| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
pKi: 8.4 (Lysyl Oxidase-like 2) and 5.8 (Lysyl Oxidase-like); Ki: 83 nM (Lysyl Oxidase-like 2)[1]
LOXL2 (lysyl oxidase-like 2) and LOXL3 (lysyl oxidase-like 3); also inhibits LOXL4 to a moderate extent. |
|---|---|
| ln Vitro |
Compound 12k, or PXS-5120A, is a moderate blocker of LOXL4 and a strong inhibitor of LOXL2/3. With IC50s of 5 nM, 9 nM, 6 nM, 6 nM, 13 nM, 16 nM, and 280 nM, respectively, 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.
PXS-5120A is a potent inhibitor of LOXL2 with a Ki of 83 nM and a pIC50 of 8.4. It is >300-fold selective for LOXL2 over LOX (pIC50 = 5.8). It also shows potent inhibition of LOXL3, an emerging therapeutic target for lung fibrosis. This high selectivity and potency make it a valuable tool for studying LOXL2/3-specific functions. |
| ln Vivo |
PXS-5129A is quickly absorbed after oral gavage, quickly hydrolyzes once in the bloodstream to release PXS-5120 (free base), and provides plasma concentrations in mice that are significantly higher than the LOXL2 IC50 (6 nM) for an extended length of time (>6 h), all the while staying well below the IC50 for LOX[1].
As a potent and selective LOXL2/3 inhibitor, PXS-5120A is used in in vivo models to study the role of these enzymes in fibrosis. Its anti-fibrotic activity has been demonstrated, making it a promising candidate for the treatment of fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). |
| Enzyme Assay |
In vitro enzyme assays are performed to characterize the inhibitory activity of PXS-5120A against LOXL2, LOXL3, and LOX. The enzymes are incubated with their substrates and varying concentrations of the compound. The inhibition of enzyme activity is measured, and Ki or IC50 values are calculated from the data. The selectivity profile is determined by comparing the compound's activity against different LOX family members.
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| Cell Assay |
Cells expressing LOXL2 or LOXL3 (e.g., fibroblasts) are treated with PXS-5120A to assess its cellular effects. The compound's ability to inhibit LOX activity and collagen crosslinking in cells is measured. Its effects on cell signaling, migration, and extracellular matrix production are also evaluated to understand its anti-fibrotic mechanism.
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| Animal Protocol |
In vivo studies are conducted in animal models of fibrosis, such as the bleomycin-induced lung fibrosis model, to evaluate the therapeutic potential of PXS-5120A. The compound is typically administered via oral or parenteral routes. Its effects on collagen deposition, tissue architecture, and functional outcomes are assessed.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are publicly available for PXS-5120A. As a potent and selective inhibitor with anti-fibrotic activity, its ADME properties would be studied to support in vivo efficacy studies. Its oral bioavailability and tissue distribution are key parameters for its development.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available. As an irreversible LOXL2/3 inhibitor, its toxicity profile would be evaluated in standard preclinical studies. On-target toxicity related to the essential role of LOX family enzymes in connective tissue maintenance is a potential concern that would be carefully assessed.
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| References | |
| Additional Infomation |
PXS-5120A is a highly selective and potent LOXL2/3 inhibitor with significant anti-fibrotic potential. Its discovery represents a major advance in the development of targeted therapies for fibrotic diseases. It is not approved for clinical use and is currently a research tool. Its high selectivity over LOX is a key feature that may reduce on-target side effects.
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| Molecular Formula |
C22H25CLFN3O4S
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|---|---|
| Molecular Weight |
481.9680
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| Exact Mass |
481.123
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| CAS # |
2125955-70-4
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| PubChem CID |
130302628
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
782
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].S(C1=C([H])C([H])=C([H])C(=C1[H])C1=C(C([H])([H])[H])N(C([H])([H])/C(=C(\[H])/C([H])([H])N([H])[H])/F)C2C([H])=C([H])C(C(=O)O[H])=C([H])C1=2)(N(C([H])([H])[H])C([H])([H])[H])(=O)=O
|
| InChi Key |
PWSRWJMEGVKWES-WPTDRQDKSA-N
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| InChi Code |
InChI=1S/C22H24FN3O4S.ClH/c1-14-21(15-5-4-6-18(11-15)31(29,30)25(2)3)19-12-16(22(27)28)7-8-20(19)26(14)13-17(23)9-10-24;/h4-9,11-12H,10,13,24H2,1-3H3,(H,27,28);1H/b17-9-;
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| Chemical Name |
1-[(Z)-4-amino-2-fluorobut-2-enyl]-3-[3-(dimethylsulfamoyl)phenyl]-2-methylindole-5-carboxylic acid;hydrochloride
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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 (259.35 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0748 mL | 10.3741 mL | 20.7482 mL | |
| 5 mM | 0.4150 mL | 2.0748 mL | 4.1496 mL | |
| 10 mM | 0.2075 mL | 1.0374 mL | 2.0748 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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