| Size | Price | |
|---|---|---|
| 100mg | ||
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Lysyl oxidase-like 2 (LOXL2) and lysyl oxidase-like 3 (LOXL3) enzymes.
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|---|---|
| ln Vitro |
For LOXL2, PXS-5153A has an IC50 of less than 40 nM in every tested mammalian species. Moreover, PXS-5153A inhibits human LOXL3 at an IC50 of 63 nM. PXS-5153A is 700 times more selective than other related amine oxidases and 40 times more selective for LOXL2 than LOX and LOXL1. PXS-5153A is classified as a fast-acting inhibitor because it blocks enzyme activity almost entirely in 15 minutes [1].
PXS-5153A inhibits LOXL2 with an IC50 of <40 nM across all mammalian species tested and human LOXL3 with an IC50 of 63 nM. It is >40-fold selective for LOXL2 over LOX and LOXL1 and >700-fold selective over other related amine oxidases. PXS-5153A is a fast-acting inhibitor with enzymatic activity almost entirely blocked within 15 minutes. |
| ln Vivo |
Collagen oxidation was, as predicted, dose-dependently enhanced by rhLOXL2 and dose-dependently inhibited by PXS-5153A. When PXS-5153A was administered to animals instead of CCl4, the amount of immature cross-links that formed was dramatically decreased. Treatment with PXS-5153A also decreases the development of mature cross-links. When compared to mice treated with CCl4, all PXS-5153A-treated groups exhibited a significant decrease in DHLNL development. HYP was significantly lower in the PXS-5153A group than in the CCl4 group. Additionally, diseases cause a considerable rise in fibrillar collagen, as evidenced by a 2.2-fold increase in the percentage of the covered area when stained with Sirius red, and a decrease in the same proportion when stained with PXS-5153A [1].
PXS-5153A dose-dependently reduces LOXL2-mediated collagen oxidation and collagen crosslinking in vitro. In two liver fibrosis models, therapeutic treatment substantially reduces immature crosslink formation, mature crosslink formation, and DHLNL formation compared with CCl4-treated animals. It also improves cardiac output in myocardial infarction models. |
| Enzyme Assay |
The enzymatic assay for LOXL2/LOXL3 uses recombinant enzyme and a fluorogenic or chromogenic substrate. Test compounds are incubated with the enzyme and substrate, and enzyme activity is measured by monitoring the release of product using a fluorescence or absorbance plate reader. IC50 values are determined from dose-response curves.
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| Cell Assay |
In cellular assays, fibroblasts or hepatic stellate cells are treated with PXS-5153A. LOXL2-mediated collagen oxidation and crosslinking are assessed using biochemical assays. Collagen deposition is measured by Sirius Red staining or hydroxyproline quantification to confirm antifibrotic activity.
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| Animal Protocol |
In vivo studies use liver fibrosis models (CCl4-induced) and myocardial infarction models. PXS-5153A is administered orally, and collagen crosslink formation is assessed in tissue samples. Liver function, collagen content, and cardiac output are measured to evaluate therapeutic efficacy.
|
| References |
| Molecular Formula |
C20H25CL2FN4O2S
|
|---|---|
| Molecular Weight |
475.407504796982
|
| Exact Mass |
474.105
|
| CAS # |
2125956-82-1
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| Related CAS # |
PXS-5153A monohydrochloride
|
| PubChem CID |
130302686
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| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
30
|
| Complexity |
664
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(C2=C(N1C/C(=C/CN)/F)C=CC=N2)C3=CC(=CC=C3)S(=O)(=O)N(C)C.Cl.Cl
|
| InChi Key |
INSNGJNTNAUITD-ULPVBNQHSA-N
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| InChi Code |
InChI=1S/C20H23FN4O2S.2ClH/c1-14-19(15-6-4-7-17(12-15)28(26,27)24(2)3)20-18(8-5-11-23-20)25(14)13-16(21)9-10-22;;/h4-9,11-12H,10,13,22H2,1-3H3;2*1H/b16-9-;;
|
| Chemical Name |
3-[1-[(Z)-4-amino-2-fluorobut-2-enyl]-2-methylpyrrolo[3,2-b]pyridin-3-yl]-N,N-dimethylbenzenesulfonamide;dihydrochloride
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.1034 mL | 10.5172 mL | 21.0345 mL | |
| 5 mM | 0.4207 mL | 2.1034 mL | 4.2069 mL | |
| 10 mM | 0.2103 mL | 1.0517 mL | 2.1034 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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