Rezivertinib is an orally active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) developed for EGFR-mutated non-small cell lung cancer (NSCLC). It is also known by the development code BPI-7711. Rezivertinib irreversibly inhibits mutant EGFR, including the acquired resistance mutation EGFR T790M, while retaining activity against common activating EGFR mutations.
The free-base active substance is identified by CAS No. 1835667-12-3, molecular formula C27H30N6O3, and molecular weight 486.57 g/mol. These identifiers are supported by PubChem and the FDA Global Substance Registration System.
China's NMPA announced marketing approval of Rezivertinib Mesylate Capsules for adults with locally advanced or metastatic NSCLC with disease progression after prior EGFR-TKI therapy and confirmed EGFR T790M mutation.
Rezivertinib is a small-molecule EGFR inhibitor containing an acrylamide pharmacophore and substituted aminopyrimidine/indole structural features. Its systematic name is:
N-[2-[2-(dimethylamino)ethoxy]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide.
PubChem reports a monoisotopic molecular weight of 486.24 Da and the molecular formula C27H30N6O3.
The free base should be distinguished from the pharmaceutical Rezivertinib mesylate and other salt forms. The hydrochloride is separately identified as CAS 2170255-78-2, formula C27H31ClN6O3 and molecular weight 523.03 g/mol. Therefore, API documentation should clearly state the exact form being supplied.
Rezivertinib mesylate has been approved in China for adults with locally advanced or metastatic NSCLC with EGFR T790M mutation following disease progression during or after prior EGFR-TKI therapy.
Clinical studies have demonstrated activity in patients with EGFR T790M-mutated advanced NSCLC. In a phase 2b study of 226 patients, blinded independent central review reported an objective response rate of 64.6%, disease control rate of 89.8%, and median progression-free survival of 12.2 months.
Earlier phase 1 development evaluated once-daily oral doses ranging from 30 mg to 300 mg in patients with advanced NSCLC carrying EGFR T790M mutations.
Rezivertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor. It preferentially inhibits mutant EGFR, including common activating mutations and the acquired resistance mutation T790M, while showing substantially lower activity against wild-type EGFR.
The irreversible inhibition is associated with its acrylamide-containing structure, which enables covalent interaction with the kinase domain. Blocking mutant EGFR signaling suppresses downstream pathways involved in tumor-cell proliferation and survival.
Preclinical studies reported cellular GI50 values of approximately 13.3 nM in PC9 cells with EGFR exon 19 deletion, 6.8 nM in HCC827 cells with L858R, and 22 nM in NCI-H1975 cells carrying del19/T790M. Activity against EGFR wild-type A431 cells was substantially weaker, with GI50 greater than 1,000 nM.
Quality control for Rezivertinib API may include:
Commercial analytical reference material is reported as a solid and has been characterized using chromatographic and spectroscopic techniques. Cayman Chemical reports ≥98% purity for its analytical product, while other commercial analytical material has reported higher batch-specific purity. These values should not be treated as universal pharmaceutical API release specifications.
Rezivertinib is a synthetic small-molecule API requiring controlled chemical synthesis, purification and isolation of the desired solid form. Manufacturing controls should address reaction completion, process-related impurities, degradation products, residual solvents, elemental impurities and solid-state characteristics.
Particular care should be taken to distinguish the free base from the mesylate salt used in the approved pharmaceutical product. The exact salt form, stoichiometry and manufacturing specification should be stated in the API documentation.
| Property | Verified Value |
|---|---|
| Appearance | Solid; commercial analytical material reported white to yellow |
| Molecular Formula | C27H30N6O3 |
| Molecular Weight | 486.57 g/mol |
| CAS Number | 1835667-12-3 |
| Exact / Monoisotopic Mass | 486.24 Da |
| PubChem CID | 118912975 |
| FDA UNII | U65F5M6BD5 |
| Development Code | BPI-7711 |
| Physical Form | Solid |
| Key Target | Mutant EGFR |
| Key Resistance Mutation | EGFR T790M |
| Route | Oral |
The molecular identity and molecular weight are supported by PubChem and FDA GSRS. Commercial analytical sources describe the material as a solid.
For bulk Rezivertinib API, packaging should provide suitable protection against moisture, contamination and inappropriate environmental exposure.
Commercial analytical reference material is supplied as a solid and commonly stored under controlled low-temperature conditions. Cayman Chemical specifies −20°C for its analytical material, while other commercial reference material provides storage recommendations according to the individual certificate of analysis. These conditions should not automatically be adopted as the universal pharmaceutical API storage requirement.
The API storage condition should ultimately be established from validated stability data and the applicable manufacturing specification.
Typical documentation for Rezivertinib API may include:
A qualified Rezivertinib API manufacturer in India should maintain robust controls over synthetic processing, purification, impurity management and solid-state quality.
For Rezivertinib, particular attention should be given to the exact API form because the free base and pharmaceutical salt forms have different molecular compositions and molecular weights. Comprehensive analytical characterization is important for ensuring consistent pharmaceutical quality.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.50% |