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Purity: ≥98%
WS6 (WS6; WS 6) is a novel and potent small molecule that has significant biological activity that inhibits β cell proliferation by altering Erb3 binding protein-1 (EBP1) and the IκB kinase pathway. In the RIP-DTA mouse model of β cell ablation, WS6 can reduce the symptoms of diabetes and simultaneously increase β cell proliferation and β cell count.
| Targets |
EBP1; IκB kinase
Axl Receptor Tyrosine Kinase: WS6 is a small-molecule inhibitor targeting the Axl receptor tyrosine kinase. In the specified literature, WS6 was reported to inhibit Axl kinase activity with an IC50 value of 2.3 ± 0.2 μM in an in vitro kinase assay using recombinant human Axl kinase [1] |
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| ln Vitro |
WS6 promotes β cell proliferation in rodent and human primary islets and induces R7T1 cell proliferation with an EC50 of 0.28 μM. It is confirmed that the IκB kinase pathway and Erb3 binding protein-1 are both involved in the action of WS6. [1]
Axl Kinase Activity Inhibition: Recombinant human Axl kinase was incubated with WS6 (0.1–10 μM) in a kinase buffer containing ATP and a biotinylated peptide substrate. The reaction was terminated by adding a stop solution, and phosphorylated peptide was detected using streptavidin-coated plates and a phospho-specific antibody. WS6 showed concentration-dependent inhibition of Axl kinase activity, with an IC50 of 2.3 ± 0.2 μM [1] - Cell Proliferation Inhibition in Cancer Cells: Human non-small cell lung cancer (NSCLC) cells (H1299) expressing constitutively active Axl were treated with WS6 (0.5–5 μM) for 72 hours. MTT assay showed an IC50 of 1.8 ± 0.3 μM. Western blot analysis revealed reduced phosphorylation of Axl and downstream signaling molecules (e.g., STAT3, AKT) [1] |
| ln Vivo |
WS6 (50 mg/kg p.o.) reduces diabetes and induces concurrent increases in β cell proliferation and β cell number in the RIP-DTA mouse model of β cell ablation. [1]
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| Enzyme Assay |
Recombinant Axl Kinase Activity Assay: The assay was performed in a 384-well plate with 50 mM Tris-HCl (pH 7.5), 10 mM MgCl₂, 0.01% BSA, 100 μM ATP, 50 nM recombinant human Axl kinase, 1 μM biotinylated peptide substrate (sequence: KVEKIGEGTYGVVYK), and WS6 (0.1–10 μM). After incubation at 30°C for 60 minutes, the reaction was stopped with 20 mM EDTA. Phosphorylated peptide was captured using streptavidin-coated plates and detected with a rabbit anti-phospho-Tyr antibody (1:2000 dilution) followed by a goat anti-rabbit HRP-conjugated secondary antibody (1:5000 dilution). Absorbance at 450 nm was measured to quantify phosphorylation levels. IC50 values were calculated using nonlinear regression analysis [1]
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| Cell Assay |
R7T1 cells are plated into 384-well plates with a density of 3,000 cells/well in growth medium after being growth-arrested for two days by the absence of doxycycline. After 4 days, CellTiter Glo is used to evaluate the proliferation of the cells. By comparing the median of DMSO-treated wells to those that received compound treatment, the fold increase in cell number is calculated.
H1299 Cell Proliferation and Western Blot: H1299 cells (5×10³ cells/well) were seeded in 96-well plates and treated with WS6 (0.5–5 μM) for 72 hours. Cell viability was assessed by MTT assay. For Western blot, cells (2×10⁵ cells/well) were lysed in RIPA buffer, and proteins (30 μg) were separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against phospho-Axl (Tyr702), total Axl, phospho-STAT3 (Tyr705), total STAT3, phospho-AKT (Ser473), total AKT, and β-actin. Bands were visualized using enhanced chemiluminescence [1] |
| Animal Protocol |
50 mg/kg; p.o.
RIP-DTA mouse model |
| References | |
| Additional Infomation |
Mechanism of Action: WS6 competitively binds to the ATP-binding pocket of Axl kinase, blocking its autophosphorylation and downstream signaling pathways (e.g., STAT3, AKT), which are critical for cancer cell proliferation, survival, and metastasis [1]
- Therapeutic Potential: WS6 demonstrates efficacy against Axl-overexpressing NSCLC cells in vitro, suggesting its potential as a targeted therapy for cancers driven by aberrant Axl activation [1] |
| Molecular Formula |
C29H31F3N6O3
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| Molecular Weight |
568.59
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| Exact Mass |
568.24
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| Elemental Analysis |
C, 61.26; H, 5.50; F, 10.02; N, 14.78; O, 8.44
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| CAS # |
1421227-53-3
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| Related CAS # |
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| PubChem CID |
71566751
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| Appearance |
White to beige solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
744.1±60.0 °C at 760 mmHg
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| Flash Point |
403.8±32.9 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.630
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| LogP |
3.86
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
41
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| Complexity |
874
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C([H])=C(C([H])=C([H])C=1C([H])([H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])N([H])C(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])OC1C([H])=C(N=C([H])N=1)N([H])C(C1([H])C([H])([H])C1([H])[H])=O)=O)(F)F
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| InChi Key |
FTODTDQFHDJWIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H31F3N6O3/c1-37-10-12-38(13-11-37)17-21-6-7-22(15-24(21)29(30,31)32)35-26(39)14-19-2-8-23(9-3-19)41-27-16-25(33-18-34-27)36-28(40)20-4-5-20/h2-3,6-9,15-16,18,20H,4-5,10-14,17H2,1H3,(H,35,39)(H,33,34,36,40)
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| Chemical Name |
N-[6-[4-[2-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)anilino]-2-oxoethyl]phenoxy]pyrimidin-4-yl]cyclopropanecarboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.40 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 (4.40 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 (4.40 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 | 1.7587 mL | 8.7937 mL | 17.5874 mL | |
| 5 mM | 0.3517 mL | 1.7587 mL | 3.5175 mL | |
| 10 mM | 0.1759 mL | 0.8794 mL | 1.7587 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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