Niraparib is an orally active poly(ADP-ribose) polymerase (PARP) inhibitor used as an antineoplastic pharmaceutical active ingredient. It selectively inhibits PARP-1 and PARP-2 enzymes, which are involved in DNA damage repair. Inhibition of these enzymes can increase DNA damage and contribute to cancer-cell death, particularly in tumors with impaired homologous recombination repair mechanisms.
The commercially used pharmaceutical form is niraparib tosylate monohydrate, the 1:1 salt of niraparib with p-toluenesulfonic acid and one molecule of water. FDA identifies the molecular weight of this form as 510.61 g/mol.
Niraparib is a specialized oncology pharmaceutical API used in the development and manufacture of PARP inhibitor formulations.
Important quality attributes for Niraparib API include identity, assay, related substances, residual solvents, water content, solid-state properties and stereochemical purity. Because Niraparib contains one defined stereocenter, control of the S-enantiomer configuration is an important molecular characteristic. PubChem identifies the active moiety as the S-configured compound.
CAS Number (Niraparib): 1038915-60-4
CAS Number (Niraparib Tosylate): 1038915-73-9
Molecular Formula — Niraparib: C₁₉H₂₀N₄O
Molecular Weight — Niraparib: 320.40 g/mol
Molecular Formula — Niraparib Tosylate Monohydrate: C₂₆H₃₀N₄O₅S
Molecular Weight — Niraparib Tosylate Monohydrate: 510.61 g/mol
Chemical Name: 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide
Drug Class: PARP Inhibitor
Therapeutic Class: Antineoplastic Agent
Therapeutic Area: Oncology
Molecule Type: Synthetic Small Molecule
Salt Form: Tosylate Monohydrate
Development Code: MK-4827
PubChem reports Niraparib CAS 1038915-60-4, molecular formula C₁₉H₂₀N₄O and molecular weight 320.4 g/mol. FDA identifies the marketed tosylate monohydrate as C₂₆H₃₀N₄O₅S with molecular weight 510.61 g/mol.
Niraparib inhibits PARP-1 and PARP-2, enzymes involved in repairing single-strand DNA damage.
Its pharmacological activity includes:
Niraparib is reported as a potent inhibitor of PARP-1 and PARP-2.
Niraparib API is relevant to:
Niraparib is used in pharmaceutical formulations for specific ovarian, fallopian tube and primary peritoneal cancer settings and has also been incorporated into combination therapy for selected prostate cancer patients depending on the approved indication and regulatory jurisdiction. Current prescribing information should be consulted for the applicable indication.
Poly(ADP-ribose) polymerases are important enzymes involved in cellular responses to DNA damage.
Niraparib inhibits PARP activity and interferes with DNA repair. This mechanism is particularly relevant in cancer cells that already have defects in other DNA-repair pathways.
Niraparib tosylate monohydrate is described as a white to off-white, non-hygroscopic crystalline solid in FDA labeling.
The free-base Niraparib has a molecular weight of 320.40 g/mol, while the pharmaceutical tosylate monohydrate has a molecular weight of 510.61 g/mol.
FDA labeling reports that Niraparib has pH-independent solubility below its pKa of 9.95, with aqueous free-base solubility of approximately 0.7–1.1 mg/mL across the physiological pH range.
For CMS purposes, this should be identified as a reported aqueous solubility value for Niraparib/free base, rather than incorrectly presenting it as a universal release specification for Niraparib tosylate monohydrate.
A controlled Niraparib API manufacturing process may involve:
Typical Niraparib API quality-control testing may include:
Store Niraparib API in a tightly closed container under controlled pharmaceutical storage conditions, protected from excessive moisture, heat and direct light.
Storage conditions should ultimately follow the validated stability data and approved API specification.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |