Vimseltinib is a synthetic small-molecule kinase inhibitor used as an active pharmaceutical ingredient in oncology pharmaceutical formulations. It is a highly selective inhibitor of the colony-stimulating factor 1 receptor (CSF1R) and is primarily associated with the treatment of tenosynovial giant cell tumor (TGCT) in adults for whom surgical resection is not appropriate.
Vimseltinib is also known by the development code DCC-3014. The active pharmaceutical ingredient used in the marketed pharmaceutical product is vimseltinib dihydrate. Vimseltinib has the molecular formula C23H25N7O2 and a molecular weight of approximately 431.49 g/mol for the anhydrous compound. The dihydrate form has the molecular formula C23H29N7O4 and a molecular weight of approximately 467.52 g/mol.
Vimseltinib is a targeted oncology API that works by selectively inhibiting CSF1R signaling. CSF1R is a receptor tyrosine kinase involved in the proliferation, differentiation and survival of cells of the monocyte-macrophage lineage. Abnormal CSF1R signaling contributes to the accumulation of macrophage-lineage cells in TGCT. By inhibiting this pathway, vimseltinib can reduce CSF1R-mediated cellular activity.
Vimseltinib is a synthetic, non-chiral small molecule. It is generally described as a white to off-white crystalline solid. The drug substance is supplied in the dihydrate form, making control of its solid-state characteristics and water content important during pharmaceutical manufacturing.
The API has significant pH-dependent solubility. Its solubility is substantially higher under acidic conditions and decreases as pH increases. This characteristic is important during formulation development, dissolution testing and pharmaceutical process development.
Vimseltinib is primarily developed for oral pharmaceutical formulations. Its physicochemical properties, crystalline form, particle size and impurity profile are important quality attributes for the finished pharmaceutical product.
Vimseltinib is primarily used in oncology pharmaceutical development and is associated with the treatment of tenosynovial giant cell tumor.
Its pharmaceutical applications include:
Vimseltinib selectively inhibits the colony-stimulating factor 1 receptor (CSF1R), a receptor tyrosine kinase that plays an important role in macrophage biology.
In TGCT, increased CSF1 signaling can contribute to the recruitment and proliferation of macrophage-lineage cells within affected tissues. Vimseltinib inhibits CSF1R signaling and reduces the activity of these cells, providing the basis for its therapeutic effect.
Vimseltinib is a crystalline pharmaceutical substance supplied as a dihydrate. The compound is achiral and does not require control of a single enantiomer.
The drug substance demonstrates strongly pH-dependent aqueous solubility. Regulatory information reports substantially higher solubility under acidic conditions and very low solubility near neutral pH.
The dihydrate form is important for pharmaceutical development because water content and solid-state form can influence the physical properties and stability of the API.
Vimseltinib is manufactured in a controlled crystalline form. Solid-state characterization is an important part of API quality control.
X-ray powder diffraction (XRPD) can be used to confirm the required solid form. Control of the crystalline form helps maintain consistency in:
Vimseltinib API can be evaluated using a range of pharmaceutical analytical techniques, including:
These analytical procedures help establish the identity, purity, physical characteristics and quality of the drug substance.
Impurity control is an important quality attribute for Vimseltinib API.
Public regulatory information identifies several specified impurities and controls them individually. The available regulatory assessment reports NMT 0.15% for each of the specified impurities and NMT 0.10% for an unspecified impurity. The total impurity limit is reported as NMT 1.3%.
Residual solvents are also controlled. Isopropylamine is specifically controlled at NMT 120 ppm in the publicly available regulatory information.
Particle-size distribution is an important quality characteristic of Vimseltinib API. Particle-size testing can be performed using laser diffraction.
Particle-size control can influence the dissolution, processing and formulation performance of a poorly soluble compound. Therefore, particle-size specifications may be incorporated into the approved drug-substance specification.
Vimseltinib demonstrates strongly pH-dependent solubility.
Reported aqueous solubility values at 37°C include approximately:
This pH-dependent behavior is an important consideration in formulation and pharmaceutical development.
Vimseltinib API intended for pharmaceutical manufacturing requires appropriate control of identity, assay, related substances, residual solvents, water content, elemental impurities, crystalline form and particle-size distribution.
The manufacturing process should maintain consistent crystalline form and appropriate impurity control throughout synthesis, crystallization, drying and packaging.
Vimseltinib should be stored in appropriately sealed pharmaceutical-grade packaging under controlled storage conditions. Protection from excessive moisture and unsuitable environmental conditions is recommended.
The actual storage temperature, packaging configuration, retest period and stability requirements should follow the approved API specification and validated stability data.
Vimseltinib API is suitable for pharmaceutical companies involved in oncology drug development, targeted kinase inhibitor formulations and specialty pharmaceutical manufacturing.
Swapnroop Drugs & Pharmaceuticals provides Vimseltinib API for pharmaceutical development, formulation and bulk API requirements, subject to applicable quality and regulatory specifications.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |