An active metabolite of AZ 9291
AZ 7550 is an active metabolite of AZ 9291 .1 It inhibits the insulin-like growth factor 1 receptor (IGF-1R) in a cell-free assay (IC50 = 1.6 ?M). It inhibits EGFR autophosphorylation in H1975 and PC-9 cells expressing the respective constitutively active mutants EGFRT790M/L858R and EGFRExon19del (IC50s = 0.045 and 0.026 ?M, respectively), as well as in LoVo cells expressing wild-type EGFR (IC50 = 0.786 ?M).
1.Finlay, M.R., Anderton, M., Ashton, S., et al.Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptorJ. Med. Chem.57(20)8249-8267(2014)
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Kinase experiment: |
Biochemical enzyme profiling of AZD9291 and active metabolites across the kinome panel (single profiling experiment representative of two independent studies). % inhibition for kinases in the ~280 kinase panel that shows greater than 60% inhibition after 1 μM treatment with AZD9291, AZ5104 or AZ7550, and follow-up IC50s where tested, are shown. Kinases with a conserved cysteine in the analogous position within their catalytic domain as Cys797 in EGFR are also shown, highlighted in bold[1]. |
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参考文献: [1]. Finlay MR, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249-67. |
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