AZ5104 |
| カタログ番号GC12955 |
AZ5104 は、AZD 9291 の活性な脱メチル化代謝物です。AZ5104 は、EGFRL858R/T790M、EGFRL858R、EGFRL861Q、EGFR、および ErbB4 に対してそれぞれ 1、6、1、25、および 7 nM の IC50 を持つ EGFR 阻害剤です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1421373-98-9
Sample solution is provided at 25 µL, 10mM.
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AZ5104, is the demethylated metabolite of AZD-9291,is a potent EGFR inhibitor. IC50 <1 nM, 6 nM, 1 nM, 25 nM, for EGFR (L858R/T790M), EGFR (L858R), EGFR (L861Q), and EGFR (wildtype), respectively.
EGFR (epidermal growth factor receptor) is a receptor tyrosine kinase on the cell surface. The receptor activation leads to dimerization and tyrosine autophosphorylation. It induces downstream cellular responses such as modification in gene expression, cell proliferation and cytoskeletal rearrangement etc.
Compare to AZD9291, AZ5104 has somewhat more potency in mutant EGFR cell lines ex19del (2 nmol/L in PC-9), T790M (2 nmol/L in H1975), and wild-type EGFR (33 nmol/L in LOVO) cell lines. In a phenotypic assay, AZ5104 showed a greater potency across cell lines in a phenotypic assay.
3 hours after oral dosing in the mouse, the circulating active metabolites in plasma is 33% for AZ5104. In both C/L858R and C/L+T mice, 5 mg/kg/day dose of AZ5104, also show efficacy in shrinking tumors.
Reference:
1. Cross DA, Ashton SE, Ghiorghiu S 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.
Average Rating: 5 (Based on Reviews and 15 reference(s) in Google Scholar.)
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