PARP14 inhibitor 1
PARP14 inhibitor 1 is an orally active, selective PARP14 inhibitor with an IC50 of 5.52 nM. PARP14 inhibitor 1 exhibits favorable pharmacokinetic properties and in vivo safety. PARP14 inhibitor 1 enhances and stabilizes intracellular endogenous PARP14 protein levels, while effectively reducing the expression levels of IL-4, IL-13 and IL-17A. PARP14 inhibitor 1 can be used in research related to atopic dermatitis.
For research use only. We do not sell to patients.
- CAS No.: 3035493-13-8
- Formula: C23H27FN4O3
- Molecular Weight:426.48
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
|
PARP14 5.52 nM (IC50) |
IL-4 |
IL-13 |
IL-17A |
PARP3 2024 nM (IC50) |
PARP5A 1964 nM (IC50) |
PARP5B 1330 nM (IC50) |
PARP7 1973 nM (IC50) |
PARP10 5232 nM (IC50) |
human PARP12 3752 nM (IC50) |
PARP15 916 nM (IC50) |
In Vivo
PARP14 inhibitor 1 (2000 mg/kg; p.o.; single administration) exhibits favorable in vivo safety in BALB/c mice, with no toxicity observed within 10 days[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c mice with Atopic dermatitis (male, n=6 per group, DNCB-induced atopic dermatitis model)[1]
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Dosage:30 mg/kg; 90 mg/kg; 270 mg/kg
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Administration:p.o.; daily; ~14 days
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Result:Reduced dermatitis scores in a dose-dependent manner, with the 90 mg/kg group showing greater improvement than a positive control reference group, and the 270 mg/kg group showing efficacy comparable to another positive control reference group.
Mitigated histopathological skin changes (thickened epidermis/dermis, hyperkeratosis, collagen degeneration, vasodilation, inflammatory cell infiltration) in a dose-dependent manner, with the 270 mg/kg group achieving a histological score similar to the Upadacitinib reference group and superior to the RBN-3143 reference group.
Significantly decreased skin protein levels of IL-4, IL-13, and IL-17A, and serum IgE levels in 90 mg/kg and 270 mg/kg groups, with the 270 mg/kg group showing the lowest cytokine levels.
Reduced skin mRNA expression of IL-4, IL-13, and IL-17A in a dose-dependent manner; the 90 mg/kg group showed greater efficacy than the RBN-3143 (HY-150207) group, and the 270 mg/kg group showed efficacy comparable to the Upadacitinib (HY-19569) group.
Most effectively reduced skin mRNA expression of TSLP and GATA3 in the 270 mg/kg group, with weak regulation of IL-33 mRNA levels.
Showed no significant body weight loss during the study.
Chemical Information
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CAS No. 3035493-13-8
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Molecular Weight 426.48
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Formula C23H27FN4O3
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SMILES
O=C1NC(N2CC3(C2)CCN(CC3)C(C4CC4)=O)=NC5=CC(OCC6CC6)=CC(F)=C51
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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TPA/Croton Oil Ear Edema and Dermatitis
The TPA (12-O-tetradecanoylphorbol-13-acetate) and croton oil-induced mouse ear edema model is a well-established acute cutaneous inflammation system used to evaluate topical anti-inflammatory activity by measuring edema formation, neutrophil infiltration, vascular permeability, and cytokine-mediated skin responses in vivo. The inflammatory response is triggered by topical application of phorbol esters (TPA) or croton oil constituents, leading to rapid activation of protein kinase C signaling, leukocyte recruitment, and increased vascular permeability, which can be quantified by ear thickness, weight, dye extravasation, and biochemical markers such as myeloperoxidase (MPO) activity and pro-inflammatory mediators in ear tissue homogenates. This model is widely used for screening anti-inflammatory agents, where reductions in edema and inflammatory biomarkers reflect suppression of acute dermal inflammation and immune cell infiltration. Histological evaluation typically confirms epidermal
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)