Osimertinib-d₆  (Synonyms: AZD-9291-d₆; Mereletinib-d₆)

Osimertinib-d₆ is a deuterium labeled osimertinib. Osimertinib is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M. Osimertinib overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer[1].

Osimertinib (AZD9291) (0-10 μM; 72 hours) dramatically inhibits cell proliferation with IC₅₀s of 41, 26, 41, and 31 nM, respectively^[2].
Osimertinib (0-10 μM; 72 hours) inhibits cell proliferation (Ba/F3 cells harboring a T790M mutation, exon 19del+T790M, or L858R+T790M) with IC₅₀s of 6, 7, and 74 nM, respectively^[2].
Osimertinib (0-10 μM; 72 hours) inhibits Ba/F3 cells harboring EGFR exon 20 insertion mutations (IC₅₀ ranging from 16-701 nM for A763_Y764insFQEA (FQEA), Y764_V765insHH (HH), A767_V769dupASV (ASV), and D770_N771insNPG (NPG) cells) ^[2].
Osimertinib shows high levels of phenotype potency in both sensitizing-mutant (mean IC₅₀ of 8 nM in PC-9) and T790M (mean IC₅₀ of 11 and 40 nM in H1975 and PC-9VanR respectively) EGFR cell lines. Osimertinib has much less activity towards wild-type EGFR (mean IC₅₀ of 650 and 461 nM in Calu3 and H2073 respectively)^[1].
Osimertinib (0.1 μM; 48 hours) induces apoptosis in Ba/F3 cells (apoptosis rate of 40.9% and 90% in EGFR exon 19del+T790M, EGFR L858R+T790M respectively) ^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Osimertinib (0.1-25 mg/kg; p.o.; daily for 14 day) induces significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

505.64

Solid

C₂₈H₂₇D₆N₇O₂

1638281-44-3

C=CC(NC1=CC(NC2=NC=CC(C3=CN(C)C4=C3C=CC=C4)=N2)=C(OC)C=C1N(CCN(C([2H])([2H])[2H])C([2H])([2H])[2H])C)=O

Room temperature in continental US; may vary elsewhere.

4°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

• [1]. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.  [Content Brief]

  [2]. [2]Hirano T, et al. Pharmacological and Structural Characterizations of Naquotinib, a Novel Third-Generation EGFR Tyrosine Kinase Inhibitor, in EGFR-Mutated Non-Small Cell Lung Cancer. Mol Cancer Ther. 2018 Apr;17(4):740-750.  [Content Brief]