Osimertinib, Methanesulfonate Salt (AZD9291, Mereletinib, Tagrisso, CAS 1421373-66-1), >99%

LC Laboratories' Product Number O-7233 - Osimertinib, Methanesulfonate Salt (AZD9291, Mereletinib, Tagrisso, CAS 1421373-66-1), >99% - for research use only. Osimertinib, also known as AZD9291, is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). EGFR TKIs have been used to treat patients with non-small-cell lung cancer (NSCLC) harboring sensitizing mutations. However, resistance develops in many patients, mainly because of the T790M mutation leading to disease progression. Furthermore, EGFR wild type receptor inhibition inherent with these EGFR TKIs can lead to dose-limiting toxicities. Osimertinib is an early, mutant selective, irreversible inhibitor of both EGFR mutant (EGFRm+) sensitizing and T790M resistance mutations with selectivity over the wild type form of the receptor. This research compound is the free base form of osimertinib. We also soon offer the methanesulfonate salt and dimethansulfonate salt forms; please see Osimertinib, Methanesulfonate Salt, Cat. No. O-7233 and Osimertinib, Dimethanesulfonate Salt Cat. No. O-7266. Osimertinib inhibited EGFR phosphorylation in EGFR-bearing cells harboring sensitizing EGFR mutants with mean IC50 values ranging from 13 to 54 nM. It also potently inhibited phosphorylation of EGFR in T790M+ mutant cell lines, with mean IC50 potency less than 15 nM. However, it was less potent at inhibiting phosphorylation of EGFR in wild-type cell lines with mean IC50 range of 480 to 1,865 nM. Osimertinib demonstrated profound and sustained tumor regression in EGFR-mutant tumor xenograft and transgenic models. The clinical activities of osimertinib were initially confirmed with the treatment of two patients with advanced EGFRm(+) T790M(+) non-small-cell lung cancer (NSCLC). A phase I clinical study showed that osimertinib had robust efficacy in EGFR mutant NSCLC patients with acquired resistance to EGFR-TKIs. Overall response rate (ORR) was 51%. The ORR was 64% in 89 EGFR T790M positive patients and 23% in 43 EGFR T790M negative patients. The overall disease control rate was 96% in T790M positive patients. It was well tolerated. Osimertinib is the active ingredient in the drug product sold under the trade name Tagrisso®. This drug is currently approved in at least one country for use in patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC). NOTE: THE OSIMERTINIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT TAGRISSO®, AND IS NOT FOR HUMAN USE. This osimertinib product is the free base, whose CAS number is 1421373-65-0. The CAS number of the methanesulfonate salt form is 1421373-66-1 and a CAS number for the dimethansulfonate salt form has not been assigned as of March 2, 2016. Another CAS number previously assigned to Osimertinib, namely 1610419-47-0, has been deleted by CAS and is no longer in use.

• Supplier: LC Laboratories
• Product #: O-7233
• Sku #: O-7233_200mg