| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 5.8 nM (BTK), 49.0 nM (BMX), 440 nM (ITK), 190 nM (TXK), 220 nM (TEC), 2.60 μM (BLK)[1]
BTK (Bruton's tyrosine kinase). JS25 inactivates BTK through covalent binding, specifically by chelating the ATP-binding pocket residue Tyr551. |
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| ln Vitro |
JS25 (0-50 μM; 72 h) prevents myeloid and lymphoid B-cell cancer cell lines from proliferating. With IC50s of 28.5 nM, 49.0 nM, 0.44 μM, 0.19 μM, 0.22 μM, and 2.60 μM, respectively, JS25 demonstrates its inhibitory effectiveness against BTK, BMX, ITK, TXK, TEC, and BLK; however, it exhibits minimal inhibition against additional BTK pathway-related proteins (EGFR, ERBB2, and JAK3). Comparing JS25 to Ibrutinib and Acalabrutinib, the selectivity profile of JS25 is preferable[1]. BTK is degraded by JS25 (10 μM; 0, 4, 15 h), which also prevents BTK from being expressed in tumor cells and from having catalytic activity[1]. In primary diffuse large B-cell lymphoma (DLBCL) samples, JS25 (10 μM; 72 h) causes selective ex vivo cytotoxicity and suppresses the growth of Burkitt's lymphoma tumors[1].
JS25 inhibits BTK with an IC50 of 5.8 nM. In cell culture, JS25 (10 uM; 72 h) inhibits the proliferation of Burkitt's lymphoma cells and induces selective ex vivo cytotoxicity in primary diffuse large B-cell lymphoma (DLBCL) samples. It effectively blocks B-cell receptor signaling and downstream pathways. |
| ln Vivo |
In a mouse xenograft model of Burkitt's lymphoma, JS25 (10 mg/kg and 20 mg/kg; ip; every 2 days, for 14 d) suppresses tumor growth and significantly reduces the creation of secondary tumors[1]. JS25 (1, 2.5, and 5 μM; injection; once daily for two days) is more effective than isbrutinib at reducing tumor burden in xenografts of chronic lymphocytic leukemia generated from zebrafish patients[1].
In a murine xenograft model of Burkitt's lymphoma, JS25 demonstrates significant anti-tumor efficacy, promoting tumor regression and improving overall outcomes. The compound exhibits excellent brain penetration, suggesting potential utility for treating CNS lymphoma. It has also shown effects in models of autoimmunity. |
| Enzyme Assay |
Cell-free BTK activity assays are performed using recombinant human BTK enzyme. The enzyme is incubated with a peptide substrate and ATP in the presence of increasing concentrations of JS25 (0.01-1000 nM) in reaction buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 2 mM DTT). After 30-60 min at 30degC, the reaction is quenched, and IC50 is calculated by quantifying phosphorylated substrate using a luminescence-based kinase assay (e.g., ADP-Glo).
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| Cell Assay |
Human B-cell lymphoma cell lines (e.g., Ramos, SU-DHL-4) are seeded in 96-well plates and treated with JS25 at various concentrations (0.1-10 uM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. Apoptosis is measured by Annexin V/PI staining followed by flow cytometry. BTK phosphorylation at Tyr223 (autophosphorylation) and downstream signaling proteins (PLCgamma2, ERK, AKT) are analyzed by Western blot.
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| Animal Protocol |
Animal/Disease Models: Female adult BALB/c/NSG mice with Raji cells (sc)[1]
Doses: 10 mg/kg and 20 mg/kg Route of Administration: intraperitoneal (ip) injection; every 2 days for 14 days Experimental Results: Caused a 30-40% reduction of the subcutaneous (sc) tumor and an overall reduction in the percentage of metastasis and secondary tumor formation. For in vivo efficacy studies, female NOD/SCID or BALB/c nude mice are subcutaneously inoculated with Burkitt's lymphoma cells (e.g., Ramos). When tumors reach approximately 100-200 mm3, JS25 is administered orally or intraperitoneally at doses of 10-50 mg/kg daily for 2-4 weeks. Tumor volumes are measured with calipers every 2-3 days. Body weight is monitored as a toxicity indicator. At study termination, tumors are excised for analysis of BTK target engagement and downstream signaling. JS25 crosses the BBB, enabling CNS lymphoma studies. |
| ADME/Pharmacokinetics |
JS25 (MW 524.59, C29H24N4O4S) is orally bioavailable and brain-penetrant. PK parameters have not been fully published; however, the compound exhibits moderate clearance and half-life in preclinical species. It is soluble in DMSO (100 mg/mL) and can be formulated for in vivo administration using 5% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline. For in vitro studies, JS25 is stable in DMSO at -20degC.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for JS25. In published in vivo studies at doses up to 50 mg/kg, no overt signs of toxicity (weight loss, behavioral changes, or mortality) were observed. The compound is a covalent BTK inhibitor, a class known to have favorable safety profiles in the clinic. However, comprehensive toxicological assessments have not been published. No clinical trials have been conducted.
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| References | |
| Additional Infomation |
JS25 (CAS 2411771-95-2) is a research-grade compound, not FDA-approved. It is a selective, covalent BTK inhibitor that inactivates BTK by chelating Tyr551 with an IC50 of 5.8 nM. The compound is available from commercial suppliers for research use only, with purity ≥98%. It is useful for studying B-cell receptor signaling and has potential applications in B-cell malignancies and autoimmune disorders. Synonyms: JS-25.
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| Molecular Formula |
C29H24N4O4S
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|---|---|
| Molecular Weight |
524.590265274048
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| Exact Mass |
524.151
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| CAS # |
2411771-95-2
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| PubChem CID |
155368276
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| Appearance |
Light yellow to light brown solid powder
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| LogP |
4.1
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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 |
6
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| Heavy Atom Count |
38
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| Complexity |
1030
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC1=CC(N2C3=C(C=NC4=CC(C5=CC=C(NS(C)(=O)=O)C=C5)=CC=C43)C=CC2=O)=CC(C)=C1)(=O)C=C
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| InChi Key |
WPVJPKXENBARHX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H24N4O4S/c1-4-27(34)31-23-13-18(2)14-24(16-23)33-28(35)12-8-21-17-30-26-15-20(7-11-25(26)29(21)33)19-5-9-22(10-6-19)32-38(3,36)37/h4-17,32H,1H2,2-3H3,(H,31,34)
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| Chemical Name |
N-[3-[8-[4-(methanesulfonamido)phenyl]-2-oxobenzo[h][1,6]naphthyridin-1-yl]-5-methylphenyl]prop-2-enamide
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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: Please store this product in a sealed and protected environment, 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) |
DMSO: 20 mg/mL (38.13 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 | 1.9063 mL | 9.5313 mL | 19.0625 mL | |
| 5 mM | 0.3813 mL | 1.9063 mL | 3.8125 mL | |
| 10 mM | 0.1906 mL | 0.9531 mL | 1.9063 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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