(2-Chloropyridin-4-yl)methanamine hydrochloride is a highly selective inhibitor of lysyl oxidase-like protein-2 (LOXL2), with an IC50 of 126nM[1]. LOXL2 is a secreted copper-dependent amine oxidase that catalyzes the cross-linking of lysine residues in collagen and elastin, thereby regulating extracellular-matrix remodeling and playing a key role in tumor metastasis, fibrosis, and tissue repair[2]. (2-Chloropyridin-4-yl)methanamine hydrochloride is widely used in the research of tumor invasion, metastasis and epithelial-mesenchymal transition (EMT) mechanisms[3][4].
In vitro, treatment of cervical cancer cells (SIHA and HELA) with (2-Chloropyridin-4-yl)methanamine hydrochloride (0–2792.5μM; 24–96h) significantly inhibits cell viability (with IC50 values of 465.25μM for SIHA cells and 246.909μM for HELA cells), cell migration, invasion, and proliferation, induces apoptosis, and suppresses malignant transformation by reversing the LOXL2-induced epithelial-mesenchymal transition (EMT) process in a concentration-dependent manner[5]. Treatment of Huh7 and Hep3B cells with (2-Chloropyridin-4-yl)methanamine hydrochloride (50nM; 12h) significantly upregulates FBP1 expression, downregulates Snail, HIF-1α, and VEGF expression, and inhibits cell proliferation, glycolysis, and angiogenesis[6].
In vivo, (2-Chloropyridin-4-yl)methanamine hydrochloride(100μg/kg/day; i.p.; 4 weeks) significantly reduced atrial fibrosis and vulnerability to atrial fibrillation, attenuated atrial inflammation and cardiac hypertrophy, and reversed the activation of the TGF-β1/Smad2/3 pathway and collagen I expression in Angiotensin II-induced mice atrial fibrillation (AF) models[7].
References:
[1] Hutchinson JH, Rowbottom MW, Lonergan D, et al. Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX. ACS Med Chem Lett. 2017;8(4):423-427.
[2] Moon HJ, Finney J, Ronnebaum T, Mure M. Human lysyl oxidase-like 2. Bioorg Chem. 2014;57:231-241.
[3] Ye C, Jiang S, Zeng T, He S, Cao J, Xiao J. The role of LOXL2 in tumor progression, immune response and cellular senescence: a comprehensive analysis. Discov Oncol. 2024;15(1):245.
[4] Ferreira S, Saraiva N, Rijo P, Fernandes AS. LOXL2 Inhibitors and Breast Cancer Progression. Antioxidants (Basel). 2021;10(2):312.
[5] Peng T, Lin S, Meng Y, et al. LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT). Cell Cycle. 2022;21(17):1827-1841.
[6] Fan Z, Zheng W, Li H, et al. LOXL2 upregulates hypoxia inducible factor 1α signaling through Snail FBP1 axis in hepatocellular carcinoma cells. Oncol Rep. 2020;43(5):1641-1649.
[7] Wu Y, Can J, Hao S, Qiang X, Ning Z. LOXL2 Inhibitor Attenuates Angiotensin II-Induced Atrial Fibrosis and Vulnerability to Atrial Fibrillation through Inhibition of Transforming Growth Factor Beta-1 Smad2/3 Pathway. Cerebrovasc Dis. 2022;51(2):188-198.
(2-Chloropyridin-4-yl)methanamine hydrochloride是一种高选择性的赖氨酰氧化酶样蛋白-2（LOXL2）抑制剂，其IC50为126nM[1]。LOXL2是一种分泌型铜依赖性胺氧化酶，可催化胶原蛋白和弹性蛋白中赖氨酸残基的交联，从而调节细胞外基质重塑，并在肿瘤转移、纤维化和组织修复中发挥关键作用[2]。(2-Chloropyridin-4-yl)methanamine hydrochloride广泛用于肿瘤侵袭、转移及上皮-间质转化（EMT）机制的研究[3][4]。
在体外，(2-Chloropyridin-4-yl)methanamine hydrochloride（0–2792.5μM；24–96h）处理宫颈癌细胞（SIHA和HELA）显著抑制细胞活性（SIHA细胞的IC50为465.25μM，HELA细胞的IC50为246.909μM），抑制细胞迁移、侵袭和增殖，诱导凋亡，并通过浓度依赖性方式逆转LOXL2诱导的上皮-间质转化（EMT）过程，从而抑制恶性转化[5]。(2-Chloropyridin-4-yl)methanamine hydrochloride（50nM；12h）处理Huh7和Hep3B细胞显著上调FBP1表达，下调Snail、HIF-1α和VEGF表达，并抑制细胞增殖、糖酵解和血管生成[6]。
在体内，在Angiotensin II诱导的心房颤动（AF）小鼠模型中，(2-Chloropyridin-4-yl)methanamine hydrochloride（100μg/kg/天；腹腔注射；4 周）显著减少了心房纤维化和心房颤动易感性，减轻了心房炎症和心肌肥大，并逆转了TGF-β1/Smad2/3信号通路激活和胶原蛋白I的表达[7]。