Brepocitinib (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。Brepocitinib P-Tosylate 还分别以 IC₅₀ 值为 77 nM 和 6.49 μM 抑制 JAK2 和 JAK3。

Brepocitinib (PF-06700841) P-Tosylate is a potent dual Janus kinase 1 (JAK1) and TYK2 inhibitor with IC 50 s of 17 nM and 23 nM, respectively. Brepocitinib P-Tosylate also inhibits JAK2 and JAK3 with IC 50 s of 77 nM and 6.49 μM, respectively.

Solid

JAK1 17 nM (IC50) JAK2 77 nM (IC50

Brepocitinib (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). Brepocitinib 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). Brepocitinib 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). Brepocitinib 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 Brepocitinib with IC50s of 305 nM and 86 nM, respectively.

Brepocitinib (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 Brepocitinib 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. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. Fensome A, et al. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700

In Vitro: DMSO : 50 mg/mL (89.03 mM; ultrasonic and warming and heat to 60°C)配制储备液