| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
JAK1 and JAK3 (Janus kinase 1 and Janus kinase 3). Fosifidancitinib is a potent inhibitor of JAK1 and JAK3. As a prodrug, it is likely dephosphorylated in vivo by alkaline phosphatases or other esterases to release the active parent JAK inhibitor. The active agent inhibits JAK1 and JAK3 kinase activity, thereby blocking the phosphorylation and activation of STAT transcription factors downstream of cytokine receptors that utilize the common gamma chain (gammac) (e.g., IL-2, IL-4, IL-7, IL-9, IL-15, IL-21). This inhibits T cell activation, proliferation, and cytokine production, and reduces inflammation in autoimmune and allergic conditions.
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| ln Vitro |
Cell-free biochemical assays for fosifidancitinib are typically performed after activation to the active metabolite, or the compound may be tested directly if it has intrinsic activity. The active parent inhibitor (likely ifidancitinib or a related compound) potently inhibits JAK1 and JAK3 with IC50 values in the low nanomolar range, with minimal activity against JAK2 and TYK2. The prodrug form may have reduced intrinsic activity in cell-free assays compared to the active parent, requiring metabolic activation. Fosifidancitinib inhibits JAK1/3 in cellular assays after uptake and activation. In stimulated immune cells, fosifidancitinib (or its active form) inhibits phosphorylation of STAT proteins and reduces expression of inflammatory cytokines. The compound is used in studies of allergies, asthma, and autoimmune diseases, consistent with the known role of JAK1/3 in these conditions.
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| Enzyme Assay |
Dedicated cell-free assays for fosifidancitinib are not standard unless the compound has intrinsic activity. Typically, the active metabolite is studied. JAK1 and JAK3 inhibition is measured using a HTRF (Homogeneous Time-Resolved Fluorescence) kinase assay format. Recombinant JAK1 or JAK3 enzyme is incubated with a biotinylated peptide substrate (e.g., STAT3-derived peptide), ATP (1-10 uM), and varying concentrations of the active inhibitor (0.001-1000 nM) in assay buffer for 30-60 minutes at room temperature. The reaction is stopped, and phosphorylated peptide is detected using a phospho-specific antibody and HTRF donor/acceptor beads. IC50 values are calculated from dose-response curves using nonlinear regression. Alternatively, the prodrug fosifidancitinib may be tested in the presence of phosphatases to convert it to the active form. For selectivity profiling, the compound is tested against a panel of kinases.
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| Cell Assay |
Cellular assays for JAK1/3 inhibition use PBMCs or specific cell lines. For phospho-STAT (p-STAT) assays, cells are pre-treated with fosifidancitinib (0.1-1000 nM) for 1 hour, then stimulated with IL-2 (10 ng/mL), IL-4 (10 ng/mL), IL-7, or IL-15 for 15-30 minutes. Cells are fixed, permeabilized, and stained with antibodies against p-STAT5 (for JAK3/IL-2) or p-STAT6 (for JAK1/IL-4). p-STAT levels are measured by flow cytometry. The IC50 for inhibition of p-STAT is determined. For T cell proliferation, CFSE-labeled T cells are stimulated with IL-2 or anti-CD3/CD28 antibodies in the presence of fosifidancitinib for 72-96 hours. Proliferation is measured by CFSE dilution by flow cytometry. Cytokine production (e.g., IFNgamma, IL-4, IL-17, IL-2) is measured in cell culture supernatants by ELISA or multiplex assays. For functional assays in B cells, IL-4 stimulation and IgE production can be measured.
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| Animal Protocol |
In vivo studies for fosifidancitinib are not extensively reported in available literature. As a JAK1/3 inhibitor, it is expected to show efficacy in rodent models of allergic asthma, atopic dermatitis, and autoimmune diseases. Typical study designs include: OVA-induced allergic asthma model in mice-fosifidancitinib administered orally (1-30 mg/kg QD) or intraperitoneally for 2-3 weeks, endpoints include airway hyperresponsiveness (methacholine challenge), eosinophil counts in bronchoalveolar lavage fluid, serum IgE levels, and lung histopathology. For atopic dermatitis, repeated topical application of oxazolone or MC903 to mouse skin induces dermatitis; fosifidancitinib is applied topically or given systemically. For alopecia areata, the C3H/HeJ mouse model of spontaneous alopecia can be used with oral or topical administration. For autoimmune arthritis (collagen-induced arthritis model), fosifidancitinib is administered orally for 3-6 weeks, with assessment of paw swelling, clinical scores, and histopathology.
