PAT-1251 is a lysyl oxidase-like 2 (LOXL2; IC50=0.71μM) inhibitor[1-2]. PAT-1251 can reduce collagen cross-linking and fibrosis by inhibiting LOXL2. PAT-1251 can be used for related research on fibrotic diseases and cancer metastasis[3].
In vitro, PAT-1251 (10μM) was co-treated with TGF-β1 on 3D ring-shaped tissues derived from human fibroblasts for 14 days, significantly reducing TGF-β1-induced tissue strength and stiffness without altering collagen levels[4]. PAT-1251 (10μM) was used to treat glomerular endothelial cells cultured under high glucose (30mM) conditions for 24 hours, and the conditioned medium was collected. When this conditioned medium was applied to glomerular mesangial cells, PAT-1251 significantly inhibited high glucose-induced cell proliferation/viability, reduced oxidative stress markers, and decreased the expression of pro-fibrotic genes and collagen deposition[5].
In vivo, PAT-1251 (30mg/kg) was administered via oral gavage five times per week to treat rats with hypoxia-induced pulmonary hypertension for 3 weeks. PAT-1251 significantly improved pulmonary artery pressure, right ventricular remodeling, and survival rate in the rats[6].
References:
[1] Rowbottom MW, Bain G, Calderon I, et al. Identification of 4-(Aminomethyl)-6-(trifluoromethyl)-2-(phenoxy)pyridine Derivatives as Potent, Selective, and Orally Efficacious Inhibitors of the Copper-Dependent Amine Oxidase, Lysyl Oxidase-Like 2 (LOXL2). J Med Chem. 2017 May 25;60(10):4403-4423.
[2] Cetin M, Saatci O, Rezaeian AH, et al. A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer. Cell Chem Biol. 2024 Nov 21;31(11):1926-1941.e11.
[3] Hu Y, Wang Y, Tan W, et al. Design and Optimization of LOXL2 and sGC Dual-Target Regulators Targeting Extracellular Matrix Dysregulation and Vasodilation for the Treatment of Pulmonary Arterial Hypertension. J Med Chem. 2025 Dec 25;68(24):26547-26573.
[4] Wu Y, Millender J, Padgett B, et al. An in vitro model to measure the strength and stiffness of the extracellular matrix synthesized de novo by human fibroblasts. In Vitro Model. 2025 Mar 7;4(1):59-69.
[5] Kang T, Hou B, Shi M, et al. Verbascoside targets endothelial HIF-1α/ Lysyl oxidase signaling to attenuate glomerular injury in diabetic nephropathy. Redox Rep. 2025 Dec;30(1):2598110.
[6] Steppan J, Wang H, Nandakumar K, et al. LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2024 Oct 1;327(4):L423-L438.
PAT-1251是一种赖氨酰氧化酶样蛋白2（LOXL2；IC50=0.71μM）抑制剂[1-2]。PAT-1251可通过抑制LOXL2来减少胶原交联和纤维化。PAT-1251可用于纤维性疾病和癌症转移的相关研究[3]。
在体外，PAT-1251(10μM)与TGF-β1共处理人成纤维细胞来源的3D环状组织14天。PAT-1251可显著降低由TGF-β1诱导的环状组织强度与刚度，且不改变胶原蛋白水平[4]。PAT-1251（10μM）处理高糖（30mM）条件下培养的肾小球内皮细胞24小时，收集培养基。该条件培养基作用于肾小球系膜细胞时，可显著抑制高糖诱导的细胞增殖/活力，并降低氧化应激标志物和促纤维化基因的表达及胶原沉积[5]。
PAT-1251(30mg/kg)通过口服灌胃给药，每周五次，持续3周，用于处理低氧诱导的肺高血压模型大鼠。PAT-1251显著改善了大鼠的肺动脉压力、右心室重塑情况和大鼠生存率[6]。