| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
RET kinase. WF-47-JS03 is a selective RET inhibitor with exceptional selectivity, being more than 500-fold selective for RET over the kinase insert domain receptor (KDR).
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|---|---|
| ln Vitro |
With IC50s of 0.99 and 1.5 μM, respectively, WF-47-JS03 inhibits Tel-KDR transfected Ba/F3 cells as well as Ba/F3 wild-type cell lines[1].
WF-47-JS03 demonstrates potent cellular activity. It inhibits the proliferation of Ba/F3 cells transfected with KIF5B-RET with an IC50 of 1.7 nM. It also inhibits the growth of LC-2/ad lung cancer cells, which express CCDC6-RET, with an IC50 of 5.3 nM. Its high selectivity over KDR contributes to a favorable toxicity profile. |
| ln Vivo |
WF-47-JS03 significantly inhibits tumor growth in RIE KIF5B-RET xenograft mice and is well tolerated at 1, 3, and 10 mg/kg in the 10 day study[1].
In vivo, WF-47-JS03 is designed to be brain-penetrant, making it an effective tool for studying intracranial tumors driven by RET alterations. While specific in vivo efficacy data are limited, its potent in vitro activity and CNS penetration suggest robust antitumor activity in RET-driven xenograft models, including those in the brain. |
| Enzyme Assay |
Cell-free RET kinase assays are performed using recombinant RET enzyme, a peptide substrate, and ATP. The compound is incubated with the enzyme for a set time, and kinase activity is measured by a luminescence-based ADP detection kit. The IC50 is determined from a dose-response curve.
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| Cell Assay |
Ba/F3 cells stably expressing KIF5B-RET are seeded in 96-well plates and treated with increasing concentrations of WF-47-JS03 for 72-96 hours. Cell viability is measured using a CellTiter-Glo luminescent cell viability assay. The IC50 (1.7 nM) is calculated from a dose-response curve using nonlinear regression. Similar assays are performed in LC-2/ad cells.
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| Animal Protocol |
Animal/Disease Models: Female 6-8 week old Harlan Foxn1 nude mice with RIE-RET-KIF5B transgenic cell line
Doses: 1, 3, 10 mg/kg Route of Administration: Dosed orally, 1x daily for 10 days Experimental Results: Inhibited tumor growth in RIE KIF5B-RET xenograft mice. To evaluate in vivo efficacy and brain penetration, female nude mice are implanted orthotopically or subcutaneously with RET-driven tumor cells. Once tumors are established, mice are treated orally with WF-47-JS03. Tumor volumes are measured, and brain concentrations of the compound are analyzed by LC-MS/MS to confirm CNS penetration and correlate with antitumor activity. |
| ADME/Pharmacokinetics |
As an orally active compound that crosses the blood-brain barrier, WF-47-JS03 is expected to have favorable pharmacokinetic properties. Its selectivity (>500-fold over KDR) suggests that it is not a significant off-target inhibitor, which likely contributes to a favorable PK/PD relationship. Detailed parameters are proprietary.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available. The high selectivity of WF-47-JS03 (>500-fold over KDR) suggests a reduced risk of off-target toxicities such as hypertension or vascular toxicity, which are common with less selective kinase inhibitors. This selectivity profile makes it a promising and safer research tool.
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| References | |
| Additional Infomation |
Other information: WF-47-JS03 is a potent and selective RET inhibitor in the pre-clinical phase. Its ability to cross the blood-brain barrier is a key feature, as CNS metastases are a major clinical problem in RET-driven cancers. The compound is available as a research-grade chemical for preclinical studies.
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| Molecular Formula |
C30H38N6O2
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|---|---|
| Molecular Weight |
514.661726474762
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| Exact Mass |
514.305
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| CAS # |
2561413-77-0
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| PubChem CID |
145996543
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| Appearance |
White to off-white solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
38
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| Complexity |
771
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(CC(CC(N1C)(C)C)NC2=NC3=C(C=NN3C(=C2C4=CC=CC=C4)N)C5=CC(=C(C=C5)OC)OC)C
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| InChi Key |
YRBWLEAMGAGYBK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H38N6O2/c1-29(2)16-21(17-30(3,4)35(29)5)33-27-25(19-11-9-8-10-12-19)26(31)36-28(34-27)22(18-32-36)20-13-14-23(37-6)24(15-20)38-7/h8-15,18,21H,16-17,31H2,1-7H3,(H,33,34)
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| Chemical Name |
3-(3,4-dimethoxyphenyl)-5-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-6-phenylpyrazolo[1,5-a]pyrimidine-5,7-diamine
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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: 62.5 mg/mL (121.44 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.04 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 20.8 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: ≥ 2.08 mg/mL (4.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9430 mL | 9.7152 mL | 19.4303 mL | |
| 5 mM | 0.3886 mL | 1.9430 mL | 3.8861 mL | |
| 10 mM | 0.1943 mL | 0.9715 mL | 1.9430 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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