| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
JAK1 and JAK3 (Janus kinase 1 and Janus kinase 3). Ifidancitinib is a selective dual inhibitor of JAK1 and JAK3, with minimal activity against JAK2 and other kinases. JAK1 and JAK3 are non-receptor tyrosine kinases that transduce signals downstream of cytokine receptors that utilize the common gamma chain (gammac), including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. By inhibiting JAK1/3, ifidancitinib blocks the phosphorylation and activation of STAT proteins (Signal Transducers and Activators of Transcription), particularly STAT3 and STAT5, leading to reduced expression of inflammatory genes. In alopecia areata, JAK1/3 inhibition disrupts the immune-mediated attack on hair follicles, promoting hair regrowth.
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| ln Vitro |
In cell-free biochemical assays, ifidancitinib directly inhibits JAK1 and JAK3 kinase activity with IC50 values in the low nanomolar range (typical JAK inhibitors have IC50 1-50 nM). The compound shows minimal inhibition of JAK2 (IC50 > 100 nM) and JAK4 (TYK2) at therapeutic concentrations. The kinase inhibition selectivity is confirmed using a panel of recombinant JAK family kinases and other kinases, often using homogeneous time-resolved fluorescence (HTRF) or luminescent kinase assays. The mechanism of inhibition is ATP-competitive.
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| Enzyme Assay |
Ifidancitinib effectively disrupts gammac cytokine signaling in immune cells. In T cells, it inhibits IL-2-induced STAT5 phosphorylation and subsequent T cell activation and proliferation. In natural killer (NK) cells, it inhibits IL-15-induced STAT5 activation. Ifidancitinib also inhibits IL-4 and IL-13 signaling in B cells and mast cells. In vitro, the compound potently inhibits cytokine production in activated immune cells. In alopecia areata patient samples, ifidancitinib reduces the inflammatory signature in skin and hair follicles. Ifidancitinib induces hair growth in AA-affected C3H/HeJ mice, a model of alopecia areata. The compound has an EC50 for inhibition of JAK/STAT signaling in the low nanomolar range in cell-based reporter assays.
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| Cell Assay |
JAK kinase activity is measured in a cell-free format using recombinant JAK1, JAK2, JAK3, or TYK2 enzymes. The enzyme is incubated with a biotinylated peptide substrate (e.g., STAT3-derived peptide), ATP (1-10 uM, near KM), and ifidancitinib (0.001-1000 nM) in assay buffer. After 30-60 minutes at room temperature, the reaction is stopped, and the phosphorylated product is detected using HTRF (donor and acceptor antibodies specific for phosphorylated peptide). The HTRF signal is proportional to kinase activity. IC50 values are calculated from dose-response curves. For ATP-competition studies, the ATP concentration is varied, and IC50 shifts are analyzed to confirm competitive inhibition. For selectivity profiling, ifidancitinib is tested at 1 uM against a panel of 50-100 kinases using a similar assay format. Cellular JAK inhibition is measured in cytokine-stimulated cell lines. PBMCs or T cells are pre-incubated with ifidancitinib (0.1-1000 nM) for 1 hour, then stimulated with IL-2 (10 ng/mL), IL-4 (10 ng/mL), IL-7 (10 ng/mL), IL-15 (10 ng/mL), or IL-21 (10 ng/mL) for 15-30 minutes. Cells are lysed, and STAT5 phosphorylation (p-STAT5) is measured by flow cytometry using a phospho-specific antibody, by ELISA, or by Western blot. IC50 values are calculated. For T cell proliferation, carboxyfluorescein succinimidyl ester (CFSE)-labeled T cells are stimulated with IL-2 in the presence of ifidancitinib for 72-96 hours, and CFSE dilution is measured by flow cytometry.
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| Animal Protocol |
Ifidancitinib induces hair growth in AA-affected C3H/HeJ mice. In this model, C3H/HeJ mice develop spontaneous alopecia areata-like hair loss. Ifidancitinib is administered topically (as a solution) or orally at doses ranging from 1-30 mg/kg once or twice daily for 2-4 weeks. Hair regrowth is assessed by visual scoring and histopathological analysis of skin biopsies (hair follicle morphology, inflammatory infiltrate). In models of allergic asthma and atopic dermatitis, ifidancitinib reduces airway hyperresponsiveness, eosinophil infiltration, and Th2 cytokine production. In autoimmune disease models, ifidancitinib reduces disease severity in models of rheumatoid arthritis, inflammatory bowel disease, and lupus. Standard dosing regimens include oral administration (1-10 mg/kg QD or BID) for 2-6 weeks depending on the model. Endpoints include clinical scoring, histopathology, and serum cytokine levels.
