AZD-9291

详情

AZD***1,AZD***1,
CAS No.:*********0,

AZD***1 is a thirdgeneration EGFR inhibitor, showed promise in preclinical studies and provides hope for patients with advanced lung cancers that have become resistant to existing EGFR inhibitors. AZD***1 is highly active in preclinical models and is well tolerated in animal models. 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.

AZD***1 potently inhibits EGFR phosphorylation in EGFRm+ (e.g. PC9; < *5 nM) and EGFR m+/T**0M (e.g. H***5; < *5 nM) cell lines in vitro, whilst demonstrating much less activity against wildtype EGFR lines (e.g. LoVo; > **0 nM). Consistently, AZD***1 showed significantly more potent inhibition of proliferation in mutant EGFR cell lines compared to wildtype in vitro.
 

CAS#: *********0

Chemical Formula: C*8H*3N7O2
Exact Mass: **9.****7
Molecular Weight: **9.****2
Elemental Analysis: C, *7.*1; H, 6.*6; N, *9.*2; O, 6.*0

 

AZD***1 is an irreversible inhibitor of mutant EGFR kinase with IC*0 values of *5nM, *7nM and **0nM, respectively for L**8R/T**0M, ex*9del and wildtype EGFR [1].

A series of mutations cause the resistance of EGFR, AZD***1 is developed for an irreversible and selective inhibitor of the mutant EGFR. AZD***1 binds to the ATP binding site of EGFR by targeting Cys **7. In EGFR recombinant enzyme assay, AZD***1 shows about **0 times greater potency against the mutant EGFR than wildtype EGFR. AZD***1 does not exhibit significant activity towards other receptor kinase. In vitro assays show that AZD***1can inhibit EGFR phosphorylation with lower IC*0 value in cell lines harboring sensitising EGFR mutants than in wildtype cell lines. Additionally, AZD***1 can induce profound shrinkage in mutant EGFR at low doses in xenograft models. This also happens in transgenic mouse tumor models. Mice treated with AZD***1 at the dose of 5 mg/kg/day display *0% reduction in tumor volume