AZD9291 is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR, respectively. In vivo, AZD9291 shows significantly more potent inhibition of proliferation in mutant EGFR cell lines when compared with wild-type. AZD9291(5mg/kg p.o.) causes profound regression of tumors across EGFRm+ (PC9) and EGFRm+/T790M (H1975) tumor models with profound inhibition of EGFR phosphorylation and key downstream signaling pathways such as AKT and ERK .
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HJM-561, a Potent, Selective, and Orally Bioavailable EGFR PROTAC that Overcomes Osimertinib-Resistant EGFR Triple Mutations
AZD9291 (Osimertinib) purchased from AbMole
Chem Res Toxicol. 2021 Nov 15;34(11):2309-2318.
Quantification of Osimertinib and Metabolite–Protein Modification Reveals Its High Potency and Long Duration of Effects on Target Organs
AZD9291 (Osimertinib) purchased from AbMole
Bioengineered. 2021 Dec;12(1):8679-8689.
AZD3759 inhibits glioma through the blockade of the epidermal growth factor receptor and Janus kinase pathways
AZD9291 (Osimertinib) purchased from AbMole
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AZD3759 enhances radiation effects in non-small-cell lung cancer by a synergistic blockade of epidermal growth factor receptor and Janus kinase-1
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Clin Cancer Res. 2018 Nov 15;24(22):5658-5672.
Increased Synthesis of MCL-1 Protein Underlies Initial Survival of EGFR-Mutant Lung Cancer to EGFR Inhibitors and Provides a Novel Drug Target.
AZD9291 (Osimertinib) purchased from AbMole
Cell Experiment | |
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Cell lines | PC-9, H1975, LOVO, H1650 and H3255 lines |
Preparation method | In vitro EGFR phosphorylation assays Cells were treated for 2 h with a dose-response of each drug. Wild-type cells were stimulated for 10 minutes with 25 ng/ml of EGF before lysis. Level of EGFR phosphorylation was quantified in cell extracts using a modified R&D Systems DuoSet Human phospho-EGFR ELISA (36). |
Concentrations | 0-1000nM |
Incubation time | 2h |
Animal Experiment | |
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Animal models | PC-9 and H1975 cells subcutaneous xenograft models |
Formulation | not mentioned |
Dosages | 5 mg/kg/day QD |
Administration | oral |
Molecular Weight | 499.61 |
Formula | C28H33N7O2 |
CAS Number | 1421373-65-0 |
Solubility (25°C) | DMSO 90 mg/mL (Need warming and ultrasonic) |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[1] Xiao-E Yan, et al. Structural Basis of AZD9291 Selectivity for EGFR T790M
[4] Pasi A Jnne, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer
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