Antitumor 99% Raw Powder Azd-9291 with 99% Purity CAS 1421373-65-0

Quick Detail:

AZD 9291 Main Function:

AZD 9291 is an irreversible inhibitor of epidermal growth factor receptor (EGFR) sensitizing and T790M
resistance mutations (IC50s = 15-17 nM) while sparing the wild-type form of the receptor (IC50 = 480 nM). It binds the related IGF1R and hERG receptors with significantly reduced potency (IC50s = 2.9 and 16.2 μM, respectively). AZD 9291 has been shown to inhibit tumor growth in a xenograft mouse model at oral doses of 5-10 mg/kg and has been tested clinically in patients with advanced EGFR mutant non-small-cell lung cancer.

AZD-9291 Application:

AZD9291 administered once daily orally at 5 mg/kg caused profound regression of tumours across EGFRm+ (PC9; 178% growth inhibition) and EGFRm+/T790M (H1975; 119% growth inhibition) tumour models in vivo, after 14 days dosing. Furthermore 5 mg/kg AZD9291 was sufficient to cause significant shrinkage of EGFRm+ and EGFRm+/T790M transgenic mouse lung tumours.

Tumour growth inhibition was associated with profound inhibition of EGFR phosphorylation and key downstream signaling pathways such as AKT and ERK. Chronic long-term treatment of PC9 and H1975 xenograft tumours with AZD9291 led to a complete and sustained macroscopic response, with no visible tumours after 40 days dosing, and being maintained beyond 100 days. Furthermore, pre-clinical data also indicates that AZD9291 could target tumours that have acquired resistance to the more recently identified HER2-amplification mechanism, thus potentially extending its benefit in TKI resistant patients.

AZD-9291 Usage:

Cell lines.Human lung cancer cells with EGFR-mutations or wild type EGFR stable expression.