2. Cell Cycle/DNA Damage Epigenetics
  3. PARP
  4. 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.

For research use only. We do not sell to patients.

XW-17

XW-17 Chemical Structure

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XW-17 Related Antibodies

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PARP PARP1 PARP2 PARP3 PARP4 TNKS1/PARP5A TNKS2/PARP5B PARP7 PARP10 PARP14 PARP15 PARP12 PARP16

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Description

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[1].

IC50 & Target

PARP14

 

In Vitro

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.

XW-17 Related Antibodies

Western Blot Analysis[1]

Cell Line: CFPAC-1 cells
Concentration: 0.001-3 μM
Incubation Time: unspecified duration (IFN-γ stimulation)
Result: Induced a concentration-dependent upregulation of PARP14 protein expression, confirming target binding and stabilization, with an EC50 of 59.5 nM.

Western Blot Analysis[1]

Cell Line: CFPAC-1 cells, RAW264.7 cells
Concentration: 0.01-1 μM
Incubation Time: 6 h pretreatment; 24 h IFN-γ stimulation
Result: Reduced intracellular MARylation signals in a concentration-dependent manner in both cell lines, indicating inhibition of endogenous PARP14 catalytic activity.

Cell Cytotoxicity Assay[1]

Cell Line: MCF-10A human mammary epithelial cells, AML-12 mouse hepatocytes
Concentration: up to at least 30 μM
Incubation Time: 72 h
Result: Did not exhibit significant cytotoxicity, with IC50 values exceeding 30 μM in both cell lines.
In Vivo

XW-17 (25-100 mg/kg; i.p.; twice daily; 11 days) dose-dependently ameliorates DNCB-induced atopic dermatitis in male BALB/c mice, with the 100 mg/kg i.p. twice daily dose achieving the greatest reduction in dermatitis scores, histopathological damage, and Th2/Th17-associated inflammatory mediators, outperforming positive controls RBN-3143 and Upadacitinib[1].

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

Animal Model: BALB/c (male, 18−22 g, DNCB-induced atopic dermatitis)[1]
Dosage: 25 mg/kg; 50 mg/kg; 100 mg/kg
Administration: i.p.; twice daily; 11 days
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).
Molecular Weight

450.53

Formula

C24H30N6O3
SMILES

CN1C=C(C=N1)CN2CCC(CC2)NC(CC3=NNC(C4=CC=C(C=C43)OCC5CC5)=O)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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XW-17 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

XW-17XW17XW 17PARPpoly ADP ribose polymerasemono-ADP-ribosylationIL-17AIL-13atopic dermatitisCaco-2IL-4CFPAC-1PARP14MDCKIgEInhibitorinhibitorinhibit

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