Vimseltinib

Boiling point: 609.2±65.0°C

Density: 1.29±0.1 g/cm3

Solubility: DMF: 10 mg/mL; DMSO: 10 mg/mL; Ethanol: 10 mg/mL

Form: Solid

Color: Off-white to Light Yellow

1. Cell Experiment

DMSO : 50 mg/mL (115.88 mM; ultrasonic and warming and heat to 60°C)

Preparing Stock Solutions：

Please select an appropriate solvent for the preparation of stock solutions based on the solubility of the product in different solvents. Once prepared, the solution should be aliquoted and stored to avoid product failure caused by repeated freeze-thaw cycles. Storage methods and duration for stock solutions: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, use within 6 months; when stored at -20°C, use within 1 month.

2. Animal Experiment

Please select an appropriate dissolution protocol based on your experimental animals and route of administration. For the following protocols, first prepare a clear stock solution following the in vitro method, then add cosolvents sequentially:

To ensure experimental reliability, the clear stock solution can be appropriately stored according to storage conditions. For in vivo working solutions, it is recommended to prepare them fresh and use on the same day. The percentage indicated before each solvent represents its volume ratio in the final solution. If precipitation occurs during preparation, heating and/or ultrasonication can be used to aid dissolution.

Protocol 1

Add solvents in order: 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% saline

Solubility: ≥ 3.5 mg/mL (8.11 mM); Clear solution

This protocol yields a clear solution of ≥ 3.5 mg/mL (8.11 mM, saturation unknown).

Example for 1 mL working solution: Add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well. Add 50 μL Tween-80 to the mixture and mix thoroughly. Then add 450 μL saline to bring the volume to 1 mL.

Protocol 2

Add solvents in order: 10% DMSO → 90% (20% SBE-β-CD in saline)

Solubility: ≥ 3.5 mg/mL (8.11 mM); Clear solution

This protocol yields a clear solution of ≥ 3.5 mg/mL (8.11 mM, saturation unknown).

Example for 1 mL working solution: Add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix well.

Protocol 3

Add solvents in order: 10% DMSO → 90% corn oil

Solubility: ≥ 3.5 mg/mL (8.11 mM); Clear solution

This protocol yields a clear solution of ≥ 3.5 mg/mL (8.11 mM, saturation unknown). This method is not suitable for experiments lasting longer than half a month.

Example for 1 mL working solution: Add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well.

Higher vimseltinib exposure is associated with an increased risk of adverse effects, including edema, rash, and increased liver enzymes. The exposure-response relationship for efficacy and time course of pharmacodynamic response have not been fully characterized.

Cases of severe liver toxicity have been observed in patients undergoing treatment with another CSF1R inhibitor, pexidartinib. This effect has not been observed in patients receiving vimseltinib, but patient liver function should be monitored regularly per prescribing information regardless.

Vimseltinib is a kinase inhibitor targeting colony-stimulating factor 1 receptor (CSF1R), a type III receptor tyrosine kinase which is crucial for survival, proliferation, and differentiation of myeloid lineage cells such as macrophages, microglial cells and osteoclasts. Abnormal CSF1R signaling has been observed in several diseases including cancer, arthritis, inflammatory disorders, Alzheimer’s Disease, and Parkinson’s Disease. Vimseltinib specifically acts by stabilizing CSF1R in its inactive state by exploiting its switch-control region, thereby inhibiting autophosphorylation, downstream signaling induced by CSF1 ligand binding, and proliferation of cells expressing CSF1R.