| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
AZD9291DA targets the epidermal growth factor receptor (EGFR), specifically the mutated forms such as L858R EGFR, Exon 19 deletion activating mutants, and the T790M resistance mutant. It inhibits both the activating and resistant EGFR mutations while sparing the normal form of EGFR found in skin and gut cells. This selectivity is a key feature of third-generation EGFR inhibitors, reducing the side effects seen with earlier therapies.
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| ln Vitro |
AZD9291DA is highly active in preclinical models, effectively inhibiting the kinase activity of mutant EGFR. Its des-acryl modification may alter its pharmacological properties compared to the parent compound, Osimertinib. The compound's activity against resistant EGFR mutations makes it a valuable tool for studying mechanisms of resistance in non-small cell lung cancer (NSCLC).
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| ln Vivo |
AZD9291 is well tolerated in animal models, suggesting that AZD9291DA, as an analogue, may exhibit similar in vivo characteristics. It has shown efficacy in preclinical models of NSCLC, particularly those harboring the T790M resistance mutation. The compound's selectivity for mutant over wild-type EGFR is expected to translate into a favorable in vivo safety profile.
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| Enzyme Assay |
The enzymatic activity of AZD9291DA can be assessed using kinase assays with recombinant EGFR proteins. The assay typically involves incubating the kinase with a peptide substrate and ATP in the presence of varying concentrations of the inhibitor. The extent of phosphorylation is measured using techniques such as radioactive labeling or fluorescence-based detection. The IC50 values for inhibition of different EGFR mutants (e.g., L858R, T790M) are determined from dose-response curves.
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| Cell Assay |
Cellular activity of AZD9291DA can be evaluated using NSCLC cell lines that harbor specific EGFR mutations, such as the L858R/T790M double mutant. Cells are treated with increasing concentrations of the compound for a defined period, and cell viability is measured using assays like MTT or CellTiter-Glo. The compound's ability to inhibit EGFR phosphorylation in these cells can be assessed by Western blotting using phospho-specific EGFR antibodies. The IC50 values for cell growth inhibition are calculated.
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| Animal Protocol |
In vivo efficacy of AZD9291 or its analogues is typically evaluated in xenograft mouse models using NSCLC cell lines with EGFR mutations. Tumor-bearing mice are treated with the compound via oral administration at various doses. Tumor size is measured regularly using calipers, and the tumor growth inhibition (TGI) is calculated. Body weight and overall health are monitored to assess tolerability.
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| ADME/Pharmacokinetics |
AZD9291DA has a molecular formula of C25H31N7O, a molecular weight of 445.56, and a logP of 2.17, indicating moderate lipophilicity. It is a solid powder with a density of 1.2±0.1 g/cm3. The compound has 2 hydrogen bond donors and 7 acceptors.
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| Toxicity/Toxicokinetics |
AZD9291 (Osimertinib), the parent compound of AZD9291DA, is well tolerated in animal models. The des-acryl analogue is expected to have a similar toxicity profile, although specific toxicology data for AZD9291DA itself is not detailed in the available literature. As a third-generation EGFR inhibitor, it is designed to spare wild-type EGFR, which is expected to reduce the skin rash and gastrointestinal side effects commonly associated with earlier EGFR inhibitors.
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| References |
: Patent WO 2013014448 A1. 2 - (2, 4, 5 - substituted -anilino) pyrimidine derivatives as egfr modulators useful for treating cancer; Targeting resistance in lung cancer. Cancer Discov. 2013 Dec;3(12):OF9. doi: 10.1158/2159-8290.CD-ND2013-025. Epub 2013 Nov 7. PubMed PMID: 24327718.
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| Additional Infomation |
AZD9291DA is a research compound and an intermediate for the design of mutant EGFR inhibitors. It is a des-acryl analogue of AZD9291 (Osimertinib), a third-generation EGFR inhibitor that has been approved for the treatment of NSCLC. AZD9291DA is not a drug itself but a useful tool for medicinal chemistry and drug discovery efforts targeting resistant EGFR mutations.
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| Molecular Formula |
C25H31N7O
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|---|---|
| Molecular Weight |
445.56
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| Exact Mass |
445.259
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| CAS # |
1421372-66-8
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| PubChem CID |
78358313
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| Appearance |
Solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
676.5±65.0 °C at 760 mmHg
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| Flash Point |
363.0±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.635
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| LogP |
2.17
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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 |
8
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| Heavy Atom Count |
33
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| Complexity |
607
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HTNTZPBKKCORTP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H31N7O/c1-30(2)12-13-31(3)23-15-24(33-5)21(14-19(23)26)29-25-27-11-10-20(28-25)18-16-32(4)22-9-7-6-8-17(18)22/h6-11,14-16H,12-13,26H2,1-5H3,(H,27,28,29)
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| Chemical Name |
1-N-[2-(dimethylamino)ethyl]-5-methoxy-1-N-methyl-4-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,2,4-triamine
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| Synonyms |
AZD9291DA AZD9291 DA AZD9291-DA AZD-9291-DA
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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 : ≥ 75 mg/mL (~168.33 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 | 2.2444 mL | 11.2218 mL | 22.4437 mL | |
| 5 mM | 0.4489 mL | 2.2444 mL | 4.4887 mL | |
| 10 mM | 0.2244 mL | 1.1222 mL | 2.2444 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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