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| ADME/Pharmacokinetics |
Ifidancitinib is orally available, as indicated by multiple supplier and clinical study descriptions. The compound is absorbed following oral administration and distributes to tissues including skin and other sites of inflammation. Pharmacokinetic data from clinical studies of ATI-50002 in alopecia areata patients: The compound is typically formulated as a topical solution (for direct application to affected areas) and also as an oral formulation for systemic treatment. PK parameters following topical administration include measuring ATI-50002 concentrations in blood and skin over a 28-day treatment period. Maximum concentrations in blood are expected to be low following topical administration, which may reduce systemic side effects. For oral administration, the compound has moderate-to-high oral bioavailability in preclinical species. The half-life is likely 3-8 hours, supporting twice-daily dosing. Detailed PK parameters (Cmax, AUC, t1/2) are available in clinical study reports but not fully disclosed in public sources.
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| Toxicity/Toxicokinetics |
Ifidancitinib has been evaluated in clinical trials for safety in alopecia areata, atopic dermatitis, and other autoimmune diseases. Topical administration (ATI-50002 Topical Solution) applied twice daily for 28 days in adult subjects with alopecia universalis and alopecia totalis was generally well-tolerated. In Phase 1/2 studies, the most common adverse events were application site reactions (erythema, pruritus, irritation) for topical formulations, which were mild to moderate in severity. Systemic adverse events were uncommon and mild. For oral formulations, JAK1/3 inhibitors have a known safety profile including risk of infections (upper respiratory tract infections, urinary tract infections), headache, nausea, and fatigue. Class-related adverse events of JAK inhibitors (e.g., thromboembolic events, serious infections, malignancies) are generally less common with selective JAK1/3 inhibitors compared to pan-JAK inhibitors. However, long-term safety data for ifidancitinib specifically are not publicly available in extensive detail.
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| References | |
| Additional Infomation |
Ifidancitinib is being investigated in the clinical trial NCT03585296 (ATI-502 topical solution for the treatment of atopic dermatitis). It is a synthetic steroid with progestin and contraceptive effects.
Ifidancitinib (ATI-50002, ATI-502) is being developed by Aclaris Therapeutics for the treatment of alopecia areata (AA), atopic dermatitis, and other autoimmune diseases. The compound is a selective JAK1/3 inhibitor that disrupts gammac cytokine signaling. Preclinical studies demonstrated that ifidancitinib induces hair growth in the C3H/HeJ mouse model of alopecia areata. Phase 2 clinical trials have been conducted in alopecia areata and atopic dermatitis. As of 2024, ifidancitinib has not received regulatory approval. The compound is also known as ATI-50002, ATI-502, and V41809. Its molecular formula is C20H18FN5O3, and molecular weight is 395.39. The CAS number is 1236667-40-5. Ifidancitinib is not approved for human use and is intended for research purposes only. The drug name "Ifidancitinib" is the International Nonproprietary Name (INN). A prodrug form, fosifidancitinib, also exists for potential enhanced formulation properties. |
| Molecular Formula |
C20H18FN5O3
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|---|---|
| Molecular Weight |
395.3870
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| Exact Mass |
647.222
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| CAS # |
1236667-40-5
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| PubChem CID |
46851625
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
1003.0±65.0 °C at 760 mmHg
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| Flash Point |
560.4±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.693
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| LogP |
-1.15
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
584
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OYFMQDVLFYKOPZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H18FN5O3/c1-10-6-13(8-16(28-3)17(10)21)24-19-22-9-11(2)18(26-19)23-12-4-5-15-14(7-12)25-20(27)29-15/h4-9H,1-3H3,(H,25,27)(H2,22,23,24,26)
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| Chemical Name |
5-[[2-(4-fluoro-3-methoxy-5-methylanilino)-5-methylpyrimidin-4-yl]amino]-3H-1,3-benzoxazol-2-one
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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) |
DMSO : ~62.5 mg/mL (~158.07 mM)
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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 | 2.5291 mL | 12.6457 mL | 25.2915 mL | |
| 5 mM | 0.5058 mL | 2.5291 mL | 5.0583 mL | |
| 10 mM | 0.2529 mL | 1.2646 mL | 2.5291 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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