API Osimertinib mesylate

Osimertinib mesylate More Info

Osimertinib mesylate is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) clinically indicated for the treatment of specific non-small cell lung cancer (NSCLC) subtypes. It is designed to target EGFR mutations, including sensitizing mutations and the T790M resistance mutation, with high selectivity. Recognized in major global pharmacopoeial standards, it is utilized as an active pharmaceutical ingredient (API) in oral pharmaceutical formulations approved across multiple regions.​

Key Chemical & Physical Specifications​

Chemical Name: N-(2-{2-(Dimethylamino)ethylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide methanesulfonate​

CAS Number: 1421373-65-0​

Molecular Formula: C₂₈H₃₃N₇O₂ · CH₄O₃S​

Molecular Weight: 615.76 g/mol​

Appearance: White to off-white crystalline powder​

Typical Purity: ≥99.0% (as per HPLC detection, consistent with USP/EP/ChP standards)​

Solubility: Slightly soluble in water, soluble in methanol and dimethyl sulfoxide (DMSO)​

Storage Requirements: Sealed container, stored at 25 ℃ or below, protected from light and moisture (standard storage conditions for stability maintenance; avoid extreme temperature fluctuations)​

Mechanism of Action​

Osimertinib mesylate exerts its therapeutic effect by irreversibly binding to the ATP-binding site of mutant EGFR proteins in NSCLC cells. It specifically targets EGFR mutations such as exon 19 deletions, exon 21 L858R substitutions, and the T790M mutation (a common mechanism of resistance to first-generation EGFR-TKIs). By inhibiting EGFR tyrosine kinase activity, it blocks downstream signaling pathways (e.g., PI3K/Akt, RAS/RAF/MEK) that drive cancer cell proliferation, survival, and metastasis. Its high selectivity for mutant EGFR minimizes off-target effects on wild-type EGFR, reducing certain treatment-related toxicities.​

Clinical Applications & Indications​

Approved for the first-line treatment of metastatic NSCLC in adults whose tumors harbor sensitizing EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations).​

Approved for the treatment of metastatic NSCLC in adults with EGFR T790M mutation-positive tumors, as detected by an FDA/EMA/NMPA-approved test, who have progressed on or after first-line EGFR-TKI therapy.​

Formulated as oral tablets (common strengths include 40 mg and 80 mg); dosage and administration are guided by regional regulatory guidelines, patient weight, and disease status. Efficacy is supported by clinical trials demonstrating improved progression-free survival (PFS) and overall survival (OS) compared to first-generation EGFR-TKIs in selected patient populations, though individual response varies.​

Safety & Considerations​

Adverse reactions reported in clinical use are generally manageable; common events include diarrhea, rash, dry skin, nail toxicity (e.g., onycholysis), and stomatitis.​

Serious adverse events may include interstitial lung disease (ILD)/pneumonitis, QTc interval prolongation, and cardiomyopathy. Prompt medical intervention is required if symptoms of these conditions occur.​

Contraindications include hypersensitivity to osimertinib mesylate or any excipients in the formulation.​

Caution is advised in patients with pre-existing cardiac or pulmonary conditions, as well as those with moderate to severe hepatic or renal impairment (limited data on safety and efficacy in these groups).​

Drug interactions: Concurrent use with strong CYP3A4 inducers may decrease osimertinib exposure; co-administration with drugs that prolong the QTc interval may increase the risk of arrhythmias. Clinical monitoring is recommended when combining with such agents.​

Quality & Regulatory Status​

Manufactured in facilities compliant with Good Manufacturing Practices (GMP) to meet regional regulatory requirements (e.g., FDA, EMA, NMPA).​

Supporting documentation for regulatory submissions (e.g., Certificate of Analysis, Drug Master File, stability data, clinical trial reports) is required to demonstrate compliance with pharmacopoeial standards and therapeutic equivalence.​

Packaging & Supply​

Standard packaging options for API include 1kg/5kg/25kg sealed aluminum foil bags or fiber drums with moisture-proof and light-resistant liners, suitable for long-term storage and international transportation.​

Supply chain and lead times vary by manufacturer; bulk quantities and custom specifications (e.g., particle size, impurity profiles) may be available for research or pharmaceutical production needs.​

Notes​

This information is based on publicly available pharmacopoeial data, phase III clinical trial results (e.g., FLAURA, AURA3), and established pharmaceutical industry standards.​

Clinical use must adhere to regional prescribing guidelines, companion diagnostic testing requirements, and professional medical judgment.​

Ongoing research explores potential applications in other EGFR-mutated cancers or combination therapies with immunotherapies/chemotherapies, with no established clinical indications beyond NSCLC to date.