AZD-9291 mesylate

Product name: Osimertinib mesylate

Product synonyms: AZD-9291(Mesylate);N-[2-[[2-(Dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-propenamidemethanesulfonate(1:1);AZD-9291mesylateN-[2-[[2-(Dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-propenamidemethanesulfonate(1:1);Osimertinib;N-[2-(2-dimethylaminoethylmethylamino)-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamidemesylatesalt;OsimertinibMesylate(AZD9291);Osimertinibmesylate;Mereletinibmesylate

CAS NO: 1421373-66-1

Molecular formula: C29H37N7O5S

Molecular weight: 595.72

Melting point >232°C(dec.)

Storage condition -20°C Freezer, Under inert atmosphere

Solubility DMSO(Slightly), Methanol(Slightly)

Appearance Solid

Color Off-White to Yellow

New drug for non-small cell lung cancer - Osimertinib

On November 13, 2015, the US FDA approved the launch of AstraZeneca's new drug Osimertinib (Osimertinib) oral tablets from the UK through the priority review pathway, with the trade name Tagrisso. For the treatment of patients with advanced non-small cell lung cancer who have epidermal growth factor receptor (EGFR) T790M mutation or are resistant to other EGFR inhibitors. Before clinical use of the EGFR inhibitor osimertinib, patients must first be tested for T790M mutation. Only patients with T790M-mutated non-small cell lung cancer can use osimertinib for targeted treatment.

Osimertinibmesylate (AZD9291) is the mesylate form of osimertinib and is an oral third-generation epidermal growth factor receptor (EGFR) tyrosine kinase (TKI) inhibitor.

Osimertinib is active against exon 19 deletions, exon 21 mutations, and also the exon 20 T790M mutations. It is preferentially selective for mutated EGFR, and therefore toxicity at therapeutic doses is lower than for first- and second-generation agents. Notably, osimertinib is able to cross the blood-brain barrier, making it active against disease in the CNS.

AZD-9291 Mesylate is a potent and selective epidermal growth factor receptor (EGFR) inhibitor.

ChEBI: A methanesulfonate (mesylate) salt prepared from equimolar amounts of osimertinib and methanesulfonic acid. Used for treatment of EGFR T790M mutation positive non-small cell lung cancer.

The collection of ibrutinib (Imbruvica(R), Pharmacyclics Inc.), afatinib, and osimertinib represents the small, yet expanding, group of covalent SMKIs. Ibrutinib is a non-receptor Bruton’s tyrosine kinase inhibitor approved for the treatment of relapsed chronic lymphocytic leukemia. Afatinib, approved for NSCLC in 2013 and squamous NSCLC in 2016, is a second-generation irreversible EGFR inhibitor that targets wild-type EGFR, the mutant T790M EGFR, and HER2. Osimertinib (AZD9291), which was approved by FDA in November 2015, is a third-generation irreversible EGFR inhibitor that selectively targets the mutant T790M EGFR. Rociletinib, which shares a high degree of structural similarity with that of osimertinib, is a promising covalent EGFR inhibitor developed by Clovis Oncology aimed for the treatment of patients with EGFR T790M-mutated NSCLC, until the company terminated its development in May 2016 following a negative vote fromthe FDA’sOncologic Drugs Advisory Committee.

Osimertinib toxicity is dose-dependent and is associated with fewer gastrointestinal and dermatologic adverse events than with other approved EGFR TKIs.