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UH15-38

Chemical Structure : UH15-38

CAS No.: 2540881-21-6

UH15-38 (UH 15-38)

Catalog No.: PC-22143Not For Human Use, Lab Use Only.

UH15-38 is a potent, specific receptor interacting protein kinase 3 (RIPK3) inhibitor with IC50 of 20 nM in NanoBRET assays, potently and selectively blocks IAV-triggered necroptosis in alveolar epithelial cells in vivo.

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Purity & Documentation Purity: 99.7% (HPLC) Select Batch:

Biological Activity

UH15-38 is a potent, specific receptor interacting protein kinase 3 (RIPK3) inhibitor with IC50 of 20 nM in NanoBRET assays, potently and selectively blocks IAV-triggered necroptosis in alveolar epithelial cells in vivo.
UH15-38 blocks TNF-induced necroptosis in primary mouse embryonic fibroblasts (MEFs) with IC50 of 98 nM, 8.5-fold lower than those of GSK′843 (IC50 = 843 nM) and around sixfold lower than those of GSK′872.
UH15-38 prevents phosphorylation of MLKL following necroptotic stimulation by TNF, also robustly inhibits necroptosis in a panel of human and mouse cell lines.
UH15-38 exhibits selectivity for RIPK3-driven necroptotic cell death, displays no significant activity against RIPK1 kinase-driven caspase-8-dependent cell death, also does not inhibit gasdermin D cleavage or pyroptosis upon canonical activation of the NLRP3 inflammasome by nigericin.
UH15-38 does not significantly inhibit a panel of 50 critical protein targets, as well as clean profile against a panel of 90 non-mutant human kinases (DiscoverX KinomeScan).
UH15-38 (1 uM) selectively blocks IAV-induced necroptosis in type I alveolar epithelial cells (AECs), protects type I AECs from canonical TNF-induced necroptosis with IC50 of 114 nM.
UH15-38 a highly potent inhibitor of IAV-induced necroptosis in primary type I AECs (IC50 =39.5 nM) and primary MEFs (IC50 =51.9 nM), respectively.
UH15-38 (30 mg/kg) ameliorates lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, prevents necroptosis, inflammation, and injury in IAV-infected lungs.
UH15-38 does not alter the extent of virus replication and spread or the rate of virus clearance from infected lungs.

Physicochemical Properties

M.Wt 441.54
Formula C26H27N5O2
Appearance Solid
CAS No.
Storage
Solide Powder
-20°C 12 Months; 4°C 6 Months
In Solvent
-80°C 6 Months; -20°C 6 Months
Shipping
Solubility

10 mM in DMSO

Chemical Name/SMILES

3-(3-hydroxyphenyl)-1-methyl-7-((3-(4-methylpiperazin-1-yl)phenyl)amino)-1,6-naphthyridin-2(1H)-one

References

1. Gautam A, et al. Nature. 2024 Apr 10. doi: 10.1038/s41586-024-07265-8.

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