Ponatinib is a synthetic small-molecule tyrosine kinase inhibitor supplied pharmaceutically as ponatinib hydrochloride. The hydrochloride salt has CAS No. 1114544-31-8, molecular formula C₂₉H₂₈ClF₃N₆O, and molecular weight 569.02 g/mol. The free-base form has CAS No. 943319-70-8 and molecular weight 532.56 g/mol. FDA's original chemistry review confirms these two distinct substance identities.
Ponatinib inhibits multiple tyrosine kinases, including BCR-ABL, and was specifically developed to retain activity against resistant BCR-ABL mutations including T315I. It is the active ingredient in Iclusig.
The pharmaceutical API is ponatinib hydrochloride, the monohydrochloride salt of ponatinib. It is described as an off-white to yellow crystalline, anhydrous solid. A single crystalline form of ponatinib hydrochloride has been identified by XRPD, and DSC reports a melting range of approximately 250–265°C.
Ponatinib hydrochloride is a multi-targeted kinase inhibitor with activity against BCR-ABL and several other tyrosine kinases. FDA labeling reports pKa values of 2.77 and 7.8 and demonstrates strongly pH-dependent aqueous solubility.
| Parameter | Details |
|---|---|
| Product Name | Ponatinib |
| Pharmaceutical API Form | Ponatinib Hydrochloride |
| Synonym | AP24534 Hydrochloride |
| HCl CAS Number | 1114544-31-8 |
| Free Base CAS Number | 943319-70-8 |
| Molecular Formula | C₂₉H₂₈ClF₃N₆O |
| Molecular Weight | 569.02 g/mol |
| Free Base Molecular Weight | 532.56 g/mol |
| Molecular Type | Small-Molecule Tyrosine Kinase Inhibitor |
| FDA UNII – Free Base | 4340891KFS |
| ChEBI | CHEBI:78543 |
| DrugBank | DB08901 |
| Physical Form | Off-white to yellow crystalline solid |
| Solid State | Anhydrous crystalline form |
| pKa | 2.77 and 7.8 |
| Melting / DSC Range | 250–265°C |
| Storage | Protect from moisture; product-specific storage conditions apply |
FDA confirms the HCl molecular formula and molecular weight, while the solid-state and DSC information is reported for ponatinib HCl.
Ponatinib is an antineoplastic tyrosine kinase inhibitor used in the treatment of certain Philadelphia chromosome-positive (Ph+) leukemias, including chronic myeloid leukemia and acute lymphoblastic leukemia. Its development was particularly important for BCR-ABL disease involving the T315I mutation, which confers resistance to many earlier BCR-ABL inhibitors.
Ponatinib inhibits BCR-ABL as well as other kinases including SRC, VEGFR, FGFR and PDGFR families.
Ponatinib hydrochloride is a chemically defined small-molecule API and can be evaluated using conventional pharmaceutical analytical techniques.
Relevant analytical testing can include:
FDA's chemistry review confirms that HPLC methods for ponatinib were evaluated and accepted for quality-control/regulatory purposes.
Commercial analytical/reference materials commonly report ≥98% HPLC purity, while individual research batches can report higher values such as 99.76% or 99.98%. These batch/reference values should not be presented as a universal pharmacopoeial API acceptance criterion.
Ponatinib hydrochloride is a specialized oncology API requiring controlled synthesis, salt formation, purification and solid-state characterization. Appropriate manufacturing controls should address chemical purity, related substances, residual solvents, salt identity, solid-state form and stability.
Technical documentation can include batch-specific analytical data, certificates, specifications, safety documentation and other quality/regulatory information applicable to the API.
Ponatinib hydrochloride should be protected from moisture and stored according to the validated stability conditions of the specific API batch.
Commercial reference materials report storage conditions including 2–8°C or −20°C, depending on the supplier and intended material. Cayman, for example, specifies −20°C for its research material, while other commercial materials specify 4°C or 2–8°C.
For a pharmaceutical API page, it is preferable to state the validated manufacturer stability condition rather than incorrectly presenting a research-reagent storage temperature as a universal pharmaceutical requirement.
Typical documentation may include:
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 3.0% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |
| Melting Point | 250–265°C |