Vepafestinib
Based on 1 Customer Validation
Vepafestinib (TAS0953/HM06) is a next-generation brain-penetrant, selective and orally active RET inhibitor with an IC50 value of 0.33 nM. Vepafestinib inhibits the phosphorylation of RET and its downstream signaling pathways, thus blocking the growth and signal transduction of tumor cells and inducing cell cycle arrest and apoptosis. Vepafestinib can be used in the research of various RET-driven cancers, such as non-small cell lung cancer, thyroid cancer and other disease areas.
For research use only. We do not sell to patients.
- Purity: 98.61%
- CAS No.: 2129515-96-2
- Formula: C26H30N6O3
- Molecular Weight:474.55
-
Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
-
Apoptosis Compound Library
HY-L003
-
Kinase Inhibitor Library
HY-L009
-
Protein Tyrosine Kinase Compound Library
HY-L016
-
Anti-Cancer Compound Library
HY-L025
-
Clinical Compound Library
HY-L026
-
CNS-Penetrant Compound Library
HY-L028
-
Drug Repurposing Compound Library
HY-L035
-
Endocrinology Compound Library
HY-L047
-
Orally Active Compound Library
HY-L061
-
Anti-Lung Cancer Compound Library
HY-L075
-
Anti-Liver Cancer Compound Library
HY-L101
-
Heterocyclic Compound Library
HY-L138
-
Membrane Protein-targeted Compound Library
HY-L149
-
Membrane Receptor-targeted Compound Library
HY-L150
-
Highly Selective Inhibitors Library
HY-L158
-
Highly Selective Activators Library
HY-L159
-
Cell Death Library
HY-L162
-
Bioactive Compound Library Max
HY-L181
-
MCE Bioactive Compound Library
HY-L001V
-
Drug Repurposing Compound Library Plus
HY-L035P
-
Clinical Compound Library Plus
HY-L026P
-
Bioactive Compound Library
HY-L001
-
Anti-Brain Cancer Compound Library
HY-L188
-
Protein Kinase Compound Library
HY-L196
-
Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
-
High-Throughput Bioactive Compound Library
HY-L205
-
Posttranslational Modification Library
HY-L226
-
Alkyne Compound Library
HY-L258
Biological Activity
Vepafestinib (0.01-10000 nM; 96 h) inhibits growth of all tumor cell lines[1].
Vepafestinib (5-500 nM; 2 h) inhibits cell growth and blocks the phosphorylation of RET and ERK in Ba/F3 cells expressing KIF5B-RET or its mutants[1].
Vepafestinib (100 nM; 6-24 h) inhibits the phosphorylation of RET, AKT, S6, ERK1 and ERK2 in LUAD-0002AS1 cells. And ownregulates the cell cycle regulator cyclin D1, induces the expression of apoptosis markers.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:LUAD-0002AS1, TT, ECLC5B cells
-
Concentration:0.01 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1000 nM, 10000 nM
-
Incubation Time:96 h
-
Result:Inhibited growth of all tumor cell lines.
-
Cell Line:Ba/F3 cells expressing KIF5B-RET or mutants
-
Concentration:5 nM, 50 nM and 500 nM
-
Incubation Time:2 h
-
Result:Inhibited the growth of Ba/F3 cells expressing KIF5B-RET or mutants.
Blocked the phosphorylation of RET and ERK, with near-complete inhibition of phosphorylation of RETG810R, RETG810S and RETG810C at 100 nM.
-
Cell Line:LUAD-0002AS1 cells
-
Concentration:100 nM
-
Incubation Time:24 h
-
Result:Downregulated the cell cycle regulator cyclin D1, increased the expression of the cell cycle inhibitor p27, and downregulated p21.
Induced the expression of apoptosis markers such as cleaved PARP (c-PARP), BIM and PUMA.
