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AZD9291 (Osimertinib)

Cat. No. M2424
AZD9291 (Osimertinib) Structure
Synonym:

Osimertinib; Mereletinib

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
5mg USD 32  USD40 In stock
10mg USD 44  USD55 In stock
50mg USD 72  USD90 In stock
100mg USD 88  USD110 In stock
200mg USD 104  USD130 In stock
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Quality Control
Biological Activity

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 .

Product Citations
Customer Product Validations & Biological Datas
Source Clinical Cancer Research (2018 Nov). Figure 1. osimertinib (Abmole Bioscience)
Method Western Blot
Cell Lines EGFR mutant NSCLC cell lines
Concentrations 50 nM
Incubation Time 72 h
Results In both sets of DTCs, other than BCL-2 in the PC9 osimertinib-DTCs, other anti-apoptotic BCL-2 family members were not upregulated, and, with the exception of NOXA in the HCC827 gefitinib-DTCs, expression of the key pro-apoptotic BCL-2 family members BIM and NOXA was not markedly diminished.
Source Nat Med (2015). Figure 1. AZD9291
Method digital PCR (ddPCR) assay
Cell Lines Ba/F3 cells
Concentrations 1.0 μM
Incubation Time 72 h
Results Although a more comprehensive analysis of plasma and biopsy tissue collected after resistance develops will be needed to provide greater clarity on C797S mutation incidence, the emergence of this mutation in a marked proportion of AZD9291-resistant patients suggests that development of targeted therapies with the ability to overcome the C797S mutation is warranted.
Protocol
Cell Experiment
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
Animal models PC-9 and H1975 cells subcutaneous xenograft models
Formulation not mentioned
Dosages 5 mg/kg/day QD
Administration oral
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
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.

Chemical Information
Molecular Weight 499.61
Formula C28H33N7O2
CAS Number 1421373-65-0
Purity 100.0%
Solubility DMSO 90 mg/mL (Need warming and ultrasonic)
Storage at -20°C
References

[1] Xiao-E Yan, et al. Structural Basis of AZD9291 Selectivity for EGFR T790M

[2] Alessandro Leonetti, et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer

[3] Kenneth S Thress, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M

[4] Pasi A Jnne, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer

[5] Darren A E Cross, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer

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Keywords: AZD9291 (Osimertinib), Osimertinib; Mereletinib supplier, EGFR/HER2, inhibitors

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