PXS-5120A
目录号 : GC63158
PXS-5120A 是一种有效的，不可逆的 Lysyl Oxidase-like 2/3 (LOXL2/3) 的氟代烯丙胺抑制剂，具有抗纤维化活性。与 LOXL (pIC50 为 5.8) 相比，PXS-5120A 对 LOXL2 (Ki 为 83 nM; pIC50 为 8.4) 的选择性高 300 倍以上。
Cas No.:2125955-70-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
PXS-5120A is a potent, irreversible fluoroallylamine inhibitor of Lysyl Oxidase-like 2/3 (LOXL2/3) with anti-fibrotic activity. PXS-5120A is >300-fold selective for LOXL2 (Ki of 83 nM; pIC50 of 8.4) over LOXL (pIC50 of 5.8)[1].
PXS-5120A (Compound 12k) is a potent inhibitor of the LOXL2/3 enzyme and a moderate blocker of LOXL4. PXS-5120A inhibits recombinant human LOXL2, human fibroblast LOXL2, recombinant mouse LOXL2, recombinant rat LOXL2, collagen oxidation assay, recombinant human LOXL3 and recombinant human LOXL4 with IC50s of 5 nM, 9 nM, 6 nM, 6 nM, 13 nM, 16 nM and 280 nM, respectively.
PXS-5129A is readily absorbed following oral gavage, and once in the circulation, rapidly hydrolyzed to release PXS-5120 (free base) in vivo, affording plasma concentrations well above the LOXL2 IC50 (6 nM) for a prolonged period (>6 h) in mice, while remaining well below the IC50 for LOX throughout[1].
[1]. Identification and Optimization of Findlay AD, et al. Mechanism-Based Fluoroallylamine Inhibitors of Lysyl Oxidase-like 2/3. J Med Chem. 2019 Nov 14;62(21):9874-9889.
| Cas No. | 2125955-70-4 | SDF | |
| 分子式 | C22H25ClFN3O4S | 分子量 | 481.97 |
| 溶解度 | 储存条件 | ||
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0748 mL | 10.3741 mL | 20.7482 mL |
| 5 mM | 0.415 mL | 2.0748 mL | 4.1496 mL |
| 10 mM | 0.2075 mL | 1.0374 mL | 2.0748 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Identification and Optimization of Mechanism-Based Fluoroallylamine Inhibitors of Lysyl Oxidase-like 2/3
J Med Chem 2019 Nov 14;62(21):9874-9889.PMID:31580073DOI:10.1021/acs.jmedchem.9b01283.
Lysyl oxidase-like 2 (LOXL2) is a secreted enzyme that catalyzes the formation of cross-links in extracellular matrix proteins, namely, collagen and elastin, and is indicated in fibrotic diseases. Herein, we report the identification and subsequent optimization of a series of indole-based fluoroallylamine inhibitors of LOXL2. The result of this medicinal chemistry campaign is PXS-5120A (12k), a potent, irreversible inhibitor that is >300-fold selective for LOXL2 over LOX. PXS-5120A also shows potent inhibition of LOXL3, an emerging therapeutic target for lung fibrosis. Key to the development of this compound was the utilization of a compound oxidation assay. PXS-5120A was optimized to show negligible substrate activity in vitro for related amine oxidase family members, leading to metabolic stability. PXS-5120A, in a pro-drug form (PXS-5129A, 12o), displayed anti-fibrotic activity in models of liver and lung fibrosis, thus confirming LOXL2 as an important target in diseases where collagen cross-linking is implicated.