Sunvozertinib is a small-molecule EGFR tyrosine kinase inhibitor (TKI) developed for the treatment of non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. It is also known by the development code DZD9008 and is marketed in the United States as ZEGFROVY. FDA granted accelerated approval in 2025 for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
The API has CAS No. 2370013-12-8, molecular formula C₂₉H₃₅ClFN₇O₃, and molecular weight 584.09 g/mol. FDA identifies Sunvozertinib as a single defined R-configured chiral molecule, rather than a salt.
Sunvozertinib is an orally active kinase inhibitor targeting mutant EGFR. FDA describes its mechanism as inhibition of EGFR exon 20 insertion mutations, with greater inhibitory activity against several exon 20 insertion variants than wild-type EGFR in cellular models.
The compound contains a substituted pyrimidine core, chlorofluorophenyl group, dimethylaminopyrrolidine moiety and acrylamide pharmacophore. Its acrylamide functionality contributes to irreversible kinase inhibition through covalent interaction with the kinase target.
The chemical name of Sunvozertinib is N-{5-[(4-[[5-chloro-4-fluoro-2-(1-hydroxy-1-methylethyl)phenyl]amino]pyrimidin-2-yl)amino]-2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-4-methoxyphenyl}prop-2-enamide. FDA confirms one chiral carbon with R-configuration.
PubChem reports the molecular formula as C₂₉H₃₅ClFN₇O₃, molecular weight 584.1 g/mol, exact mass 583.2474 Da and InChIKey BTMKEDDEMKKSEF-QGZVFWFLSA-N.
Sunvozertinib is not a conventional sulfonamide or salt-form API; it is a neutral small-molecule kinase inhibitor. FDA's chemistry review specifically states that the salt-policy assessment was not applicable because the active ingredient is not a salt.
Sunvozertinib is used as an oncology API for targeted treatment of adult patients with locally advanced or metastatic NSCLC carrying EGFR exon 20 insertion mutations. The U.S. indication requires disease progression on or after platinum-based chemotherapy and detection of the mutation using an FDA-approved test. The approval is under the accelerated-approval pathway.
The approved U.S. dosage is 200 mg orally once daily with food. ZEGFROVY is supplied as 150 mg and 200 mg tablets.
Sunvozertinib binds to and inhibits EGFR kinase activity, particularly mutant EGFR containing exon 20 insertion alterations. FDA reports that sunvozertinib inhibits EGFR phosphorylation in cells expressing different EGFR exon 20 insertion variants at approximately 2- to 10-fold lower concentrations than required to inhibit wild-type EGFR signaling in the tested models.
The drug is an irreversible inhibitor because its acrylamide-containing structure enables covalent interaction with the kinase target.
Sunvozertinib is a relatively new oncology API and I could not verify a current USP, BP or Ph. Eur. monograph establishing universal numerical API-release limits for assay, related substances, water, residue on ignition or other conventional CMS parameters.
Therefore, numerical release specifications for these parameters should not be invented. A commercial API specification should be based on the manufacturer's validated analytical procedures, regulatory filing and applicable ICH impurity and elemental-impurity requirements.
FDA's chemistry review confirms that Sunvozertinib is treated as a non-salt active ingredient and identifies the drug substance's chemical and pharmaceutical characteristics.
Manufacturing of Sunvozertinib API involves controlled multi-step organic synthesis, purification and isolation of the required stereochemical form. Since Sunvozertinib contains one stereogenic center and FDA specifies the R-configuration, stereochemical control is an important quality consideration.
Important quality attributes include identity, assay, related substances, stereochemical purity, residual solvents, elemental impurities, water content and solid-state properties where applicable.
FDA reports two basic centers with pKa values of approximately 6.18 and 8.28. FDA's clinical pharmacology review also reports pH-dependent aqueous solubility: equilibrium solubility after 24 hours was >347 mg/mL at pH 1.2, 25.3 mg/mL at pH 4.5, 7.94 mg/mL at pH 5.0, 4.24 mg/mL at pH 5.2, and 3.56 mg/mL at pH 5.5.
Independent chemical-reference data describe Sunvozertinib as insoluble in water, while reporting solubility of approximately 50 mg/mL in DMSO and 6 mg/mL in ethanol at 25°C for a research-grade batch. These solvent-specific values should not be treated as pharmacopoeial release specifications.
Sunvozertinib API should be stored in appropriate pharmaceutical-grade, tightly closed packaging under validated conditions. Protection from moisture, contamination and excessive environmental exposure should be maintained according to the manufacturer's stability data.
A pharmaceutical Sunvozertinib API documentation package may include:
A qualified Sunvozertinib API manufacturer should maintain strict control of the R-configured active substance, chemical purity, related substances, residual solvents and solid-state characteristics. For this newer oncology API, manufacturer-specific specifications should be supported by validated analytical procedures and appropriate regulatory documentation rather than unsupported generic numerical limits.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |