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Ritlecitinib (PF-06651600)

Cat. No. M6308
Ritlecitinib (PF-06651600) Structure
Synonym:

Ritlecitinib

Size Price Availability Quantity
10mg USD 126  USD140 In stock
25mg USD 279  USD310 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

In vitro: Ritlecitinib (PF-06651600), a newly discovered potent JAK3-selective inhibitor, is highly efficacious at inhibiting γc cytokine signaling, which is dependent on both JAK1 and JAK3. In vitro, it inhibits Th1 and Th17 cell differentiation and function. In total lymphocytes in human whole blood, PF-06651600 inhibits the phosphorylation of STAT5 elicited by IL-2, IL-4, IL-7, and IL-15 with IC50 values of 244, 340, 407, and 266 nM, respectively, and it inhibits the phosphorylation of STAT3 elicited by IL-21 with an IC50 of 355 nM.

In vivo: In vivo, Ritlecitinib (PF-06651600) reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models. PF-06651600 has suitable pharmacokinetics and pharmacodynamics properties for preclinical and clinical evaluations. Human pharmacokinetics of PF-06651600 are predicted to show approximate values of blood clearance of 5.6 mL/min/kg, a steady state volume of distribution of 1.3 L/kg, oral bioavailability of 90%, and a systemic half-life of 2 h.

Protocol
Cell Experiment
Cell lines Th1 and Th17 cells
Preparation method T-cell differentiation in Th1 or Th17 is dependent on cytokines some of which being JAK3-dependent like IL-2 for Th1 cells and IL-21 for Th17 cells, and some being JAK3-independent such as IL-6 and IL-23 for Th17 cells. We therefore assessed the effect of JAK3-versus JAK1-selective inhibition on T helper differentiation. Functional assessment in T-cell differentiation assays demonstrated that PF-06651600 suppressed Th1 and Th17 differentiation as measured by IFNγ, after 5 days under Th1 conditions, and IL-17 production, after 6 days under Th17 conditions, with IC50 values of 30 nM and 167 nM, respectively (Figures 2A and B). PF-06651600 also suppressed Th1 and Th17 function as measured by the inhibition of IFNγ production (IC50 = 48 nM) (Figure 2C) and IL-17 production (IC50 = 269 nM) (Figure 2D) in cells that had been previously differentiated, and rested before being treated with PF-06651600.
Concentrations -
Incubation time 2 days
Animal Experiment
Animal models female Lewis rats (8 to 10 weeks old)
Formulation 2% Tween 80 /0.5% methylcellulose/deionized water
Dosages 80, 15, or 6 mg/kg
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 285.34
Formula C15H19N5O
CAS Number 1792180-81-4
Purity >99%
Solubility DMSO ≥ 60 mg/mL
Storage at -20°C
References

Jak3 deficiency blocks innate lymphoid cell development.
Robinette ML, et al. Mucosal Immunol. 2018 Jan;11(1):50-60. PMID: 28513593.

Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition.
Telliez JB, et al. ACS Chem Biol. 2016 Dec 16;11(12):3442-3451. PMID: 27791347.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: Ritlecitinib (PF-06651600), Ritlecitinib supplier, JAK, inhibitors

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