Radotinib is a second-generation tyrosine kinase inhibitor developed for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). It inhibits the BCR-ABL1 fusion kinase and also shows activity against platelet-derived growth factor receptors (PDGFR). Radotinib was approved in South Korea in 2012 under the trade name Supect.
The pharmaceutical product uses the hydrochloride salt, specifically radotinib dihydrochloride. FDA GSRS/NCATS and PubChem identify this substance as CAS 926037-85-6, with molecular formula C₂₇H₂₃Cl₂F₃N₈O and molecular weight 603.43 g/mol.
Radotinib, also known as IY-5511 or IY5511, is an orally active BCR-ABL tyrosine kinase inhibitor. The active moiety has CAS 926037-48-1, molecular formula C₂₇H₂₁F₃N₈O, and molecular weight 530.52 g/mol.
The marketed formulation contains the hydrochloride salt. IUPHAR specifically identifies the marketed formulation as the hydrochloride salt and notes its approval for CML in South Korea.
| Parameter | Details |
|---|---|
| Product Name | Radotinib |
| Pharmaceutical Form | Radotinib Dihydrochloride |
| Primary API CAS | 926037-85-6 |
| Active Moiety CAS | 926037-48-1 |
| API Formula | C₂₇H₂₃Cl₂F₃N₈O |
| API Molecular Weight | 603.43 g/mol |
| Active Moiety Formula | C₂₇H₂₁F₃N₈O |
| Active Moiety MW | 530.52 g/mol |
| FDA UNII – Salt | EF516G9REZ |
| FDA UNII – Active Moiety | I284LJY110 |
| Chemical Class | Synthetic organic small molecule |
| Pharmacological Class | BCR-ABL tyrosine kinase inhibitor |
| Additional Target | PDGFR |
| Therapeutic Area | Oncology / Hematology |
| Main Application | Philadelphia chromosome-positive CML |
| Stereochemistry | Achiral |
NCATS confirms that radotinib is achiral, with zero defined stereocenters, while PubChem confirms the dihydrochloride molecular composition.
Radotinib is primarily associated with targeted treatment of Philadelphia chromosome-positive chronic myeloid leukemia. Its pharmacological activity results from inhibition of BCR-ABL1 signaling, a key driver of Ph+ leukemia. It also inhibits PDGFR signaling.
Pharmaceutical-development applications include:
Radotinib can be characterized using HPLC, LC-MS, NMR and IR. Published analytical work confirms the use of HPLC for radotinib purity determination, while a certificate-of-analysis-based research publication reported radotinib with ≥99% HPLC purity and described it as a pale-yellow crystalline powder.
A current commercial radotinib dihydrochloride reference batch reports:
However, because radotinib is achiral, the reported "ee" value should not be treated as a meaningful universal pharmaceutical release criterion. The commercial batch documentation also includes RP-HPLC, NP-HPLC, LC-MS, MS, IR, NMR and elemental-analysis reports.
Radotinib API manufacturing requires controlled synthesis, purification and hydrochloride salt formation. The manufacturing process should maintain consistent chemical identity, assay, related-substance profile and salt composition.
Important quality controls include:
Radotinib hydrochloride is light-sensitive. Published analytical work describes radotinib hydrochloride as a yellow crystalline powder and states that it was stored in a tight, light-resistant container under refrigerated conditions.
For pharmaceutical API storage, the final temperature and shelf-life should be based on validated stability data.
Typical Radotinib API documentation may include:
A reliable Radotinib API manufacturing program should provide controlled synthesis, reproducible hydrochloride salt formation, validated analytical testing and complete batch documentation. Particular attention should be given to light protection and salt-form consistency because the marketed pharmaceutical form is the hydrochloride salt.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 98.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.2% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |