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Description: Osimertinib (formerly AZD-9291 and mereletinib; trade name Tagrisso) is an oral bioavailable, irreversible/covalent, and mutant-selective EGFR inhibitor with potential antineoplastic activity. It inhibits Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR in LoVo cells with IC50s of 12.92, 11.44 and 493.8 nM, respectively. It was approved in 2017 by both FDA and the European Commission for cancer treatment.
References: Transl Lung Cancer Res. 2014 Dec;3(6):370-2; J Med Chem. 2014 Oct 23;57(20):8249-67.
Related CAS: 1421372-66-8(AZD9291 DA - the des acryl derivative of AZD9291); 1421373-66-1 (mesylate); 1421373-65-0 (free base)
Chemical Name: N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide
InChi Key: DUYJMQONPNNFPI-UHFFFAOYSA-N
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)
SMILES Code: C=CC(NC1=CC(NC2=NC=CC(C3=CN(C)C4=C3C=CC=C4)=N2)=C(OC)C=C1N(CCN(C)C)C)=O
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: AZD9291 shows significantly more potent inhibition of proliferation in mutant EGFR cell lines compared to wild-type in vitro.
Kinase Assay: Osimertinib (formerly known as AZD-9291 and mereletinib) is an oral available, irreversible, and mutant-selective, 3rd generation EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR in LoVo cells, respectively. It inhibits both activating and resistant EGFR mutations while sparing the normal form of EGFR that is present in normal skin and gut cells, thereby reducing the side effects encountered with currently available medicines.
Cell Assay: AZD9291 potently inhibits EGFR phosphorylation in EGFRm+ (e.g. PC9; < 25 nM) and EGFR m+/T790M (e.g. H1975; < 25 nM) cell lines in vitro, whilst demonstrating much less activity against wild-type EGFR lines (e.g. LoVo; > 500 nM). Consistently, AZD9291 showed significantly more potent inhibition of proliferation in mutant EGFR cell lines compared to wild-type in vitro.
Purity ≥98%
COA
MSDS
NMR
AZD9291 binding mode and structure. Cancer Discov. 2014 Sep;4(9):1046-61.
Effect of AZD9291 on EGFR phosphorylation in vitro. Cancer Discov. 2014 Sep;4(9):1046-61.
In vivo anti-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.