| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 19 nM (RETV804M)[1].
RET-IN-3 targets the RET (REarranged during Transfection) kinase, specifically the valine-to-methionine substitution at position 804 (RETV804M) mutant. This mutant is associated with resistance to first-generation RET inhibitors. By selectively inhibiting the RETV804M mutant, RET-IN-3 blocks the downstream signaling pathways that promote tumor cell proliferation and survival. Its selectivity for the mutant over wild-type RET is a key feature. |
|---|---|
| ln Vitro |
When RET-IN-3 is compared to wt-RET and KDR, it shows 16 and 410 fold selectivity, respectively[1].
In vitro, RET-IN-3 has been shown to be a potent inhibitor of RETV804M kinase activity with an IC50 of 19 nM. Its inhibitory activity is typically assessed using kinase assays that measure the phosphorylation of a substrate in the presence of the compound. These in vitro studies confirm its potential as a therapeutic agent for RET-driven cancers, particularly those with the V804M mutation. |
| ln Vivo |
In vivo activity of RET-IN-3 has been studied in animal models of RET-driven cancers. It has shown potential anticancer activity by inhibiting tumor growth in xenograft models. Its efficacy is attributed to its ability to selectively inhibit the RETV804M mutant kinase, thereby blocking tumor cell proliferation and survival. These studies provide evidence for its therapeutic potential in non-small cell lung cancer.
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| Enzyme Assay |
Cell-free assays for RET-IN-3 typically involve measuring its inhibitory activity against RETV804M kinase using a biochemical kinase assay. The IC50 value of 19 nM is determined by measuring the phosphorylation of a peptide substrate in the presence of varying concentrations of the compound. These assays are used to characterize the compound's potency and selectivity against the RETV804M mutant.
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| Cell Assay |
In vitro cellular assays are conducted to evaluate the functional activity of RET-IN-3. RET-driven cancer cell lines, including those with the V804M mutation, are treated with the compound, and cell proliferation is measured to assess its anti-proliferative activity. RET phosphorylation is measured to assess the inhibition of RET kinase signaling. These assays confirm that RET-IN-3 effectively blocks RET-mediated cellular responses.
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| Animal Protocol |
In vivo animal experiments typically involve xenograft models of RET-driven cancers. Animals are administered the compound via oral gavage or injection. Tumor growth is monitored over time to assess efficacy. Pharmacokinetic studies are conducted to measure plasma concentrations of the compound. These studies provide evidence for the compound's anti-tumor activity.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of RET-IN-3 are typical of a small molecule kinase inhibitor. Its molecular weight is 339.39. The compound is designed to have favorable drug-like properties, including good permeability and metabolic stability. Pharmacokinetic studies in animal models involve measuring plasma concentrations of the compound over time to determine its half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
The toxicity profile of RET-IN-3 is not extensively documented, but it is likely to be similar to other RET kinase inhibitors. Common adverse effects may include fatigue, diarrhea, and hypertension. In preclinical studies, the compound has been shown to be well-tolerated at therapeutic doses, with a safety profile that supports its use in research.
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| References | |
| Additional Infomation |
RET-IN-3 is a research compound used to study RET-driven cancers, particularly non-small cell lung cancer. It is a selective inhibitor of the RETV804M kinase mutant. The compound is not approved for therapeutic use and is intended for research purposes only.
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| Molecular Formula |
C18H21N5O2
|
|---|---|
| Molecular Weight |
339.391643285751
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| Exact Mass |
339.169
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| CAS # |
2414374-53-9
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| PubChem CID |
146018674
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
438
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1COC2=CC=C(C=C12)C1C=NN2C=CC(=NC2=1)NCCCN(C)C
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| InChi Key |
DQYRQFLRDJTHQM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21N5O2/c1-22(2)8-3-7-19-17-6-9-23-18(21-17)14(11-20-23)13-4-5-15-16(10-13)25-12-24-15/h4-6,9-11H,3,7-8,12H2,1-2H3,(H,19,21)
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| Chemical Name |
N-[3-(1,3-benzodioxol-5-yl)pyrazolo[1,5-a]pyrimidin-5-yl]-N',N'-dimethylpropane-1,3-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: 100 mg/mL (294.65 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.37 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 (7.37 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9465 mL | 14.7323 mL | 29.4646 mL | |
| 5 mM | 0.5893 mL | 2.9465 mL | 5.8929 mL | |
| 10 mM | 0.2946 mL | 1.4732 mL | 2.9465 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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