Ripretinib is a synthetic small-molecule tyrosine kinase inhibitor developed for anticancer therapy. It is primarily associated with the treatment of advanced gastrointestinal stromal tumors (GIST). Ripretinib is characterized as a switch-control kinase inhibitor that targets key signaling pathways involved in tumor growth and survival.
The chemical formula of Ripretinib is C₂₄H₂₁BrFN₅O₂, and its molecular weight is 510.36 g/mol. The established CAS Registry Number is 1442472-39-0. FDA and PubChem records support these chemical identity details.
Ripretinib is an orally active kinase inhibitor designed to inhibit mutant and wild-type forms of KIT and PDGFRA. These receptor tyrosine kinases are important molecular drivers in gastrointestinal stromal tumors.
The FDA describes Ripretinib as a white to off-white crystalline solid. It is a lipophilic weak base and is practically insoluble in aqueous media, an important physicochemical consideration during pharmaceutical formulation development.
| Property | Details |
|---|---|
| API Name | Ripretinib |
| CAS Number | 1442472-39-0 |
| Molecular Formula | C₂₄H₂₁BrFN₅O₂ |
| Molecular Weight | 510.36 g/mol |
| PubChem CID | 71584930 |
| UNII | 9XW757O13D |
| Development Code | DCC-2618 |
| API Type | Synthetic small-molecule API |
| Pharmacological Class | Tyrosine kinase inhibitor |
| Therapeutic Area | Oncology |
| Physical Form | White to off-white crystalline solid |
| Aqueous Solubility | Practically insoluble |
| Primary Targets | KIT and PDGFRA |
The CAS number, PubChem CID, formula and molecular identity are independently supported by PubChem and FDA GSRS.
Ripretinib is used as the active pharmaceutical ingredient in oral anticancer medicines for advanced gastrointestinal stromal tumor (GIST).
The current FDA labeling indicates Ripretinib for adults with advanced GIST who have previously received treatment with three or more kinase inhibitors, including imatinib. The recommended labeled dosage of the finished medicine is 150 mg orally once daily.
The EMA likewise identifies Ripretinib as the active substance in Qinlock for advanced GIST following treatment with three or more kinase inhibitors, including imatinib.
Ripretinib functions as a tyrosine kinase inhibitor. It inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor alpha (PDGFRA), including wild-type forms as well as primary and secondary mutations.
The FDA also reports in-vitro inhibitory activity against other kinases, including PDGFRB, TIE2, VEGFR2 and BRAF.
By inhibiting these kinase signaling pathways, Ripretinib interferes with signaling processes that can contribute to tumor-cell proliferation and survival.
Pharmaceutical-grade Ripretinib API requires comprehensive analytical characterization to establish identity, strength, purity and consistency.
Relevant quality testing may include:
Published analytical research specifically addressing Ripretinib drug substance has identified the need to control certain potential mutagenic process impurities. In one published study, four investigated class-3 potential mutagenic impurities were assigned an acceptable limit of 10 ppm each, based on a 1.5 µg/day threshold and the 150 mg/day maximum dose used in that assessment. This is useful process-impurity information, but it should not be presented as a universal pharmacopoeial API specification.
Ripretinib API manufacturing involves controlled multi-step organic synthesis, followed by appropriate purification, crystallization, isolation and drying operations.
Because Ripretinib contains a defined heterocyclic structure and several functional groups, manufacturing control is important for minimizing starting-material residues, intermediates, process-related impurities and residual solvents.
API production intended for pharmaceutical applications should incorporate appropriate GMP controls, validated analytical procedures, raw-material qualification, impurity control and documented batch-release testing.
Ripretinib is a white to off-white crystalline solid. The FDA characterizes it as lipophilic, a weak base, and practically insoluble in aqueous media.
These properties are relevant to pharmaceutical development because low aqueous solubility can influence dissolution, formulation design and oral drug-product performance.
The molecular weight is 510.36 g/mol, while the molecular formula is C₂₄H₂₁BrFN₅O₂.
Ripretinib API should be packaged in suitable pharmaceutical-grade, tightly closed containers designed to protect the material from contamination and inappropriate environmental exposure.
API storage conditions should be based on the manufacturer's validated stability studies and approved drug-substance specification. The finished Qinlock product has specific storage requirements, but these should not automatically be assigned to bulk Ripretinib API because drug-product and drug-substance stability requirements can differ.
Appropriate documentation for pharmaceutical-grade Ripretinib API may include:
A quality-focused Ripretinib API manufacturer in India should maintain controlled synthetic processes, robust impurity management, validated analytical procedures and consistent batch-release controls.
For oncology APIs such as Ripretinib, particular attention should be given to chemical identity, assay, related substances, potentially mutagenic impurities, residual solvents and solid-state characteristics. Appropriate documentation and traceability are also essential for supporting pharmaceutical formulation development and commercial manufacturing.
| 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 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |