Ribociclib is a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor used as an important targeted anticancer active pharmaceutical ingredient. The pharmaceutical form is commonly handled as ribociclib succinate, the succinate salt of ribociclib. Ribociclib is used in combination with endocrine therapy for hormone receptor (HR)-positive, HER2-negative breast cancer.
The current FDA labeling includes use in adults with HR-positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, as well as adults with HR-positive, HER2-negative advanced or metastatic breast cancer.
Ribociclib Succinate API
PubChem identifies CAS 1374639-75-4 as ribociclib succinate and reports a molecular weight of 552.6 g/mol. The FDA label specifies 552.64 g/mol for ribociclib succinate and 434.55 g/mol for the free base.
Ribociclib succinate is a crystalline salt form of ribociclib. FDA describes the material as a light yellow to yellowish-brown crystalline powder.
The ribociclib molecule contains a pyrrolopyrimidine core with cyclopentyl, piperazine and pyridine structural elements. The succinate salt improves the pharmaceutical handling characteristics of the active moiety.
IUPAC name:
Butanedioic acid; 7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide.
Selected physicochemical descriptors for ribociclib succinate:
| Parameter | Value |
|---|---|
| Molecular Weight | 552.64 g/mol |
| Exact Mass | 552.28086628 Da |
| H-Bond Donors | 4 |
| H-Bond Acceptors | 11 |
| Rotatable Bonds | 8 |
| Topological Polar Surface Area | 166 Ų |
| Defined Stereocenters | 0 |
PubChem reports these calculated molecular descriptors for ribociclib succinate.
Ribociclib API is primarily used in pharmaceutical development and manufacturing of CDK4/6-targeted oncology formulations.
Current FDA-labeled applications include:
For early breast cancer, the FDA-recommended ribociclib dosage is 400 mg once daily for 21 consecutive days followed by 7 days off. For advanced or metastatic breast cancer, the recommended dosage is 600 mg once daily for 21 days followed by 7 days off.
Ribociclib selectively inhibits cyclin-dependent kinases CDK4 and CDK6. These kinases form complexes with D-type cyclins and regulate progression through the cell cycle.
CDK4/6 inhibition reduces phosphorylation of the retinoblastoma protein (pRb). This suppresses progression from the G1 phase toward the S phase of the cell cycle, resulting in reduced cellular proliferation. FDA labeling reports that ribociclib decreased pRb phosphorylation and produced G1-phase cell-cycle arrest in vitro.
In HR-positive breast cancer models, combining ribociclib with endocrine therapy produces greater tumor-growth inhibition than either treatment alone.
Ribociclib succinate API quality control can include:
Important: A universal publicly accessible numerical API release specification for assay, individual impurities, total impurities, water and residual solvents was not verified from an authoritative current pharmacopoeial monograph during this research. These values should therefore be controlled according to the applicable approved API specification rather than invented.
Ribociclib succinate manufacturing involves controlled synthesis of the ribociclib active moiety followed by salt formation with succinic acid and controlled crystallization.
A pharmaceutical-grade manufacturing process should incorporate:
Particular attention should be given to chemical purity, residual solvents, polymorphic form and process-related impurities.
| Property | Ribociclib Succinate |
|---|---|
| Appearance | Light yellow to yellowish-brown crystalline powder |
| Molecular Formula | C₂₃H₃₀N₈O·C₄H₆O₄ |
| Molecular Weight | 552.64 g/mol |
| Free Base MW | 434.55 g/mol |
| CAS Number | 1374639-75-4 |
| Exact Mass | 552.28086628 Da |
| HBD | 4 |
| HBA | 11 |
| Rotatable Bonds | 8 |
| TPSA | 166 Ų |
| Stereocenters | 0 |
The appearance and molecular-weight values are supported by the FDA labeling, while the calculated molecular descriptors are reported by PubChem.
For API supply, packaging should provide suitable protection against moisture, contamination and environmental exposure. The selected packaging configuration should be compatible with the approved stability and handling requirements.
For the finished KISQALI product, the current DailyMed labeling specifies storage at 20–25°C, with excursions permitted between 15–30°C, and recommends keeping tablets in the original blister package to protect them from moisture.
Finished pharmaceutical products should not be used as a substitute for the API manufacturer's validated API storage specification.
Typical pharmaceutical documentation for Ribociclib Succinate API can include:
A qualified Ribociclib Succinate API manufacturer should maintain strong controls over synthetic chemistry, salt formation, crystallization, impurity profiling and analytical characterization. Reliable manufacturing should be supported by validated analytical methods, controlled raw materials, documented batch traceability and appropriate stability programs.
For pharmaceutical companies developing or manufacturing ribociclib-containing formulations, consistent control of assay, related substances, residual solvents, water content, solid-state properties and other critical quality attributes is essential for reproducible API performance.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Residue on Ignition | NMT 0.2% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 2.0 – 4.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.5% |
| Water Content | NMT 1.0% |