YYSW001
YYSW001 is a selective and orally acrive JAK1 inhibitor with an IC50 of 6 nM and a Kd of 32.32 μM. YYSW001 blocks JAK1-dependent phosphorylation of STAT6, as well as IL-6-induced phosphorylation of STAT3. YYSW001 suppresses pro-inflammatory cytokine levels, reduces paw swelling, lowers clinical arthritis scores, alleviates joint damage and decreases bone loss. YYSW001 is applicable for the research of rheumatoid arthritis.
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- CAS No.: 2763672-36-0
- Formule: C18H20F5N5O
- Masse moléculaire:417.38
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
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JAK1 |
STAT3 |
STAT6 |
YYSW001 (2 h) potently inhibits the JAK1-dependent STAT6 pathway in THP-1 cells (IC50 = 0.041 μM), while only exerting weak inhibitory activity against the JAK2-dependent STAT5 pathway in TF-1 cells (IC50 = 5.530 μM)[1].
YYSW001 (72 h) potently inhibits the proliferation of Ba/F3-TEL-JAK1 cells (IC50 = 290.2 nM), while exhibits extremely low activity against Ba/F3-TEL-JAK2, Ba/F3-TEL-JAK3 and Ba/F3-TEL-TYK2 cells[1].
YYSW001 (15 min) inhibits IL-6-induced JAK1-dependent STAT3 phosphorylation in human whole blood cells (IC50 = 7065.0 nM in CD3+ T cells, 3001.0 nM in CD14+ monocytes), and shows extremely weak inhibitory activity against GM-CSF-induced JAK2-dependent STAT5 phosphorylation[1].
YYSW001 exhibits favorable in vitro ADME properties, including excellent liver microsomal stability and plasma stability, extremely low inhibitory activity against CYP3A4 and hERG, moderate permeability, and moderate plasma protein binding rate[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ba/F3-engineered cell lines (Ba/F3-TEL-JAK1, Ba/F3-TEL-JAK2, Ba/F3-TEL-JAK3, Ba/F3-TEL-TYK2)
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Concentration:serial 2- or 3-fold dilutions (nine gradients)
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Incubation Time:72 h
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Result:Exhibited potent inhibitory activity against Ba/F3-TEL-JAK1 cells with an IC50 of 290.2 nM.
Showed negligible inhibition against Ba/F3-TEL-JAK2, Ba/F3-TEL-JAK3, and Ba/F3-TEL-TYK2 cells (IC50 > 10000.0 nM for all three cell lines).
Achieved a cellular JAK1/JAK2 selectivity ratio of 38.6.
| Species | Dose | Route | AUC0-t | AUC0-∞ | Cmax | Tmax | T1/2 | MRT0-∞ | V | CL | F | Vd |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 3 mg/kg | i.v. | 3831.25 h·μg/L | 4051.12 h·μg/L | / | / | 2.8 h | 3.7 h | / | 0.7 L/h/kg | / | 3.1 L/kg |
| Rat[1] | 3 mg/kg | p.o. | 2277.65 h·μg/L | 2503.58 h·μg/L | 328.61 μg/L | 3.0 h | 2.8 h | 5..8 h | 5.0 L/kg | 1.2 L/h/kg | 61.8 % | / |
| Rat[1] | 10 mg/kg | p.o. | 8543.24 h·μg/L | 8861.88 h·μg/L | 1323.53 μg/L | 3.2 h | 2.2 h | 5.0 h | 3.6 L/kg | 1.1 L/h/kg | 65.6 % | / |
| Rat[1] | 30 mg/kg | p.o. | 25905.37 h·μg/L | 26291.77 h·μg/L | 3300.77 μg/L | 2.9 h | 2.5 h | 6.6 h | 3.3 L/kg | 0.9 L/h/kg | 64.9 % | / |
YYSW001 (1-30 mg/kg; p.o.; twice daily; 14 days) exhibits a clear dose-dependent anti-arthritic effect in a rat adjuvant-induced arthritis model[1].
YYSW001 (100-200 mg/kg; p.o.; once daily; 7 days) shows no significant safety concerns in rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (SD) rats (collagen-induced arthritis model)[1]
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Dosage:3 mg/kg; 10 mg/kg
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Administration:i.g.; twice daily; 14 days
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Result:Reversed disease-induced body weight loss.
Significantly reduced hind paw swelling
Decreased clinical arthritis scores.
Suppressed serum levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α to near-normal levels.
Substantially preserved joint architecture and reduced bone loss compared to the vehicle group.
Chemical Information
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CAS No. 2763672-36-0
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Masse moléculaire 417.38
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Formule C18H20F5N5O
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SMILES
O[C@@H](C1=NC2=CN=C3NC=CC3=C2N1[C@@H]4CN(CC4)CCC(C(F)(F)F)(F)F)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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