embryo implantation, with a visible reduction in the number of implanted embryos on day 8 of pregnancy ^[3]. AEBSF.HCl (76.8 mg/kg/d, i.p.) extends the survival time of mice given a lethal infection of Toxoplasma gondii ^[4].

References:

[1] Citron M, Diehl T S, Capell A, et al. Inhibition of amyloid β-protein production in neural cells by the serine protease inhibitor AEBSF. Neuron, 1996, 17(1): 171-179.

[2] Nakabo Y, Pabst M J. Lysis of leukemic cells by human macrophages: inhibition by 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor. Journal of leukocyte biology, 1996, 60(3): 328-336.

[3] Jiang YH, Shi Y, He YP, Du J, Li RS, Shi HJ, Sun ZG, Wang J. Serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibits the rat embryo implantation in vivo and interferes with cell adhesion in vitro. Contraception. 2011 Dec;84(6):642-8.

[4] Buitrago-Rey R, et al. Evaluation of two inhibitors of invasion: LY311727 [3-(3-acetamide-1-benzyl-2-ethyl-indolyl-5-oxy)propane phosphonic acid] and AEBSF [4-(2-aminoethyl)-benzenesulphonyl fluoride] in acute murine toxoplasmosis. J Antimicrob Chemother. 2002 May;49(5):871-4

AEBSF.HCl是丝氨酸蛋白酶广谱的不可逆的抑制剂，可抑制胰凝乳蛋白酶，激肽释放酶，纤溶酶，凝血酶，胰蛋白酶和相关的溶栓酶等。AEBSF.HCl的作用机制是通过与丝氨酸残基共价结合，阻断蛋白酶的活性中心，从而抑制蛋白酶的活性^[1]。

在体外，AEBSF.HCl抑制多种细胞系中的Aβ产生。AEBSF.HCl在转染K695 sw的K293细胞中呈剂量依赖性降低Aβ，IC₅₀值约为1 mM，在转染野生型APP 695的HS 695和SKN 695细胞中呈剂量依赖性抑制作用，IC₅₀值约为300 μM。AEBSF.HCl还能增加α-裂解，抑制β-裂解^[1]。此外，作为蛋白酶抑制剂，AEBSF.HCl（150 μM）与巨噬细胞孵育6小时可以阻止单核细胞衍生的巨噬细胞裂解白血病细胞^[2]。

在体内，AEBSF.HCl(5 mg or 10 mg；i.v.)对大鼠胚胎着床有抑制作用，在妊娠第8天可见着床胚胎数^[3]。AEBSF.HCl（76.8 mg/kg/d，i. p.）延长了被给予致死性刚地弓形虫(Toxoplasma gondii)感染的小鼠生存时间^[4]。