| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Autotaxin:8.8 nM (IC50)
S32826 primarily targets autotaxin (ATX/ENPP2), the enzyme responsible for the majority of extracellular LPA production. It inhibits ATX with an IC50 of 8.8-9 nM, demonstrating similar potency against all three ATX isoforms (α, β, and γ). S32826 exhibits no significant affinity for the lysophosphatidic acid receptor 1 (LPA1) at concentrations up to 10 μM, confirming its specificity as an enzyme inhibitor rather than a receptor antagonist. It shows much reduced activity against other targets such as Src (IC50 ~6 µM) and PTP-1B (IC50 ~15 µM), and little activity toward 29 other receptors and enzymes. By inhibiting ATX, S32826 effectively blocks the production of LPA, thereby modulating LPA-mediated signaling pathways involved in cell proliferation, migration, survival, and inflammation. |
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| ln Vitro |
S32826 (0.001-10 μM; 10 days) disodium inhibits 3T3-F442A adipocytes' release of lyso-phosphatidic acid (LPA) in a dose-dependent manner, with an IC50 of 90 nM and a peak inhibition of 80% at 500 nM[1]. The dexamethasone-induced increases in autotaxin (ATX) mRNA expression in HTM cells, lysoPLD activity in conditioned media, and expression of α-SMA, fibronectin, and collagen-1 in the HTM cells are all inhibited by S32826 (1 μM; 24 h) disodium[2].
S32826 demonstrates potent in vitro activity by inhibiting the enzymatic activity of autotaxin. In enzyme assays using ATX beta, it inhibits phosphodiesterase activity with an IC50 of 9 nM in the pNppp assay and lysoPLD activity with IC50 values of 5.6 nM and 47 nM, depending on the detection method (enzyme-linked fluorescence or autoradiography by TLC, respectively). In cell-based assays, S32826 inhibits LPA release from murine 3T3-F442A adipocytes in a dose-dependent manner with an IC50 of 90 nM and a peak inhibition of 80% at 500 nM. Furthermore, at 1 μM, S32826 inhibits dexamethasone-induced increases in autotaxin mRNA expression, lysoPLD activity, and the expression of α-SMA, fibronectin, and collagen-1 in human trabecular meshwork (HTM) cells. S32826 also inhibits LPA release from excised human and rat adipose tissues by approximately 70% at 0.2 and 1 µM, respectively, in ex vivo cultures. |
| ln Vivo |
Intraocular pressure (IOP) is lowered in rabbits by topical administration of S32826 (2-10 mM; 2 h-5 d) disodium in a dose- and time-dependent manner[2]. Rabbits' IOP is lowered by S32826 (∼2 µM; single intracameral injection), and the ocular hypotensive reaction lasts for almost 48 hours[2]. The disodium S32826 (10 mg/kg; po, ip, sc, and iv) exhibits low bioavailability and/or in vivo stability[1].
In vivo studies have demonstrated that S32826 can lower intraocular pressure (IOP) in rabbits. Topical administration of S32826 (2-10 mM) reduces IOP in a dose- and time-dependent manner. A single intracameral injection of S32826 (~2 µM) also lowers IOP in rabbits, with the ocular hypotensive response lasting for almost 48 hours. These findings suggest a role for the ATX-LPA axis in regulating IOP. However, the in vivo applicability of S32826 is significantly limited by its poor pharmacokinetic properties. Studies have shown that S32826 exhibits low bioavailability and/or in vivo stability when administered via oral, intraperitoneal, subcutaneous, or intravenous routes. This limitation restricts its use primarily to in vitro and ex vivo studies. |
| Enzyme Assay |
S32826 is a phosphonate compound that potently inhibits both the phosphodiesterase and lysoPLD activities of ATX. The in vitro enzyme assay for S32826 typically involves measuring its inhibition of ATX beta using the pNppp (p-nitrophenylphosphorylcholine) substrate for phosphodiesterase activity or using a fluorescent LPC analog for lysoPLD activity. In the pNppp assay, the release of p-nitrophenol is measured spectrophotometrically. For lysoPLD activity, the release of fluorescently labeled choline or LPA is detected by enzyme-linked fluorescence or autoradiography following TLC separation. The IC50 values are determined from dose-response curves. It is noted that CTAB can counteract the inhibitory activity of S32826; therefore, 2-methyl-2,4-pentanediol is recommended as an alternative to stabilize purified enzyme in solution during S32826 inhibition assays.
