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.