XW-17
XW-17 is a PARP14 inhibitor with an IC50 of 3.03 nM and selectivity over other PARP family members.XW-17 suppresses PARP14-mediated mono-ADP-ribosylation, engages and stabilizes endogenous PARP14 protein.XW-17 attenuates skin lesions and decreases expression of IL-4, IL-13, IgE, and IL-17A in an atopic dermatitis-like mouse model.XW-17 can be used for the research of atopic dermatitis.
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- Formule: C24H30N6O3
- Masse moléculaire:450.53
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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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PARP14 |
XW-17 (1 h) potently and selectively inhibits purified PARP14 enzyme activity with an IC50 of 3.03 nM, showing a selectivity index exceeding 9900 over PARP1[1].
XW-17 shows excellent metabolic stability across rat plasma, mouse liver microsomes, rat liver microsomes, and human liver microsomes, with T1/2 values greater than 240 min in all tested systems[1].
XW-17 (5 μM; 2 h) exhibits satisfactory membrane permeability and low efflux in MDCK and Caco-2 cell models, with Papp A→B values of 16.32 × 10-6 cm/s and 20.49 × 10-6 cm/s, respectively[1].
XW-17 (0.001-3 μM; unspecified duration) engages and stabilizes endogenous PARP14 in IFN-γ-stimulated CFPAC-1 cells with an EC50 of 59.5 nM[1].
XW-17 (0.01-1 μM; 6 h pretreatment, 24 h IFN-γ stimulation) potently inhibits PARP14-mediated MARylation in a concentration-dependent manner in IFN-γ-stimulated CFPAC-1 and RAW264.7 cells[1].
XW-17 (up to at least 30 μM; 72 h) shows no significant cytotoxicity toward MCF-10A and AML-12 cells, with IC50 values greater than 30 μM[1].
XW-17 (5-30 μM) has low hERG potassium channel inhibitory activity, with 3.15% inhibition at 5 μM and 5.56% inhibition at 30 μM, indicating low cardiotoxicity risk[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:CFPAC-1 cells
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Concentration:0.001-3 μM
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Incubation Time:unspecified duration (IFN-γ stimulation)
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Result:Induced a concentration-dependent upregulation of PARP14 protein expression, confirming target binding and stabilization, with an EC50 of 59.5 nM.
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Cell Line:CFPAC-1 cells, RAW264.7 cells
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Concentration:0.01-1 μM
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Incubation Time:6 h pretreatment; 24 h IFN-γ stimulation
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Result:Reduced intracellular MARylation signals in a concentration-dependent manner in both cell lines, indicating inhibition of endogenous PARP14 catalytic activity.
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Cell Line:MCF-10A human mammary epithelial cells, AML-12 mouse hepatocytes
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Concentration:up to at least 30 μM
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Incubation Time:72 h
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Result:Did not exhibit significant cytotoxicity, with IC50 values exceeding 30 μM in both cell lines.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (male, 18−22 g, DNCB-induced atopic dermatitis)[1]
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Dosage:25 mg/kg; 50 mg/kg; 100 mg/kg
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Administration:i.p.; twice daily; 11 days
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Result:Significantly reduced dermatitis score compared to model group at 25 mg/kg (P < 0.05), 50 mg/kg (P < 0.01), and 100 mg/kg (P < 0.001).
Achieved lower dermatitis score than positive controls RBN-3143 and Upadacitinib at 100 mg/kg.
Dose-dependently reduced histopathological abnormalities in dorsal skin, with 100 mg/kg dose achieving lowest histological score and outperforming Upadacitinib.
Significantly reduced protein levels of IL-4, IL-13, IL-17A in skin homogenates and serum IgE at 50 mg/kg and 100 mg/kg, with most pronounced inhibition at 100 mg/kg.
Dose-dependently suppressed mRNA levels of IL-31, TSLP, and GATA3 in dorsal skin.
Showed no significant effect on Th1 pathway-related cytokines (TNF-α, IL-6, IL-1β) at any dose.
Caused no significant body weight loss or histological abnormalities in major organs (heart, liver, spleen, lung, kidney).
Chemical Information
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Masse moléculaire 450.53
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Formule C24H30N6O3
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SMILES
CN1C=C(C=N1)CN2CCC(CC2)NC(CC3=NNC(C4=CC=C(C=C43)OCC5CC5)=O)=O
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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)
XW-17 Related Classifications
HY-183548 Related Classifications
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