I am conducting an experiment involving the intramuscular administration of KIN1408 dissolved in SBE-β-CD to 20 g female BALB/c mice. The doses being tested are 2 µg, 5 µg, 10 µg, 15 µg, and 20 µg, with the aim of activating the animals' innate immune response and stimulating the expression of interferons (IFNs). Each mouse will receive a dosing volume of 50 µL.
Could anyone provide insights or recommendations regarding this dosing strategy? Are there specific considerations I should keep in mind when preparing the solution or administering these doses? Your expertise would be greatly appreciated!
KIN1408 is a small-molecule agonist of the RIG-I–like receptor pathway that activates IRF3 and induces innate immune gene expression (e.g., MDA5, RIG-I, IFIT1), so your interferon-focused readouts are well aligned with its known MOA. At a fixed intramuscular (IM) volume of 50 µL, your 2–20 µg dose range translates to ~0.04–0.4 mg/mL in the syringe—concentrations that are typically easy to solubilize in modest SBE-β-CD. A 50 µL IM dose per site is within widely accepted mouse guidelines; if reactogenicity is a concern, you can split higher doses across two sites on opposite hindlimbs.
For formulation, a practical approach is to make KIN1408 in 10–15% (w/v) SBE-β-CD (Captisol®) in sterile saline or PBS, adjust pH to ~7.0–7.4, verify osmolality is near isotonic, then 0.22 µm filter-sterilize. SBE-β-CD is a parenteral-grade solubilizer with good in-vivo tolerability; even IV toxicology packages have used ~12% (w/v) vehicles, so your IM use at similar or lower levels is reasonable. Before dosing, confirm no precipitation after a 1:10 dilution in buffered saline (to mimic interstitial fluid), and keep endotoxin as low as possible. Always include a vehicle-only SBE-β-CD control to rule out any excipient-related innate activation or local irritation.
On administration and PD, inject into the mid-quadriceps with small-gauge needles and alternate legs across timepoints; monitor for local swelling or gait changes. For capturing the interferon window, a time-course at ~2, 6, 12, and 24 h post-dose works well: quantify serum IFN-β and ISG transcripts in muscle at the injection site and draining lymph node. KIN1408 has been shown to drive IRF3 activation and ISG upregulation in human cell models, so you should see early transcriptional changes even if circulating IFN peaks are brief. Keep the per-site volume ≤50 µL and limit the number of IM sites per day to reduce tissue trauma.
The maximum working concentration required is 400 µg/mL. KIN1408 should be dissolved in DMSO at a concentration of 20 mg/mL, followed by dilution using a solution containing 2% DMSO + 98% (20% SBE-β-CD in saline) to achieve clear dissolution. The answer to this question is provided by MedChemExpress Technical Support.
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