| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Entrectinib-d4 targets TrkA/B/C (tropomyosin receptor kinases), ROS1, and ALK (anaplastic lymphoma kinase). The parent compound Entrectinib is an orally active, blood-brain-penetrating, centrally active inhibitor with IC50 values of 1 nM for TrkA, 3 nM for TrkB, 5 nM for TrkC, 12 nM for ROS1, and 7 nM for ALK. By inhibiting these kinases, Entrectinib blocks cancer cell proliferation and survival signaling pathways.
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| ln Vitro |
In vitro studies demonstrate that Entrectinib-d4 is the deuterated form of Entrectinib, which is a potent inhibitor of TrkA/B/C, ROS1, and ALK with IC50 values of 1, 3, 5, 12, and 7 nM, respectively. Entrectinib induces apoptosis and cell cycle arrest in cancer cells. The compound has antitumor activity in various cancer cell lines. Detailed in vitro activity data for the deuterated form are expected to be similar to the parent compound.
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| ln Vivo |
In vivo activity of Entrectinib-d4 is inferred from the parent compound Entrectinib, which has antitumor activity and can reduce bleomycin-induced pulmonary fibrosis in mice. Entrectinib is orally active and blood-brain-penetrating, making it suitable for central nervous system applications. The deuterated form is used for pharmacokinetic and metabolic studies. Detailed in vivo data for the deuterated form are not extensively documented.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for Entrectinib-d4 involves measuring its inhibitory activity against TrkA/B/C, ROS1, and ALK kinases. Kinase assays using purified recombinant kinases incubated with the compound at varying concentrations, along with ATP and peptide substrates, are performed. Kinase activity is measured by quantifying phosphorylation levels. IC50 values are determined from dose-response curves. Standard protocols include appropriate positive controls and vehicle controls.
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| Cell Assay |
In vitro cell-based assays for Entrectinib-d4 are conducted using cancer cell lines expressing Trk, ROS1, or ALK fusions or mutations. Cells are treated with the compound at various concentrations, and cell viability is measured using MTT or CCK-8 assays. Apoptosis is assessed by measuring caspase activation or Annexin V staining. Cell cycle arrest is evaluated by flow cytometry. Standard protocols include appropriate positive controls and vehicle controls.
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| Animal Protocol |
In vivo animal studies for Entrectinib-d4 would typically be conducted using xenograft mouse models of cancers harboring Trk, ROS1, or ALK alterations. Animals would be administered the compound orally, and tumor growth inhibition would be monitored. The compound's ability to reduce bleomycin-induced pulmonary fibrosis in mice has been demonstrated for the parent compound. Pharmacokinetic parameters would be determined from plasma samples.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Entrectinib-d4 are expected to be similar to the parent compound Entrectinib, which is orally active and blood-brain-penetrating. The deuterated form is used as a stable isotope-labeled compound for research applications, including pharmacokinetic and metabolic studies. Detailed pharmacokinetic parameters for the deuterated form are not extensively documented in the available literature. The compound is intended for research use only.
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| Toxicity/Toxicokinetics |
Toxicity information for Entrectinib-d4 is expected to be similar to the parent compound Entrectinib. Standard safety precautions for handling research chemicals should be followed. The compound is designated for research use only and is not for human therapeutic applications. No detailed toxicity data are available from the search results.
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| References |
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| Additional Infomation |
Entrectinib-d4 (NMS-E628-d4; RXDX-101-d4) is the deuterated form of Entrectinib, an orally active, BBB-penetrating inhibitor of TrkA/B/C (IC50 1, 3, 5 nM), ROS1 (12 nM), and ALK (7 nM). Entrectinib induces apoptosis and cell cycle arrest and has antitumor activity. It is intended for research use only.
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| Molecular Formula |
C31H30D4F2N6O2
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| Molecular Weight |
564.66
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| Appearance |
Typically exists as solid at room temperature
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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) |
Typically soluble in DMSO (e.g. 10 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7710 mL | 8.8549 mL | 17.7098 mL | |
| 5 mM | 0.3542 mL | 1.7710 mL | 3.5420 mL | |
| 10 mM | 0.1771 mL | 0.8855 mL | 1.7710 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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