β-Aminopropionitrile

β-Aminopropionitrile (BAPN) is a specific irreversible lysine oxidase (LOX) inhibitor with an IC₅₀ value of approximately 3-8μM ^[1]. β-Aminopropionitrile targets the active site of LOX or LOXL isoenzymes ^[2]. β-Aminopropionitrile can cross-link elastin fibers and collagen fibers to maintain the homeostasis of the elastic layer ^[3].

In vitro, β-Aminopropionitrile (500μM) treated cervical cancer HeLa and SiHa cells for 48 hours, inactivating LOX activity and significantly inhibiting hypoxia-induced cell invasion. The invasion ability of the two cell lines was inhibited by 50% and 60% respectively^[4]. β-Aminopropionitrile (1.0mg/mL, approximately 14.3μM) treated LX-2 cells for 24 hours and significantly down-regulated the expression of LOXL2 and α-SMA induced by TGF β ^[5].

In vivo, β-Aminopropionitrile (100 mg/kg) added to the drinking water of rats fed a high-fat diet for 6 weeks reduced fasting blood glucose and insulin levels, reduced homeostasis model assessment (HOMA) index, and improved obesity and adipose tissue fibrosis. phenomenon ^[6]. Adding β-Aminopropionitrile (1000 mg/kg) to drinking water and feeding C57BL/6 male mice for 4 weeks significantly reduced the weight of the mice and reduced plasma triglyceride and cholesterol levels ^[7].

References:

[1] Bhave G, Cummings C F, Vanacore R M, et al. Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis[J]. Nature chemical biology, 2012, 8(9): 784-790.

[2] Rodriguez H M, Vaysberg M, Mikels A, et al. Modulation of lysyl oxidase-like 2 enzymatic activity by an allosteric antibody inhibitor[J]. Journal of biological chemistry, 2010, 285(27): 20964-20974.

[3] Kawai T, Takayanagi T, Forrester S J, et al. Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile–Induced Abdominal Aortic Aneurysm[J]. Hypertension, 2017, 70(5): 959-963.

[4] Yang X, Li S, Li W, et al. Inactivation of lysyl oxidase by β-aminopropionitrile inhibits hypoxia-induced invasion and migration of cervical cancer cells[J]. Oncology reports, 2013, 29(2): 541-548.

[5] Cheng F, Yang F, Wang Y, et al. Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP/LOXL2 pathway[J]. Journal of Nanobiotechnology, 2023, 21(1): 195.

[6] Miana M, Galán M, Martínez-Martínez E, et al. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats[J]. Disease models & mechanisms, 2015, 8(6): 543-551.

[7] Ren W, Liu Y, Wang X, et al. β-Aminopropionitrile monofumarate induces thoracic aortic dissection in C57BL/6 mice[J]. Scientific reports, 2016, 6(1): 28149.

β-Aminopropionitrile（BAPN）是一种特异的不可逆赖氨酸氧化酶（LOX）抑制剂，IC₅₀值约为3-8μM^[1]。β-Aminopropionitrile 靶向LOX或LOXL同工酶的活性位点^[2]。β-Aminopropionitrile可使弹性蛋白纤维和胶原纤维交联，维持弹性层的稳态^[3]。

在体外，β-Aminopropionitrile（500μM）处理宫颈癌HeLa和SiHa细胞48h，灭活了LOX活性，显著抑制了缺氧诱导的细胞侵袭，两种细胞系的侵袭能力分别被抑制了50%和60%^[4]。β-Aminopropionitrile（1.0 mg/mL，约14.3μM）处理 LX-2细胞24h，显著下调了TGF β诱导的LOXL2和 α-SMA表达^[5]。

在体内，β-Aminopropionitrile（100mg/kg）加入到高脂饮食大鼠的饮用水中喂养6周，降低了大鼠空腹血糖和胰岛素水平，降低了稳态模型评估（HOMA）指数，并改善了肥胖和脂肪组织纤维化现象^[6]。β-Aminopropionitrile（1000mg/kg）加入到饮用水中喂养C57BL/6 雄性小鼠4周，显著减轻了小鼠体重，降低了血浆甘油三酯和胆固醇水平^[7]。