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| Targets |
PXS-5153A targets the enzymatic activity of lysyl oxidase-like 2 (LOXL2) and lysyl oxidase-like 3 (LOXL3). These enzymes catalyze the oxidative deamination of lysine residues in collagen and elastin, a critical step in extracellular matrix crosslinking. By inhibiting LOXL2/LOXL3, PXS-5153A reduces collagen crosslinking, which is implicated in fibrosis, cancer progression, and tissue remodeling.
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| ln Vitro |
For LOXL2, PXS-5153A monohydrochloride exhibits an IC50 of less than 40 nM in all tested mammalian species. With an IC50 of 63 nM, PXS-5153A monohydrochloride also inhibits human LOXL3. More than 700 times more selective than other comparable amine oxidases, PXS-5153A monohydrochloride is more than 40 times more selective for LOXL2 than LOX and LOXL1. The fast-acting inhibitor PXS-5153A monohydrochloride blocks enzyme activity almost entirely in 15 minutes [1].
In vitro, PXS-5153A exhibits an IC50 of <40 nM for LOXL2 across all mammalian species tested. It also inhibits human LOXL3 with an IC50 value of 63 nM. PXS-5153A is >40-fold selective for LOXL2 over both LOX and LOXL1 and >700-fold selective over other comparable amine oxidases. The compound is a fast-acting inhibitor, with enzymatic activity almost entirely blocked within 15 minutes. |
| ln Vivo |
PXS-5153A monohydrochloride dose-dependently inhibited collagen oxidation, whereas rhLOXL2 dose-dependently promoted it. When compared to animals treated with CCl4, treatment with PXS-5153A monohydrochloride dramatically decreased the production of immature cross-links. The treatment with PXS-5153A monohydrochloride also decreased the amount of mature cross-links that formed. When comparing the DHLNL formation of all groups receiving PXS-5153A monohydrochloride to the animals treated with CCl4, a substantial reduction was observed. When HYP was treated with PXS-5153A monohydrochloride, it was much lower than in the CCl4 group. Additionally, a 2.2-fold increase in the proportion of Sirius red stained area covered indicates that the disease considerably increases the amount of fibrillar collagen, whereas PXS-5153A decreases the area covered [1].
In vivo, rhLOXL2 dose-dependently induced oxidation of collagen with PXS-5153A dose-dependently impeding collagen oxidation. Therapeutic treatment of PXS-5153A substantially reduces immature crosslink formation compared with CCl4-treated animals. The compound is orally active, making it suitable for chronic administration in fibrotic disease models. |
| Enzyme Assay |
A cell-free LOXL2 enzyme inhibition assay is performed. Recombinant human LOXL2 (0.1-1 microg) is incubated with varying concentrations of PXS-5153A monohydrochloride (0.1-1000 nM) in assay buffer (50 mM borate, 1.2 M urea, pH 8.0) for 15 minutes at 37degC. The reaction is initiated by adding 10 microM BODIPY-FL-collagen substrate. Fluorescence increase (ex/em = 485/525 nm) is measured for 60 minutes. The IC50 is calculated by nonlinear regression.
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| Cell Assay |
Cells expressing LOXL2 (e.g., hepatic stellate cells or fibroblasts) are seeded in 96-well plates. After 24 hours, cells are treated with PXS-5153A monohydrochloride (0.1-100 nM) for 24-48 hours. LOXL2 activity is measured using an Amplex Red-based assay. Collagen crosslinking is assessed by HPLC analysis of hydroxylysine pyridinoline crosslinks. Cell viability is measured by MTT.
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| Animal Protocol |
The CCl4-induced mouse model of liver fibrosis is used. Male C57BL/6 mice are injected intraperitoneally with CCl4 (1 mL/kg, 1:4 in corn oil) twice weekly for 6 weeks. PXS-5153A monohydrochloride (30 mg/kg, suspended in 0.5% methylcellulose) is administered orally by gavage daily during the final 2 weeks. Liver tissues are collected. Hydroxyproline content is measured. Sirius Red staining quantifies collagen deposition. LOXL2 activity in tissue lysates is assessed.
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| ADME/Pharmacokinetics |
PXS-5153A monohydrochloride is orally active and has a molecular weight of 438.95. It is a fast-acting inhibitor, with enzymatic activity almost entirely blocked within 15 minutes. Detailed PK parameters (t½, Cmax, AUC, F) have not been fully reported. The monohydrochloride salt enhances aqueous solubility. The compound can be formulated in 0.5% methylcellulose for oral administration.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for PXS-5153A monohydrochloride. As a LOXL2/LOXL3 inhibitor, the primary mechanism-based safety concern is potential effects on normal extracellular matrix remodeling. In animal studies, the compound was well-tolerated at the doses used (30 mg/kg oral) without overt signs of toxicity. Formal toxicology studies have not been published.
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| References | |
| Additional Infomation |
PXS-5153A monohydrochloride is a research-grade compound and is not approved for clinical use. It is a potent, selective, orally active and fast-acting dual inhibitor of LOXL2/LOXL3. It represents a valuable tool for studying the role of LOXL2/LOXL3 in fibrosis and cancer. This product is for research use only and not for human therapeutic applications.
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| Molecular Formula |
C20H24CLFN4O2S
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| Molecular Weight |
438.95
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| Related CAS # |
PXS-5153A;2125956-82-1
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| Appearance |
Off-white to yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~125 mg/mL (~284.77 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2782 mL | 11.3908 mL | 22.7816 mL | |
| 5 mM | 0.4556 mL | 2.2782 mL | 4.5563 mL | |
| 10 mM | 0.2278 mL | 1.1391 mL | 2.2782 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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