| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
RET kinase (wild-type, G810 solvent-front mutants, V804 gatekeeper mutants). Vepafestinib is a highly selective RET inhibitor, with a unique binding mode that allows it to overcome common resistance mutations.
|
|---|---|
| ln Vitro |
Vepafestinib potently inhibits RET wild-type and mutants, including G810R/S/C and V804L/M. In a panel of 255 kinases, it is remarkably selective, with only RET inhibited by >50% at a concentration 70-fold higher than its IC50. It potently suppresses RET-driven cell proliferation with low nanomolar GI50 values.
|
| ln Vivo |
In mouse xenograft models of KIF5B-RET-driven tumors, vepafestinib induces profound and dose-dependent tumor regression, including models harboring the G810R resistance mutation. Its high brain penetration suggests strong potential for treating CNS metastases. It has shown better efficacy than vandetanib and comparable efficacy to selpercatinib and pralsetinib.
|
| Enzyme Assay |
Cell-free RET kinase assays are performed using recombinant RET enzymes (wild-type or mutants). The compound is incubated with the enzyme and a peptide substrate in the presence of ATP for 30-60 minutes. Activity is measured by a luminescence-based ADP detection kit. Selectivity is assessed using a commercial kinase panel of 255 kinases at 23 nM (approx. 70x IC50).
|
| Cell Assay |
Ba/F3 cells expressing various KIF5B-RET fusion constructs (wild-type, G810R, G810S, V804L) are seeded in 96-well plates. Cells are treated with a range of vepafestinib concentrations for 72-96 hours. Cell proliferation is measured using an MTT or CellTiter-Glo assay, and the 50% growth inhibition (GI50) is calculated.
|
| Animal Protocol |
Female BALB/c nude mice are subcutaneously injected with Ba/F3 cells expressing KIF5B-RET fusions. After tumors reach a predetermined size, mice are randomized and treated orally with vepafestinib at various doses. Tumor volumes are measured with calipers twice weekly. For pharmacodynamic analysis, tumors are collected for immunoblotting to assess RET and downstream signaling.
|
| ADME/Pharmacokinetics |
Vepafestinib is an orally bioavailable compound with favorable physicochemical properties that enable high brain penetration. Its brain-to-plasma ratio is expected to be high, supporting its use against brain metastases. Detailed parameters such as half-life, Cmax, and oral bioavailability in preclinical species are reported in research articles.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are publicly detailed. As a selective RET inhibitor, its safety profile is expected to be manageable. Preclinical toxicology studies have likely been conducted to support clinical trials, showing a tolerable profile with no unexpected off-target toxicities. Clinical trials (Phase 1/2) are ongoing to evaluate its safety in humans.
|
| References | |
| Additional Infomation |
Vepafestinib is a highly bioavailable, selective inhibitor that inhibits wild-type, fusion, and mutant versions of the proto-oncogene receptor tyrosine kinase (RET), exhibiting potential antitumor activity. After oral administration, Vepafestinib selectively binds to and inhibits RET activity. This leads to the suppression of the growth of tumor cells with enhanced RET activity. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a crucial role in the development and progression of these cancers.
Other information: Vepafestinib is a pharmacologically advanced RET-selective inhibitor with best-in-class selectivity. Its unique binding mode, distinct from that of selpercatinib and pralsetinib, allows it to potently inhibit the RET G810R/S/C resistance mutations. It is a promising therapeutic for patients with RET-altered cancers who progress on first-line RET inhibitors. |
| Molecular Formula |
C26H30N6O3
|
|---|---|
| Molecular Weight |
474.5548
|
| Exact Mass |
474.237
|
| CAS # |
2129515-96-2
|
| PubChem CID |
134164132
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
1.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
35
|
| Complexity |
808
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C1C2=C(N([H])[H])N=C([H])N=C2N(C=1C#CC([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H])C1(C([H])([H])[H])C([H])([H])C1([H])[H])N([H])C1C([H])=C([H])C(C([H])([H])OC([H])([H])[H])=C([H])C=1[H]
|
| InChi Key |
SFXVRNLGOSAWIV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H30N6O3/c1-26(9-10-26)32-20(4-3-11-31-12-14-35-15-13-31)21(22-23(27)28-17-29-24(22)32)25(33)30-19-7-5-18(6-8-19)16-34-2/h5-8,17H,9-16H2,1-2H3,(H,30,33)(H2,27,28,29)
|
| Chemical Name |
4-amino-N-[4-(methoxymethyl)phenyl]-7-(1-methylcyclopropyl)-6-(3-morpholin-4-ylprop-1-ynyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 50 mg/mL (105.36 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1073 mL | 10.5363 mL | 21.0726 mL | |
| 5 mM | 0.4215 mL | 2.1073 mL | 4.2145 mL | |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1073 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04683250
Conditions:RET-altered Non Small Cell Lung Cancer|RET-altered Solid TumorsProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
