Pralsetinib API is a selective receptor tyrosine kinase inhibitor developed to target RET (rearranged during transfection) alterations. Pralsetinib is chemically identified as a cis-configured small molecule with the molecular formula C27H32FN9O2 and molecular weight 533.61 g/mol for the anhydrous active moiety. Its primary CAS Registry Number is 2097132-94-8.
The pharmaceutical active substance used in the approved product is pralsetinib monohydrate, a hydrate form of pralsetinib. FDA GSRS identifies the monohydrate as C27H32FN9O2·H2O, molecular weight 551.62 g/mol, CAS 2548068-68-2. EMA's assessment report states that the selected active substance is pralsetinib monohydrate Form C, with consistent manufacture of this form demonstrated across 18 batches.
Pralsetinib, also known by the development code BLU-667, is an orally active RET tyrosine kinase inhibitor. FDA identifies pralsetinib as the active ingredient of GAVRETO, with a molecular formula of C27H32FN9O2 and molecular weight of 533.61 g/mol.
| Parameter | Value |
|---|---|
| Product Name | Pralsetinib |
| Active Moiety CAS | 2097132-94-8 |
| Commercial API Form | Pralsetinib Monohydrate, Form C |
| Monohydrate CAS | 2548068-68-2 |
| Molecular Formula | C27H32FN9O2 |
| Monohydrate Formula | C27H32FN9O2·H2O |
| Molecular Weight | 533.61 g/mol |
| Monohydrate Molecular Weight | 551.62 g/mol |
| FDA UNII | 1WPE73O1WV |
| Monohydrate UNII | B74S7PPC5G |
| Development Code | BLU-667 |
| Drug Class | RET Tyrosine Kinase Inhibitor |
Pralsetinib is a structurally defined small-molecule kinase inhibitor containing fluorine, nitrogen-rich heterocyclic groups and a substituted cyclohexane carboxamide structure. FDA's chemical substance record confirms three defined stereocenters for pralsetinib and identifies its absolute stereochemistry.
The commercial active substance exists in multiple solid forms. EMA reports that Form C, pralsetinib monohydrate, was selected for the commercial active substance and that the manufacturing process consistently produces this form.
Patent solid-state characterization identifies Form C as a hydrate. Its DSC profile shows thermal events with onsets at approximately 122°C, 127°C and 206°C, while TGA shows approximately 3 wt.% mass loss, consistent with the hydrated form.
Pralsetinib exhibits strongly pH-dependent aqueous solubility. FDA data show solubility decreasing from 0.880 mg/mL at pH 1.99 to less than 0.001 mg/mL at pH 7.64.
Pralsetinib is a targeted anticancer API used as a RET-directed therapy. FDA labeling identifies indications involving RET fusion-positive metastatic non-small cell lung cancer and advanced or metastatic RET fusion-positive thyroid cancer in specified patient populations.
Its pharmacological activity is associated primarily with inhibition of RET signaling. Pralsetinib is therefore particularly relevant to precision oncology applications involving tumors with activating RET alterations.
Pralsetinib requires a more sophisticated API control strategy than a conventional generic small molecule because stereochemistry, solid form, related substances, residual solvents and hydrate state are important quality attributes.
The EMA assessment report states that the active-substance specification includes:
A published HPLC method specifically developed for pralsetinib related substances demonstrated separation of identified impurities and reported impurity levels from three bulk-drug batches. The reported total related substances in those research batches were 0.38%, 0.49% and 0.42%, respectively. These are observed batch results, not official release limits, so they should not be entered as a CMS specification.
A commercial analytical source reports ≥98.0% HPLC purity, while another research-material source reports >99% chemical and optical purity by achiral and chiral HPLC. These should be regarded as commercial/research specifications rather than a universal pharmacopoeial assay limit.
Pralsetinib API manufacturing requires control of chemical purity, stereochemical purity, residual solvents, elemental impurities and crystalline solid form. For the commercially established active substance, maintaining the required pralsetinib monohydrate Form C is particularly important.
Manufacturing and analytical controls should therefore include validated HPLC and chiral-HPLC methods, solid-state characterization by PXRD, water determination by Karl Fischer, residual-solvent testing and appropriate impurity profiling.
Pralsetinib API should be packaged in suitable tightly closed containers that protect the material from moisture and contamination. The commercial active substance is a defined hydrate form, so control of water content and solid form is important during storage and handling.
Storage conditions should be based on validated stability data and the specific batch specification rather than using an unsupported generic temperature claim.
Pralsetinib API documentation can include:
Pralsetinib is a well-characterized targeted oncology API with a defined molecular structure and regulatory characterization. The FDA and EMA records provide detailed information concerning its identity, stereochemistry, active-substance manufacturing and solid-state form. The commercially established active substance is pralsetinib monohydrate Form C, making solid-form control an important part of API quality.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Melting Point | 206°C onset — Form C DSC thermal event |