Pemigatinib is a selective small-molecule fibroblast growth factor receptor (FGFR) kinase inhibitor developed for targeted oncology applications. It primarily inhibits FGFR1, FGFR2, and FGFR3 signaling pathways, which can play an important role in the growth and progression of certain cancers. Pemigatinib API is therefore an important pharmaceutical active ingredient for the development and manufacturing of targeted oral anticancer formulations.
With the chemical name associated with CAS No. 1513857-77-6 and a molecular weight of approximately 487.5 g/mol, pemigatinib is characterized as a synthetic, achiral small molecule. The API is available as a crystalline solid, with Form I recognized as the commercially relevant polymorphic form.
Pemigatinib is used as the active pharmaceutical ingredient in targeted therapies designed for cancers involving specific FGFR alterations. Its mechanism of action makes it particularly relevant to precision oncology, where treatment selection can be based on molecular characteristics of the tumor.
Key pharmaceutical applications include:
Pemigatinib has been associated particularly with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma and certain FGFR1-rearranged myeloid/lymphoid neoplasms.
Pemigatinib works by inhibiting FGFR kinase activity. FGFRs are receptor tyrosine kinases involved in cellular signaling pathways that regulate processes such as cell proliferation, differentiation, survival, and angiogenesis.
Genetic alterations involving FGFR signaling can contribute to abnormal tumor growth. By selectively inhibiting FGFR1–3 activity, pemigatinib can interfere with downstream signaling associated with these pathways.
This targeted mechanism distinguishes pemigatinib from conventional nonspecific cytotoxic anticancer agents and makes it relevant to biomarker-driven treatment strategies.
Pemigatinib is a white to off-white crystalline solid and is described as non-hygroscopic. It is an achiral compound, meaning that conventional stereochemical resolution is not required for the API.
Important characteristics include:
| Property | Details |
|---|---|
| API Name | Pemigatinib |
| CAS Number | 1513857-77-6 |
| Molecular Formula | C24H27F2N5O4 |
| Molecular Weight | 487.5 g/mol |
| Physical Form | White to off-white crystalline solid |
| Solid Form | Form I |
| Chirality | Achiral |
| Hygroscopicity | Non-hygroscopic |
| Therapeutic Area | Oncology |
| Pharmacological Class | FGFR kinase inhibitor |
Polymorphism is an important quality consideration for pharmaceutical APIs because different crystal forms can influence physical properties such as dissolution, stability, processing behavior, and bioavailability.
Pemigatinib has been characterized in crystalline form, with Form I identified as the commercially relevant and thermodynamically stable form. Solid-state characterization can include techniques such as X-ray powder diffraction (XRPD) and other appropriate analytical methods.
For pharmaceutical manufacturing, controlling the intended solid form helps maintain consistency between API batches and supports predictable formulation performance.
Pemigatinib demonstrates strongly pH-dependent aqueous solubility. Its solubility is substantially higher under acidic conditions and decreases as the pH increases.
This behavior is relevant to pharmaceutical formulation and dissolution testing because gastrointestinal pH can influence the apparent solubility of the API. Regulatory characterization has demonstrated markedly reduced solubility under near-neutral conditions.
The pH-dependent behavior should therefore be considered when evaluating:
Quality control is an essential part of pemigatinib API manufacturing. Appropriate analytical testing can be used to confirm identity, assay, purity, impurity profile, solid form, and other critical quality attributes.
Depending on the applicable specification, analytical characterization may include:
The exact numerical acceptance criteria should be established according to the applicable validated API specification rather than applying generic limits.
Pemigatinib API manufacturing requires controlled chemical synthesis followed by purification, isolation, drying, and solid-state control. Each stage should be appropriately monitored to maintain the desired chemical purity and crystalline form.
Critical manufacturing considerations can include:
A controlled manufacturing process helps provide consistent API quality for downstream pharmaceutical formulation.
A comprehensive analytical strategy is particularly important for a kinase-inhibitor API such as pemigatinib. Chromatographic methods can be used for quantitative assay and impurity profiling, while spectroscopic and solid-state techniques provide complementary characterization.
HPLC/UPLC: Used for assay and related-substance evaluation.
Mass Spectrometry: Supports molecular identification and characterization.
XRPD: Used to identify and monitor crystalline Form I.
Water Determination: Can be performed using an appropriate validated method when required by the product specification.
Residual Solvents: Evaluated according to the applicable pharmaceutical quality requirements.
Elemental Impurities: Assessed using appropriate validated analytical procedures and applicable ICH requirements.
Pemigatinib API should be stored under conditions established by the applicable manufacturer specification and stability data. The material should be protected from unsuitable environmental conditions and handled using appropriate pharmaceutical manufacturing procedures.
Recommended handling considerations include:
Pemigatinib is relevant to pharmaceutical companies involved in targeted oncology product development, analytical research, formulation studies, and API manufacturing. Its selective FGFR activity and defined crystalline form make characterization of both chemical purity and solid-state properties important during development.
For formulation scientists, the API's pH-dependent solubility profile is an important consideration when developing dosage forms and evaluating dissolution behavior. For analytical teams, impurity profiling and polymorph characterization are key elements of a comprehensive quality-control program.
The increasing importance of precision medicine has increased the role of molecularly targeted therapies in oncology. Pemigatinib represents a targeted approach based on specific FGFR alterations, making its API relevant to specialized anticancer pharmaceutical development.
Its combination of selective FGFR activity, defined molecular structure, crystalline Form I, and characterized physicochemical properties makes pemigatinib an important API for targeted oncology applications.
What is Pemigatinib API?
Pemigatinib API is a synthetic small-molecule FGFR kinase inhibitor used in the development and manufacture of targeted oncology medicines.
What is the CAS number of Pemigatinib?
The CAS number of pemigatinib is 1513857-77-6.
What is the molecular weight of Pemigatinib?
Pemigatinib has a molecular weight of approximately 487.5 g/mol.
What receptors does Pemigatinib target?
Pemigatinib selectively inhibits FGFR1, FGFR2, and FGFR3.
What is the physical form of Pemigatinib API?
Pemigatinib is characterized as a white to off-white crystalline solid.
Is Pemigatinib hygroscopic?
Pemigatinib has been characterized as non-hygroscopic.
Does Pemigatinib have different polymorphic forms?
Pemigatinib has been characterized in crystalline forms, with Form I identified as the commercially relevant form.
Is Pemigatinib soluble in water?
Pemigatinib has strongly pH-dependent aqueous solubility, with substantially higher solubility under acidic conditions and very low solubility at higher pH.
What is the therapeutic use of Pemigatinib?
Pemigatinib is used in targeted oncology treatment for specific malignancies involving defined FGFR alterations.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| 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 | ≤ 1.5% |
| Water Content | NMT 1.0% |