Delgocitinib

Storage temp: -20°C

Solubility: DMSO: 58.0 (maximum concentration mg/mL); 186.89 (maximum concentration mM)

Form: Solid

Color: White to Off-white

1. Cell Experiment

DMSO : ≥ 58 mg/mL (186.89 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

"≥" means soluble, but saturation unknown.

Preparing Stock Solutions：

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

2. Animal Experiment

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:

To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.

The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 5% DMSO, 40% PEG300, 5% Tween-80, 50% Saline

Solubility: ≥ 2.5 mg/mL (8.06 mM); Clear solution

Protocol 2

Add each solvent one by one: 5% DMSO, 95% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (8.06 mM); Clear solution

Protocol 3

Add each solvent one by one: 1% DMSO, 99% Saline

Solubility: ≥ 0.5 mg/mL (1.61 mM); Clear solution

Delgocitinib works to attenuate inflammation in inflammatory skin conditions by blocking the molecular signalling of inflammatory mediators. In mice models of atopic dermatitis, delgocitinib improved skin barrier function and enhanced enhanced keratinocyte terminal diferentiation. In human clinical trials, delgocitinib improved the clinical signs and symptoms of chronic hand eczema and atopic dermatitis.

Delgocitinib is a pan Janus kinase (JAK) inhibitor that targets the activity of all four members of the JAK family [JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2)] in a concentration-dependent manner. JAK family has been implicated in several inflammatory disorders, as they mediate the signalling of inflammatory cytokines. In human cells, inhibition of the JAK-STAT pathway by delgocitinib attenuates the signalling of several pro-inflammatory cytokines (including interleukin (IL)-2, IL-4, IL-6, IL-13, IL-21, IL-23, Granulocyte-Macrophage-Colony-Stimulating Factor (GM-CSF), and Interferon (IFN)-α) downregulating the immune and inflammatory responses in cells of relevance to CHE pathology. Delgocitinib blocks the activation of inflammatory cells, such as T cells, B cells, monocytes and mast cells, and the production of cytokines.