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| Cell Assay |
S32826's in vitro cellular activity is assessed using adipocyte and other cell-based models. In a typical assay, murine 3T3-F442A adipocytes are differentiated and treated with S32826 at concentrations ranging from 0.001 to 10 µM for a specified period (e.g., 10 days). The release of lysophosphatidic acid (LPA) into the culture medium is then measured, and the IC50 for LPA release inhibition is determined (90 nM). In another cellular model using HTM cells, cells are treated with dexamethasone to induce ATX expression and fibrotic markers, in the presence or absence of S32826 (1 µM; 24 h). The effects on ATX mRNA expression (by qPCR), lysoPLD activity in conditioned media, and expression of α-SMA, fibronectin, and collagen-1 (by Western blot or qPCR) are assessed. These assays confirm S32826's ability to inhibit ATX activity and downstream fibrotic responses in cells.
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| Animal Protocol |
In vivo animal experiments for S32826 have been primarily conducted in rabbit models to study its effects on intraocular pressure (IOP). In one protocol, S32826 disodium is administered topically to the eyes of rabbits at concentrations ranging from 2 to 10 mM. IOP is measured at various time points (from 2 hours to 5 days) using a tonometer to assess the dose- and time-dependent hypotensive response. In another protocol, a single intracameral injection of S32826 (~2 µM) is administered, and IOP is monitored for up to 48 hours to evaluate the duration of the ocular hypotensive effect. Despite these positive efficacy findings, the compound's poor pharmacokinetic properties have limited its use in systemic in vivo models. Pharmacokinetic studies in rodents have shown that S32826 exhibits low bioavailability and/or in vivo stability when administered via various routes.
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| ADME/Pharmacokinetics |
S32826 has a molecular weight of 441.45 and a molecular formula of C21H34NNa2O4P. The compound is a white to off-white solid powder. Its pharmacokinetic properties are characterized by low epithelial permeability and poor bioavailability. Studies have shown that S32826 exhibits low bioavailability and/or in vivo stability when administered via oral (po), intraperitoneal (ip), subcutaneous (sc), and intravenous (iv) routes. The compound is hygroscopic and should be stored under an inert atmosphere. For research use, it is recommended to store the powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. S32826 is soluble in water at 0.5 mg/mL.
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| Toxicity/Toxicokinetics |
S32826 is a research compound and is not approved for any clinical or therapeutic use. As an inhibitor of autotaxin, it is primarily used as a pharmacological tool to study the ATX-LPA axis in various biological and disease models. Its toxicity profile has not been extensively characterized, but its use is limited to in vitro and ex vivo studies due to its poor pharmacokinetic properties. In cell-based assays, S32826 has been shown to effectively inhibit LPA release from adipocytes and modulate fibrotic responses in HTM cells at concentrations up to 1 µM without reported cytotoxicity. However, comprehensive toxicological data, including acute and chronic toxicity studies, are not available. As with all research chemicals, standard laboratory safety precautions should be followed when handling S32826.
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| References |
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| Additional Infomation |
S32826 is a potent and selective inhibitor of autotaxin (ATX), a key enzyme in the production of lysophosphatidic acid (LPA). By inhibiting ATX, S32826 blocks LPA production and thereby modulates LPA-mediated signaling pathways. Its discovery, synthesis, and applications as a pharmacological tool have been described in the literature. S32826 is used to study the role of the ATX-LPA axis in various pathologies, including cancer, fibrosis, inflammation, and metabolic diseases. However, its in vivo applicability is limited by poor pharmacokinetic properties, making it primarily suitable for in vitro and ex vivo studies. Despite this limitation, S32826 remains a valuable tool for validating ATX as a therapeutic target and for studying the biological functions of the ATX-LPA pathway.
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| Molecular Formula |
C21H34NNA2O4P
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|---|---|
| Molecular Weight |
441.45
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| Exact Mass |
441.202
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| CAS # |
1103672-43-0
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| Related CAS # |
S32826;1096770-84-1
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| PubChem CID |
71311878
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
29
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| Complexity |
418
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DGRFALMFDGBLCP-UHFFFAOYSA-L
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| InChi Code |
InChI=1S/C21H36NO4P.2Na/c1-2-3-4-5-6-7-8-9-10-11-12-13-21(23)22-20-16-14-19(15-17-20)18-27(24,25)26;;/h14-17H,2-13,18H2,1H3,(H,22,23)(H2,24,25,26);;/q;2*+1/p-2
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| Chemical Name |
disodium;N-[4-(phosphonatomethyl)phenyl]tetradecanamide
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| Synonyms |
S32826 S 32826 S-32826
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
Ethanol : ~2.4 mg/mL (~5.44 mM)
H2O : < 0.1 mg/mL |
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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 | 2.2653 mL | 11.3263 mL | 22.6526 mL | |
| 5 mM | 0.4531 mL | 2.2653 mL | 4.5305 mL | |
| 10 mM | 0.2265 mL | 1.1326 mL | 2.2653 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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