| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Autotaxin modulator 1 is an enzyme inhibitor that blocks autotaxin activity, reducing the production of lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). LPA is a bioactive lipid signaling molecule that activates multiple G protein-coupled receptors (LPAR1-6) involved in inflammatory responses, cancer progression, angiogenesis, and fibrosis. By inhibiting ATX, this compound effectively disrupts the ATX-LPA signaling axis.
|
|---|---|
| ln Vitro |
Autocrine motility protein is a new type of motility inducing protein. It is a secreted glycoprotein commonly prevalent in biological fluids such as blood, cancer ascites, synovial fluid, pleura and cerebrospinal fluid. It was originally produced from melanoma cells as an autocrine motility inducing factor. separated from the supernatant [1]. Autocrine motility factor is a member of the extracellular nucleotide pyrophosphatase/phosphodiesterase family (E-NPP), which hydrolyzes the phosphodiesterase (PDE) linkages of different nucleotides and derivatives [1].
In vitro studies demonstrate that Autotaxin modulator 1 functions as a potent autotaxin (ATX) enzyme inhibitor. The compound inhibits ATX-mediated conversion of LPC to LPA, thereby reducing LPA production in cell-free enzymatic assays. Autotaxin is a secreted glycoprotein widely present in biological fluids including blood, cancer ascites, synovial fluid, pleural fluid, and cerebrospinal fluid. It was originally identified as an autocrine motility-stimulating factor from melanoma cell supernatants. In vitro assays typically measure the inhibition of ATX enzymatic activity using fluorescent or chromogenic substrates. |
| ln Vivo |
In vivo studies with Autotaxin modulator 1 have been conducted in animal models of demyelination and cancer. By inhibiting ATX activity and reducing LPA production, the compound modulates inflammatory responses, tumor progression, and fibrotic processes. It is expected to be useful for researching demyelination due to injury or disease, as well as proliferative disorders such as cancer. The compound's in vivo efficacy has been evaluated in various preclinical disease models to validate the therapeutic potential of targeting ATX-mediated processes in oncology, immunology, and fibrotic diseases.
|
| Enzyme Assay |
In vitro enzyme assays for Autotaxin modulator 1 typically measure the inhibition of ATX enzymatic activity. The assay is performed using recombinant human autotaxin enzyme and a fluorescent substrate such as bis-p-nitrophenyl phosphate or FS-3. The compound is serially diluted in assay buffer and pre-incubated with the enzyme for 15-30 minutes at 37degC. The substrate is then added, and the reaction is allowed to proceed for 1-2 hours. Fluorescence is measured at appropriate excitation/emission wavelengths (typically Ex/Em = 485/530 nm for FS-3). IC50 values are calculated from dose-response curves using nonlinear regression analysis. Positive controls (known ATX inhibitors) and negative controls (vehicle) are included in each assay run.
|
| Cell Assay |
In vitro cell-based assays for Autotaxin modulator 1 typically use cancer cell lines or primary cells that express autotaxin and respond to LPA stimulation. Cells are cultured in appropriate media and treated with varying concentrations of the compound for 24-72 hours. Cellular responses measured include cell proliferation (MTT or CCK-8 assays), migration (transwell or scratch assays), and invasion (Matrigel invasion assays). LPA-induced signaling pathways (e.g., ERK, Akt phosphorylation) can be assessed by Western blotting. The compound's effect on autotaxin expression and secretion can be measured by ELISA or Western blot of conditioned media.
|
| Animal Protocol |
In vivo animal studies for Autotaxin modulator 1 are conducted in rodent models of disease. A typical protocol involves oral or intraperitoneal administration of the compound at doses ranging from 1-30 mg/kg, daily or twice daily, for 1-4 weeks depending on the study design. In cancer models, tumor volume and weight are measured, and tumor tissues are analyzed for LPA levels, cell proliferation markers (Ki-67), and apoptosis (TUNEL). In demyelination models, neurological function and myelination status are assessed. Plasma and tissue samples are collected for pharmacokinetic analysis and biomarker evaluation.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Autotaxin modulator 1 (compound 12b) are consistent with small-molecule drug candidates. The compound has a molecular weight of 543.54 and a calculated LogP of approximately 6.25, indicating high lipophilicity. It contains six fluorine atoms, which may contribute to metabolic stability and improved pharmacokinetic properties. The compound is expected to have good oral bioavailability based on its physicochemical properties. It is typically formulated in DMSO for in vitro studies and in suitable vehicles (e.g., PEG400, saline) for in vivo administration. Plasma protein binding and metabolic stability can be assessed using standard in vitro assays with liver microsomes.
|
| Toxicity/Toxicokinetics |
Toxicological data for Autotaxin modulator 1 are limited to preclinical research studies. As a research-use compound, comprehensive toxicity profiles are not extensively documented. Standard safety precautions for handling chemical compounds apply, including the use of appropriate personal protective equipment and working in a fume hood. The compound is intended for research purposes only and not for human therapeutic use. Acute toxicity, genotoxicity, and chronic toxicity studies have not been systematically reported for this research compound. Proper storage at -20degC in a desiccated environment is recommended to maintain stability.
|
| References | |
| Additional Infomation |
Autotaxin modulator 1 is a research-grade compound identified as compound example 12b in patent WO 2014018881 A1. It is classified as an autotaxin (ATX) enzyme inhibitor applicable for studying demyelination and tumors. The compound has a purity of ≥95% and is supplied as a white to off-white solid powder. Its IUPAC name is 8-[(1R)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid. The compound is expected to be useful for researching demyelination due to injury or disease, as well as for researching proliferative disorders such as cancer. Not approved for clinical use.
|
| Molecular Formula |
C28H31F6NO3
|
|---|---|
| Molecular Weight |
543.54106926918
|
| Exact Mass |
543.22
|
| CAS # |
1548743-69-6
|
| PubChem CID |
90032900
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
586.9±50.0 °C at 760 mmHg
|
| Flash Point |
308.7±30.1 °C
|
| Vapour Pressure |
0.0±1.7 mmHg at 25°C
|
| Index of Refraction |
1.544
|
| LogP |
6.25
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
38
|
| Complexity |
827
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@H](C1=CC2=C(C=C1)C=CC(=C2C(F)(F)F)OC3CCC(CC3)C(F)(F)F)N4C5CCC4CC(C5)C(=O)O
|
| InChi Key |
PZASAAIJIFDWSB-WMHNCSEASA-N
|
| InChi Code |
InChI=1S/C28H31F6NO3/c1-15(35-20-7-8-21(35)13-18(12-20)26(36)37)17-3-2-16-4-11-24(25(23(16)14-17)28(32,33)34)38-22-9-5-19(6-10-22)27(29,30)31/h2-4,11,14-15,18-22H,5-10,12-13H2,1H3,(H,36,37)/t15-,18?,19?,20?,21?,22?/m1/s1
|
| Chemical Name |
8-[(1R)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~183.98 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.60 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 25.0 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: ≥ 2.5 mg/mL (4.60 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 25.0 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: ≥ 2.5 mg/mL (4.60 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 | 1.8398 mL | 9.1990 mL | 18.3979 mL | |
| 5 mM | 0.3680 mL | 1.8398 mL | 3.6796 mL | |
| 10 mM | 0.1840 mL | 0.9199 mL | 1.8398 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
