| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Osimertinib (formerly AZD-9291 and mereletinib; trade name Tagrisso) is an oral bioavailable, irreversible/covalent, and mutant-selective EGFR inhibitor with potential antineoplastic activity. In LoVo cells, it inhibits WT EGFR, L858R/T790M EGFR, and Exon 19 deletion EGFR with IC50 values of 493.8 nM, 11.44, and 12.92 nM, respectively. Both the FDA and the European Commission approved it in 2017 for the treatment of cancer.
| Targets |
EGFRL858R (IC50 = 12 nM); EGFRL858R/T790M (IC50 = 1 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
In Corning black, clear-bottomed 384-well plates, 10,000 cells are seeded per well in growth medium, and the plates are then incubated for an entire night at 37°C with 5% CO2. Compounds are serially diluted in 100% DMSO and used to acoustically dose cells using an Echo 555. After aspirating the medium and incubating the plates for an additional two hours, 40μL of lysis buffer is added to each well. Greiner black high bind 384-well plates are blocked with 3% BSA after being coated with capture antibody. After the block is removed, 15μL of lysate is added to the Greiner black high bind 384-well plates, and the plates are incubated for two hours. Detection antibody (20μL) was added and the plates were incubated for two hours after aspiration and PBS washing. Aspiration and PBS washing are followed by the addition of 20μL of QuantaBlu fluorogenic peroxidase substrate and an hour of incubation. Add 20μL of QuantaBlu stop solution to each plate, and use an Envision plate reader to read the fluorescence at 352 nm for excitation and 460 nm for emission. A suitable software program is used to export the data obtained with each compound and perform curve fitting analysis. By calculating the compound concentration necessary to produce a 50% effect, an IC50 value is obtained from this data.
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| Cell Assay |
In vitro, AZD9291 shows significant suppression of EGFR phosphorylation in EGFRm+ (e.g., PC9; < 25 nM) and EGFR m+/T790M (e.g., H1975; < 25 nM) cell lines, but much less activity against wild-type EGFR lines (e.g., LoVo; > 500 nM). In vitro, AZD9291 continuously demonstrated a much more powerful suppression of proliferation in mutant EGFR cell lines when compared to wild-type.
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The median time to Cmax was found to be 6 hours. Osimertinib is primarily eliminated through excretion in the feces (68%), to a lesser extent through urine (14%), while only 2% is excreted unchanged. The mean volume of distribution at steady state is 918 L. Oral clearance is 14.3 L/hr. Metabolism / Metabolites Osimertinib is metabolized to at least two pharmacologically active metabolites, AZ7550 and AZ5104, that circulate at approximately 10% of the concentration of the parent compound. Biochemical assays have shown that AZ7550 has similar potency and efficacy to osimertinib, while AZ5104 is more potent against mutant and wild-type EGFR. The main metabolic pathways are oxidation (predominantly by CYP3A) and dealkylation. Biological Half-Life The population estimated mean half-life is 48 hours. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
Elevations in serum aminotransferase levels are uncommon during osimertinib therapy occurring in 4% to 5% of patients and rising above 5 times the upper limit of the normal range in only 1% or less. In preregistration trials, there was a single incidence of clinically apparent liver injury attributed to osimertinib therapy, but the clinical features and relatedness to therapy were not defined. Since its approval and more widespread use, there have been no published cases of liver injury due to osimertinib. Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the clinical use of osimertinib during breastfeeding. Because osimertinib is 95% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is about 48 hours and it might accumulate in the infant. The drug also has 2 active metabolites that have not been studied in breastmilk. The manufacturer recommends that breastfeeding be discontinued during osimertinib therapy and for 2 weeks after the final dose. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Plasma protein binding of osimertinib is 95%. |
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| References |
[1]. Patent. 2013, WO2013014448 A1. [2]. Mol Cancer Ther (2013) 12 (11_Supplement): A109. [3]. Sci Transl Med. 2022 Mar 30;14(638):eabc7480. [4]. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.[5]. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistancemutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249-67. |
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| Additional Infomation |
Pharmacodynamics
A pharmacokinetic/pharmacodynamic analysis suggested a concentration-dependent QTc interval prolongation of 14 msec (upper bound of two-sided 90% CI: 16 msec) at a dose of osimertinib 80 mg. |
| Molecular Formula |
C28H33N7O2
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|---|---|
| Molecular Weight |
499.61
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| Exact Mass |
499.269
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| Elemental Analysis |
C, 67.31; H, 6.66; N, 19.62; O, 6.40
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| CAS # |
1421373-65-0
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| Related CAS # |
Osimertinib mesylate;1421373-66-1;Osimertinib-d6;1638281-44-3;Osimertinib dimesylate;2070014-82-1;Osimertinib-13C,d3;2254100-49-5
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| PubChem CID |
71496458
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| Appearance |
Brown to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.618
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| LogP |
3.3
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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 |
10
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| Heavy Atom Count |
37
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| Complexity |
752
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])[H])C1=C(C([H])=C(C(=C1[H])N(C([H])([H])[H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])N([H])C(C([H])=C([H])[H])=O)N([H])C1=NC([H])=C([H])C(C2=C([H])N(C([H])([H])[H])C3=C([H])C([H])=C([H])C([H])=C32)=N1
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| InChi Key |
DUYJMQONPNNFPI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H33N7O2/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32)
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| Chemical Name |
N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide
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| Synonyms |
AZD-9291; AZD9291; AZD 9291; Mereletinib; AZD9291; AZD 9291; UNII-3C06JJ0Z2O; Osimertinib [USAN]; Osimertinib free base; Mereletinib; Trade name: Tagrisso
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.00 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.16 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. Solubility in Formulation 4: 1% DMSO+30% PEG 300+dd H2O: 30mg/mL Solubility in Formulation 5: 5 mg/mL (10.01 mM) in 0.5%HPMC 1%Tween80 (add these co-solvents sequentially from left to right, and one by one), Suspened solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0016 mL | 10.0078 mL | 20.0156 mL | |
| 5 mM | 0.4003 mL | 2.0016 mL | 4.0031 mL | |
| 10 mM | 0.2002 mL | 1.0008 mL | 2.0016 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.
Study of Precision Treatment for Rare Tumours in China Guided by PDO and NGS
CTID: NCT06692491
Phase: Phase 2 Status: Not yet recruiting
Date: 2024-11-18
AZD9291 binding mode and structure.Cancer Discov.2014 Sep;4(9):1046-61. |
Effect of AZD9291 on EGFR phosphorylationin vitro.Cancer Discov.2014 Sep;4(9):1046-61. |
In vivoanti-tumor efficacy of AZD9291 in subcutaneous xenograft models of EGFR-TKI sensitising and T790M resistant lung cancer.Cancer Discov.2014 Sep;4(9):1046-61. |
AZD9291 induces significant and sustained tumor regression in transgenic models of EGFR-TKI sensitising (C/L858R) and T790M resistant (C/L+T) lung cancer.Cancer Discov.2014 Sep;4(9):1046-61. |
AZD9291 inhibits EGFR phosphorylation and downstream signallng in murine models of EGFR T790M resistant lung cancer.Cancer Discov.2014 Sep;4(9):1046-61. |
Proof of concept clinical studies validating AZD9291 as a mutant-selective EGFR kinase T790M inhibitor.Cancer Discov.2014 Sep;4(9):1046-61. |
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