| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ALK5 4.83 nM (IC50) p38α 1.5 μM (IC50)
EW-7195 targets activin receptor-like kinase 5 (ALK5, also known as TβRI), the type I receptor for TGF-β. ALK5 is a serine/threonine kinase that, upon TGF-β binding, phosphorylates SMAD2 and SMAD3, leading to their nuclear translocation and regulation of gene expression involved in fibrosis, EMT, and cancer progression. EW-7195 is a potent and selective ATP-competitive inhibitor of ALK5 with an IC₅₀ of 4.83 nM. By blocking ALK5 kinase activity, EW-7195 inhibits TGF-β1-induced Smad2 phosphorylation and subsequent nuclear translocation of the Smad2/3 complex. |
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| ln Vitro |
Breast cancer cells' EMT, motility, and invasiveness are all inhibited in vitro by EW7195. Effectively inhibiting TGF-β1-induced Smad2 phosphorylation and subsequent Smad2/3 nuclear translocation is EW-7195. TGF-β1-induced mesenchymal morphology is inhibited by EW-7195. TGF-β-induced transcriptional activation is inhibited by EW-7195[1]. TGF-β1-induced Smad2 phosphorylation is effectively inhibited by EW-7195 (0.5–1 µM; 1.5 hours)[1].
In vitro, EW-7195 inhibits ALK5 kinase with an IC₅₀ of 4.83 nM. It effectively blocks TGF-β1-induced Smad signaling. The compound inhibits TGF-β1-induced Smad2 phosphorylation and subsequent nuclear translocation of the Smad2/3 complex, thereby suppressing EMT. Luciferase reporter assays are widely used to study the activity of this pathway. EW-7195 has been shown to inhibit breast cancer metastasis to the lung in various mouse models. Its activity makes it a valuable tool for studying TGF-β signaling in fibrosis and cancer. |
| ln Vivo |
EW7195 (40 mg/kg; ip; three times a week for 3/2.5 weeks) prevents the growth of lung metastases in both MMTV/cNeu transgenic mice and 4T1 orthotopic xenograft mice[1].
In vivo, EW-7195 has been shown to inhibit breast cancer metastasis to the lung in various mouse models. The compound suppresses EMT and inhibits the metastatic spread of cancer cells. It has also been investigated for its effects on fibrosis and inflammation, including diabetic nephropathy. EW-7195 attenuates the progression of diabetic nephropathy in db/db mice through suppression of fibrogenesis and inflammation. Further in vivo studies are needed to fully characterize its efficacy and safety across different indications. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for EW-7195 typically involve kinase activity assays using purified ALK5 protein. The compound's ability to inhibit ALK5 kinase activity is assessed using radiometric or fluorescence-based kinase assays with appropriate peptide substrates. IC₅₀ values (4.83 nM) are determined through dose-response experiments. Selectivity against other kinases is confirmed through parallel kinase panel screening. The compound's ability to inhibit TGF-β1-induced Smad signaling is assessed in cell-based assays measuring SMAD2/3 phosphorylation by Western blot or using SMAD-responsive reporter gene assays.
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| Cell Assay |
In vitro cell-based assays for EW-7195 utilize cell lines that respond to TGF-β signaling. Cells are treated with varying concentrations of the compound for 24-48 hours, followed by stimulation with TGF-β1. TGF-β1-induced Smad2 phosphorylation is measured by Western blot. SMAD-responsive reporter gene assays using (CAGA)12-luciferase or similar constructs are employed to assess transcriptional activity. EMT markers such as E-cadherin and vimentin are assessed by Western blot or immunofluorescence. Cell migration and invasion assays can also be performed. Standard cell culture conditions (37°C, 5% CO₂) with appropriate media are employed.
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| Animal Protocol |
Animal/Disease Models: MMTV/c-Neu mice[1]
Doses: 40 mg/kg Route of Administration: Ip; three times a week for 3 weeks Experimental Results: Inhibited the metastasis of breast cancer cells to the lung. Animal/Disease Models: Balb/c xenograft model (10-weeks-old female balb/c (Bagg ALBino) mouse bearing 4T1 cells)[1] Doses: 40 mg/kg Route of Administration: Ip; three times a week for 2.5 weeks Experimental Results: Suppressed a lung metastasis in the Balb/c Xenograft model. In vivo animal studies with EW-7195 typically involve administration of the compound to rodent models of cancer, fibrosis, or other TGF-β-driven diseases. In breast cancer metastasis models, EW-7195 suppresses EMT and inhibits metastatic spread to the lung. In diabetic nephropathy models, EW-7195 attenuates disease progression through suppression of fibrogenesis and inflammation. Endpoints include assessment of tumor growth and metastasis, measurement of fibrotic markers, evaluation of inflammatory markers, and pharmacokinetic profiling. All procedures must comply with institutional animal care and use guidelines. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for EW-7195 are not extensively documented in the publicly available literature. The compound has a molecular weight of 430.46 g/mol and a molecular formula of C₂₃H₂₂N₆O₃. As a small molecule with favorable physicochemical properties, it may have suitable characteristics for oral bioavailability, though detailed PK parameters have not been published. The compound is typically stored under conditions recommended for research chemicals. Further studies are needed to characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
EW-7195 is intended for research use only and is not approved for human therapeutic applications. As a research chemical, comprehensive toxicological data are not extensively documented in the publicly accessible literature. Standard safety precautions should be observed when handling this compound, including the use of appropriate personal protective equipment. As with all research chemicals, comprehensive toxicological profiling would be required before any consideration for clinical development. The compound should be handled in well-ventilated areas with proper waste disposal procedures.
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| References | |
| Additional Infomation |
EW-7195 (CAS#: 1352609-28-9) is a potent and highly selective small molecule inhibitor of ALK5 (TβRI) with an IC₅₀ of 4.83 nM. It functions by blocking the ATP-binding site of ALK5, preventing phosphorylation of SMAD2 and SMAD3. EW-7195 inhibits TGF-β1-induced Smad signaling, suppresses EMT, and inhibits breast cancer metastasis to the lung. It also attenuates diabetic nephropathy progression. This compound is not a drug and has not undergone clinical trials.
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| Molecular Formula |
C23H18N8
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|---|---|
| Molecular Weight |
406.442622661591
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| Exact Mass |
406.165
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| CAS # |
1352609-28-9
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| PubChem CID |
54767248
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
649
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C(CNC2C=CC=C(C#N)C=2)=NC(C2C=CC3=NC=NN3C=2)=C1C1C=CC=C(C)N=1
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| InChi Key |
KEADGKSQIBFYEE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H18N8/c1-15-4-2-7-19(28-15)23-22(17-8-9-21-26-14-27-31(21)13-17)29-20(30-23)12-25-18-6-3-5-16(10-18)11-24/h2-10,13-14,25H,12H2,1H3,(H,29,30)
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| Chemical Name |
3-[[5-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-imidazol-2-yl]methylamino]benzonitrile
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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: 50 mg/mL (123.02 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 | 2.4604 mL | 12.3019 mL | 24.6039 mL | |
| 5 mM | 0.4921 mL | 2.4604 mL | 4.9208 mL | |
| 10 mM | 0.2460 mL | 1.2302 mL | 2.4604 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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