| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
Ritlecitinib (PF-06651600; Litfulo) is a novel, potent, selective and irreversible/covalent JAK3 inhibitor with the potential to treat autoimmune diseases such as arthritis and Alopecia areata. As of September 2022, FDA has accepted for filing by Pfizer Inc the New Drug Application (NDA) for ritlecitinib to treat alopecia areata. The European Medicines Agency (EMA) has also accepted the Marketing Authorization Application (MAA) for ritlecitinib in the same patient population. It inhibits JAKs with IC50 value of 33.1 nM, and does not have activity (IC50 > 10000 nM) against JAK1, JAK2, and TYK2. PF-06651600 has excellent pharmacokinetics/pharmacodynamics with low clearance, benign toxicity profile and high in vivo efficacy. As a result, PF-06651600 has been in several human clinical studies. In vivo, PF-06651600 reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse autoimmune encephalomyelitis models. Ritlecitinib (Litfulo) was approved in 2023 by FDA for treating Alopecia areata.
| ln Vitro |
Ritlecitinib is a powerful JAK3-selective inhibitor that has an IC50 of 33.1 nM for inhibiting JAK3 kinase activity, but no activity (IC50>10,000 nM) against JAK1, JAK2, and TYK2. With IC50 values of 244, 340, 407, and 266 nM, respectively, ritlecitinib suppresses the phosphorylation of STAT5 induced by IL-2, IL-4, IL-7, and IL-15. With an IC50 of 355 nM, ritlecitinib also prevents IL-21-induced STAT3 phosphorylation. Ritlecitinib inhibits Th1 and Th17 differentiation (measured by IFNγ after 5 days under Th1 circumstances and IL-17 production after 6 days under Th17 settings) in T-cell differentiation assays, according to functional assessment (IC50 values: 30 nM and 167 nM, respectively). Additionally, ritlecitinib inhibits Th1 and Th17 function as demonstrated by the suppression of IFNγ production (IC50=48 nM) and IL-17 production (IC50=269 nM) in cells that have undergone prior differentiation and resting before PF-06651600 treatment[1].
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| ln Vivo |
Ritlecitinib reduces paw swelling in the rat adjuvant-induced arthritis (AIA) model, with an unbound EC50 of 169 nM. In the experimental autoimmune encephalomyelitis (EAE) mouse model, ritlecitinib, administered either therapeutically at 30 or 100 mg/kg or prophylactically at 20 or 60 mg/kg, significantly reduces the severity of the disease. Ritlecitinib's effectiveness in treating inflammatory and autoimmune diseases in these two rodent models shows that JAK3-selective inhibition alone may be enough to modify disease in humans[1].
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| References |
[1]. Telliez JB, et al. Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition. ACS Chem Biol. 2016 Dec 16;11(12):3442-3451
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| Molecular Formula |
C15H19N5O
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| Molecular Weight |
285.34
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| CAS # |
1792180-81-4
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| Related CAS # |
(2R,5S)-Ritlecitinib;1792180-79-0
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| SMILES |
C=CC(N1[C@@H](C)CC[C@@H](NC2=C3C(NC=C3)=NC=N2)C1)=O
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| Chemical Name |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 6.67 mg/mL (23.38 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5046 mL | 17.5230 mL | 35.0459 mL | |
| 5 mM | 0.7009 mL | 3.5046 mL | 7.0092 mL | |
| 10 mM | 0.3505 mL | 1.7523 mL | 3.5046 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.
ACS Chem Biol.2016 Dec 16;11(12):3442-3451. |
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