PF-06700841

Research use only, not for human use.

PF-06700841 is a potent, selective TYK2/JAK1 kinase inhibitor that reduces IL-23 expression and directly attenuates IL-23 signaling via TYK2.

PF-06700841 is a potent, selective TYK2/JAK1 kinase inhibitor that reduces IL-23 expression and directly attenuates IL-23 signaling via TYK2; is under investigation for the treatment of plaque psoriasis and lupus erythematosus.Psoriasis Phase 2 Clinical.

Brepocitinib (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).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 (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 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. Animal Model:Female Lewis rats with induced arthritis Dosage:3 mg/kg, 10 mg/kg, or 30 mg/kg Administration:Oral administration; for 7 consecutive days Result:Increased in paw volume was significantly lower and dose-dependent.

PF-6700841 | PF-841

Angiogenesis

JAK

JAK

Inflammation/Immunology

Psoriasis

1883299-62-4

389.411

C18H21F2N7O

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (321.01 mM)

CN1C=C(C=N1)NC2=NC=CC(=N2)N3CC4CCC(C3)N4C(=O)C5CC5(F)F

((S)-2,2-difluorocyclopropyl)(3-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone

(-20℃)

With Ice Pack

≥ 2 years