Vepafestinib (10-50 mg/kg; oral administration; twice daily; continuous administration) effectively inhibits tumor growth without affecting animal body weight in mouse models of Ba/F3 KIF5B-RETWT or Ba/F3 KIF5B-RETG810R allograft tumors[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Female athymic nude mice (6-8 weeks old), implanted subcutaneously with NIH-3T3 cells expressing CCDC6-RET fusion complementary DNA[1].
-
Dosage:12.5 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg
-
Administration:Oral gavage, once or twice daily, for 7 days
-
Result:Resulted in a dose-dependent decrease in the growth of NIH-3T3-RET xenograft tumors. All dosages tested significantly reduced tumor volume, and there was no statistically significant reduction in animal weight.
-
Animal Model:Female NOD-SCID gamma (NSG) mice (6-8 weeks old), implanted subcutaneously with ECLC5B xenograft tumors[1]
-
Dosage:25 mg/kg, 50 mg/kg, 100 mg/kg
-
Administration:Oral gavage, once or twice daily, for 35 days
-
Result:Significantly reduced ECLC5B xenograft tumor growth, and there was no significant reduction in animal weight.
-
Animal Model:Female NSG mice (6-8 weeks old), implanted subcutaneously with LUAD-0057AS1 patient-derived xenograft (PDX) tumors[1]
-
Dosage:50 mg/kg, 100 mg/kg
-
Administration:Oral gavage, once or twice daily, for 21 days
-
Result:Significantly reduced the volume of LUAD-0057AS1 PDX tumors, and there was no significant reduction in animal weight.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
-
CAS No. 2129515-96-2
-
Appearance Solid
-
Molecular Weight 474.55
-
Formula C26H30N6O3
-
Color Light yellow to yellow
-
SMILES
O=C(C1=C(C#CCN2CCOCC2)N(C3(C)CC3)C4=NC=NC(N)=C41)NC5=CC=C(COC)C=C5
-
Synonyms
TAS0953/HM06
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 50 mg/mL (105.36 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1 mg/mL (2.11 mM); Clear solution
This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
-
Data Sheet (283 KB)
-
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
-
Handling Instructions (2659 KB)
References
[1]. Miyazaki I, et al. Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations. Nat Cancer. 2023 Sep;4(9):1345-1361. doi: 10.1038/s43018-023-00630-y. Epub 2023 Sep 21. Erratum in: Nat Cancer. 2023 Oct;4(10):1526. [Content Brief]
[2]. Vepafestinib: a RET-selective inhibitor with enhanced CNS penetrance targets therapy-resistant mutants. Nat Cancer. 2023 Sep;4(9):1220-1221. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1073 mL | 10.5363 mL | 21.0726 mL | 52.6815 mL |
| 5 mM | 0.4215 mL | 2.1073 mL | 4.2145 mL | 10.5363 mL | |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1073 mL | 5.2681 mL | |
| 15 mM | 0.1405 mL | 0.7024 mL | 1.4048 mL | 3.5121 mL | |
| 20 mM | 0.1054 mL | 0.5268 mL | 1.0536 mL | 2.6341 mL | |
| 25 mM | 0.0843 mL | 0.4215 mL | 0.8429 mL | 2.1073 mL | |
| 30 mM | 0.0702 mL | 0.3512 mL | 0.7024 mL | 1.7560 mL | |
| 40 mM | 0.0527 mL | 0.2634 mL | 0.5268 mL | 1.3170 mL | |
| 50 mM | 0.0421 mL | 0.2107 mL | 0.4215 mL | 1.0536 mL | |
| 60 mM | 0.0351 mL | 0.1756 mL | 0.3512 mL | 0.8780 mL | |
| 80 mM | 0.0263 mL | 0.1317 mL | 0.2634 mL | 0.6585 mL | |
| 100 mM | 0.0211 mL | 0.1054 mL | 0.2107 mL | 0.5268 mL |
Vepafestinib Related Classifications
HY-132846 Related Classifications
Powered by Bioz