PAT-1251是一种赖氨酰氧化酶样蛋白2（LOXL2；IC50=0.71μM）抑制剂。
Cas No.:2098884-53-6
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | Mouse glomerular endothelial cells (mGECs) and primary human renal glomerular endothelial cells |
Preparation Method | Endothelial cells were seeded at a density of 2x106 cells/mL in 6-well plates and exposed to high glucose (HG; 30mM) for 24 hours. After the HG treatment, the cells were incubated with PAT-1251 (10µM) for an additional 24 hours. The conditioned medium (CM) from these treated endothelial cells was then collected, clarified, and applied to mouse glomerular mesangial cells to model intercellular crosstalk. |
Reaction Conditions | 10µM; 24h. |
Applications | The conditioned medium from high glucose-exposed endothelial cells treated with PAT-1251 (HG+PAT-1251-CM) significantly suppressed high glucose-induced mesangial cell proliferation/viability. PAT-1251 also reduced oxidative stress markers (malondialdehyde and protein carbonyl content) and attenuated the mRNA upregulation of pro-fibrotic genes (FN1, Col4a1) and collagen deposition in mesangial cells. |
| Animal experiment [2]: | |
Animal models | Male Wistar rats |
Preparation Method | In the rat models, animals were randomized to receive either the LOXL2 inhibitor PAT-1251 or no treatment. PAT-1251 was prepared in 0.5% methylcellulose and administered by oral gavage (30mg/kg) under light anesthesia, five times per week for 3 weeks, starting on the day of PH induction. |
Dosage form | 30mg/kg; oral gavage; five times per week for 3 weeks. |
Applications | PAT-1251 treatment significantly ameliorated PH. PAT-1251 reduced systolic and mean pulmonary artery pressures, decreased pulmonary arterial elastance, and improved right ventricular function (assessed by pressure-volume loops). Treatment also improved survival. |
References: | |
| Cas No. | 2098884-53-6 | SDF | |
| Canonical SMILES | O=C(C1=CC=CC(OC2=NC(C(F)(F)F)=CC(CN)=C2)=C1)N3C[C@@H](F)[C@H](O)C3.Cl | ||
| 分子式 | C18H18ClF4N3O3 | 分子量 | 435.8 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2946 mL | 11.4732 mL | 22.9463 mL |
| 5 mM | 458.9 μL | 2.2946 mL | 4.5893 mL |
| 10 mM | 229.5 μL | 1.1473 mL | 2.2946 mL |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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