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PF-06700841 P-Tosylate

CAS No. : 2140301-96-6

MCE 站：PF-06700841 P-Tosylate

产品活性：PF-06700841 P-Tosylate 是一种有效的 JAK1 和 TYK2 双重抑制剂， IC₅₀ 值分别为 17 nM 和 23 nM。PF-06700841 P-Tosylate 还分别以 IC₅₀ 值为 77 nM 和 6.49 μM 抑制 JAK2 和 JAK3。

研究领域：Epigenetics  |  Stem Cell/Wnt  |  JAK/STAT Signaling

作用靶点：JAK

In Vitro: PF-06700841 (Compound 23) potently inhibits TYK2/JAK2 mediated IL-12/pSTAT4 and IL-23/pSTAT3 (human whole blood (HWB) IC₅₀s of 65 and 120 nM, respectively). PF-06700841 has good potency against IL6/pStat1 in the CD3⁺ cellular subset (IC₅₀ of 81 nM), but lower inhibition of IL6/pSTAT3, again in the CD3⁺ cellular subset (IC₅₀ of 641 nM). PF-06700841 also inhibits the JAK1/JAK3 driven γ-common chain cytokines, represented by IL-15/pStat5 and IL-21/pSTAT3 with reasonable potency (HWB IC₅₀s of 238 and 204 nM, respectively). PF-06700841 inhibits EPO/pSTAT5 (JAK2 homodimer) in HWB spiked with CD34⁺ progenitor cells (IC₅₀ of 577 nM). IL10/pSTAT3 (TYK2/JAK1) and IL27/pSTAT3 (JAK1/JAK2/TYK2) are also inhibited by PF-06700841 with IC₅₀s of 305 nM and 86 nM, respectively.

In Vivo: PF-06700841 (Compound 23; 3-30 mg/kg; oral administration; for 7 consecutive days; female Lewis rats) treatment significantly reduces paw volume increase in a dose-dependent manner. The plasma concentrations in animals dosed with PF-06700841 at peak (30 min) and trough (24 h) time intervals post final dose respectively are as follows: 3 mg/kg, 3.54 μM, 0.0221 μM; 10 mg/kg, 10.95 μM, 0.06 μM; and 30 mg/kg, 23.89 μM, 0.06 μM.

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