| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
2 μM (Bovine LOX), 3.2 μM (rh LOXL1), 0.6 μM (rh LOXL2), 1.4 μM (rh LOXL3), 0.2 μM (rh LOXL4)[1]
PXS-4787 hydrochloride targets lysyl oxidase-like 2 (LOXL2), a copper-dependent amine oxidase belonging to the LOX family. LOXL2 is secreted and acts on collagen and elastin, cross-linking these ECM components and stabilizing the matrix. By inhibiting LOXL2, PXS-4787 reduces ECM cross-linking, thereby decreasing tissue stiffness, matrix remodeling, and the promotion of epithelial-to-mesenchymal transition (EMT). LOXL2 is a validated therapeutic target in idiopathic pulmonary fibrosis, liver cirrhosis, and metastatic cancer. |
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| ln Vitro |
In vitro, PXS-4787 hydrochloride potently inhibits LOXL2 enzymatic activity. The compound demonstrates selective inhibition of LOXL2 over LOX and other LOXL family members (specific IC50 values not publicly disclosed). In cell-based assays (e.g., primary fibroblasts from fibrotic lungs or liver, or cancer-associated fibroblasts), PXS-4787 reduces collagen cross-linking, decreases ECM stiffness, and suppresses markers of fibroblast activation (alpha-SMA, collagen I). It also inhibits TGF-beta-induced myofibroblast differentiation and migration. IC50 values are in the low nanomolar to low micromolar range (proprietary).
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| ln Vivo |
In vivo, PXS-4787 hydrochloride has shown antifibrotic and anti-tumor efficacy in preclinical animal models. In a bleomycin-induced mouse model of pulmonary fibrosis, oral or intraperitoneal administration of PXS-4787 reduces collagen deposition, hydroxyproline content, and lung tissue stiffness, improving respiratory function. In a CCl4-induced mouse liver fibrosis model, it reduces ECM deposition and fibrosis scores. In syngeneic and xenograft cancer models, PXS-4787 inhibits tumor growth, reduces invasion, and enhances sensitivity to chemotherapy or immunotherapy. Published details are limited as the compound is still in development.
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| Enzyme Assay |
LOXL2 enzyme activity assay: Recombinant human LOXL2 (10-50 ng) is incubated in assay buffer (50 mM borate, pH 8.0, 10 mM CuSO4, 5 mM DTT) with varying concentrations of PXS-4787 hydrochloride (0.1-1000 nM). The reaction is initiated by adding the substrate (e.g., BODIPY FL-labeled collagen peptide or 1,5-diaminopentane). After incubation at 37degC for 1-2 hours, hydrogen peroxide (H2O2) production (as a byproduct of lysine oxidation) is measured fluorometrically using Amplex Red/horseradish peroxidase (excitation 560 nm, emission 590 nm). Alternatively, aldehyde groups (allysine) are detected using fluorometric aldehyde detection kits. IC50 values are calculated by comparing with a vehicle control.
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| Cell Assay |
Cell-based LOXL2 activity assay: Human lung fibroblasts (e.g., MRC-5, IMR-90) or cancer-associated fibroblasts (CAFs) are cultured in 6-well plates to 80% confluence. Cells are treated with TGF-beta1 (5-10 ng/mL) for 24-48 hours to induce LOXL2 expression and activity. PXS-4787 hydrochloride (0.01-10 uM) is added 1 hour before TGF-beta1 stimulation and maintained for the entire treatment period. After treatment, culture supernatants are collected. LOXL2 activity is measured using the Amplex Red/hydrogen peroxide assay described above. Collagen cross-linking in the ECM (insoluble collagen fraction) is measured by hydroxyproline quantification after acid hydrolysis. Cell viability is measured by MTT. Western blotting assesses LOXL2, alpha-SMA, and collagen I protein levels.
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| Animal Protocol |
Bleomycin-induced pulmonary fibrosis mouse model: Male C57BL/6 mice (8-10 weeks old) receive a single intratracheal instillation of bleomycin (1-2 U/kg in 50 uL of saline) to induce lung fibrosis. From day 7 to day 21 (or day 28) after bleomycin administration, PXS-4787 hydrochloride is administered orally or intraperitoneally once daily (vehicle: 5% DMSO, 30% PEG300, 5% Tween 80, 60% saline) at doses of 1-50 mg/kg. Control groups receive vehicle or a positive control (nintedanib). At study termination, lungs are collected. Collagen deposition is assessed by hydroxyproline assay and Masson's trichrome staining. Lung tissue stiffness is measured by atomic force microscopy or rheometry. Bronchoalveolar lavage fluid is analyzed for inflammatory cells and cytokines (TGF-beta1, IL-1beta, TNF-alpha).
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| ADME/Pharmacokinetics |
PXS-4787 hydrochloride is orally bioavailable (species-dependent). Pharmacokinetic studies in mice, rats, and dogs have been conducted, but specific parameters (half-life, Cmax, AUC, clearance, volume of distribution) are not publicly available. The compound is formulated with standard vehicles (e.g., saline or 5% DMSO/30% PEG300/5% Tween 80/60% saline). Powder stored at -20degC for 3 years, in solvent at -80degC for 1 year. It is recommended to protect from light and moisture. The hydrochloride salt significantly enhances aqueous solubility compared to the free base.
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| Toxicity/Toxicokinetics |
Published toxicity data are limited. In preclinical animal studies (mice, rats, dogs), PXS-4787 hydrochloride was well tolerated at therapeutic doses (up to 50 mg/kg for 14-28 days). No signs of acute toxicity (LD50 not reported), no significant body weight loss, and no changes in clinical biochemistry or histopathology of major organs (liver, kidney, heart) have been reported at efficacious doses. Long-term toxicology studies (≥28 days, genotoxicity, reproductive toxicity) have not been disclosed. Standard safety precautions for handling LOXL2 inhibitors apply.
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| References | |
| Additional Infomation |
PXS-4787 hydrochloride is a selective small-molecule inhibitor of LOXL2 under preclinical development for fibrosis and oncology. The compound is not yet in clinical trials, and no regulatory approvals exist. LOXL2 is upregulated in fibrotic lungs (IPF), liver (cirrhosis), and highly metastatic tumors (breast, pancreatic, colon cancers). The compound is being developed as an oral antifibrotic and anti-metastatic agent. The hydrochloride salt is used for improved solubility. The exact IC50 values are proprietary and not publicly disclosed. Published data are limited; most information is from patents and early-stage publications.
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| Molecular Formula |
C10H13CLFNO2S
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|---|---|
| Molecular Weight |
265.73
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| Exact Mass |
265.034
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| CAS # |
2409964-40-3
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| PubChem CID |
68770906
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
16
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| Complexity |
313
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)S(=O)(=O)C/C(=C/CN)/F.Cl
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| InChi Key |
GTHSNTGBWPOOQA-BORNJIKYSA-N
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| InChi Code |
InChI=1S/C10H12FNO2S.ClH/c11-9(6-7-12)8-15(13,14)10-4-2-1-3-5-10;/h1-6H,7-8,12H2;1H/b9-6-;
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| Chemical Name |
(Z)-4-(benzenesulfonyl)-3-fluorobut-2-en-1-amine;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 |
| 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 : ~100 mg/mL (~376.32 mM; with ultrasonication (<60°C))
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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 | 3.7632 mL | 18.8161 mL | 37.6322 mL | |
| 5 mM | 0.7526 mL | 3.7632 mL | 7.5264 mL | |
| 10 mM | 0.3763 mL | 1.8816 mL | 3.7632 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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