AZD-9291 mesylate

A potent, selective, third-generation irreversible inhibitor of mutant EGFR with IC50s of 1/12/5 nM for L858R-T790M/L858R/L861Q respectively; weak activity against wt EGFR (IC50=184 nM) ; inhibits signaling pathways and cellular growth in both EGFRm (+) and EGFRm (+) /T790M (+) mutant cell lines in vitro; exhibits tumor regression in EGFR-mutant tumor xenograft and transgenic models; orally active.Lung Cancer Approved (In Vitro) :Osimertinib (AZD-9291) shows similar potency to early generation tyrosine kinase inhibitor (TKIs) in inhibiting EGFR phosphorylation in EGFR cells harboring sensitising EGFR mutants including PC-9 (ex19del), H3255 (L858R) and H1650 (ex19del), with mean IC50 values ranging from 13 to 54 nM for Osimertinib. Osimertinib (AZD-9291) also potently inhibits phosphorylation of EGFR in T790M mutant cell lines (H1975 (L858R/T790M), PC-9VanR (ex19del/T790M), with mean IC50 potency less than 15 nM. (In Vivo) :The tumor-bearing mice are treated with Osimertinib (AZD-9291) (5 mg/kg/day) for one to two weeks. Within days of treatment, 5 of 5 C/L858R mice displays nearly 80% reduction in tumor volume by magnetic resonance imaging MRI after therapy with Osimertinib, while 5 of 5 mice treated with vehicle shows tumor growth. Osimertinib (AZD-9291) demonstrates improved rat PK, reduced hERG affinity, and improved IGF1R margins relative to the previously described compounds, and so this compound is selected for further investigation. Osimertinib (AZD-9291) also offers an additional degree of broader chemical and profile diversity when compared to the previously described lead compounds. Upon dosing Osimertinib (AZD-9291) in three efficacy models, The comparable efficacy is observed at relatively low doses (10 mg/kg per day) . The excellent efficacy is also observed when Osimertinib (AZD-9291) is dosed at 5 mg/kg per day.

1421373-66-1

Osimertinib mesylate | Mereletinib mesylate | AZD9291 mesylate | AZD 9291 mesylate

>98% (HPLC)

DMSO

CN1C=C (C2=CC=CC=C21) C3=NC (=NC=C3) NC4=C (C=C (C (=C4) NC (=O) C=C) N (C) CCN (C) C) OC.CS (=O) (=O) O

C29H37N7O5S

595.713

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.