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| ADME/Pharmacokinetics |
Formal PK studies for fosifidancitinib are not fully disclosed. As a phosphate ester prodrug, it is designed to have improved aqueous solubility compared to the parent compound, which may enable higher concentrations in solution formulations for oral or injectable administration. Following administration, fosifidancitinib is expected to be rapidly dephosphorylated by alkaline phosphatases (particularly intestinal alkaline phosphatase) or other esterases to release the active JAK inhibitor. The active parent compound then exhibits typical JAK inhibitor PK: moderate-to-high oral bioavailability, Cmax achieved in 1-3 hours, terminal half-life of 3-8 hours, moderate-to-high plasma protein binding, and metabolism primarily by CYP3A4. The prodrug strategy may improve formulation characteristics but does not fundamentally alter the PK of the active metabolite. Detailed PK parameters for fosifidancitinib itself (e.g., fraction converted, prodrug half-life) have not been published.
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| Toxicity/Toxicokinetics |
Toxicity data for fosifidancitinib are not extensively published. The safety profile is expected to be similar to that of other JAK1/3 inhibitors, including ifidancitinib and related compounds. In preclinical studies, JAK1/3 inhibitors are generally well-tolerated at therapeutic doses. Common adverse events in clinical studies of JAK1/3 inhibitors include upper respiratory tract infections, headache, nausea, and fatigue. Class-related adverse events for JAK inhibitors include increased risk of infections (e.g., herpes zoster), thromboembolic events (particularly with JAK2 inhibition), and potential changes in lipid parameters. Because fosifidancitinib is a prodrug designed to release a selective JAK1/3 inhibitor (avoiding significant JAK2 inhibition), the risk of thrombotic events may be reduced compared to pan-JAK inhibitors. However, formal toxicology studies for fosifidancitinib specifically have not been published.
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| References | |
| Additional Infomation |
Fosifidancitinib is a research-grade prodrug of a JAK1/3 inhibitor, likely ifidancitinib or a close analog. The phosphate group improves solubility and may enable alternative formulation strategies. The molecular formula is C21H21FN5O7P, with molecular weight 505.39. The compound is supplied as a solid (purity >98%) and is soluble in DMSO (but DMSO solubility may be limited; insoluble as noted in some sources). It is stored at -20degC for long-term stability. The CAS number is 1237168-58-9. Fosifidancitinib is intended for research purposes only and is not approved for human therapeutic use. The compound is used in studies of allergies, asthma, autoimmune diseases, and inflammatory conditions. As a phosphate prodrug, it can be used to study the effects of improved solubility and bioavailability of the active JAK1/3 inhibitor. The name "Fosifidancitinib" is the International Nonproprietary Name (INN) for the phosphate prodrug. The compound is also known as V41810. Detailed published literature on fosifidancitinib is limited, and most information is derived from supplier data sheets and brief bioactivity descriptions. Investigators should consult primary literature if available for specific experimental details.
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| Molecular Formula |
C21H21FN5O7P
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|---|---|
| Molecular Weight |
505.3929
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| Exact Mass |
505.116
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| CAS # |
1237168-58-9
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| Related CAS # |
1237168-58-9(free base);1357103-62-8(disodium);
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| PubChem CID |
58071385
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
723.1±70.0 °C at 760 mmHg
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| Flash Point |
391.1±35.7 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.680
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| LogP |
2.15
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
793
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| Defined Atom Stereocenter Count |
0
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| SMILES |
P(=O)(O[H])(O[H])OC([H])([H])N1C(=O)OC2C([H])=C([H])C(=C([H])C1=2)N([H])C1C(C([H])([H])[H])=C([H])N=C(N([H])C2=C([H])C(=C(C(C([H])([H])[H])=C2[H])F)OC([H])([H])[H])N=1
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| InChi Key |
JTUBTEKGIDQZMZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21FN5O7P/c1-11-6-14(8-17(32-3)18(11)22)25-20-23-9-12(2)19(26-20)24-13-4-5-16-15(7-13)27(21(28)34-16)10-33-35(29,30)31/h4-9H,10H2,1-3H3,(H2,29,30,31)(H2,23,24,25,26)
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| Chemical Name |
[5-[[2-(4-fluoro-3-methoxy-5-methylanilino)-5-methylpyrimidin-4-yl]amino]-2-oxo-1,3-benzoxazol-3-yl]methyl dihydrogen phosphate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9787 mL | 9.8933 mL | 19.7867 mL | |
| 5 mM | 0.3957 mL | 1.9787 mL | 3.9573 mL | |
| 10 mM | 0.1979 mL | 0.9893 mL | 1.9787 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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