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WEHI-345 is a potent and selective RIPK2 inhibitor which shows NOD signalling events yet prevents inflammatory cytokine production. WEHI-345 delays RIPK2 ubiquitylation and NF-κB activation downstream of NOD engagement. WEHI-345 proved to be highly specific for RIPK2(Kd=46 nM) and displayed negligible activity (>10 μM) against RIPK1, RIPK4 and RIPK5.
WEHI-345 (500 nM; 0 hour, 2 hours, 4 hours, 8 hours; BMDMs or THP-1 cells) potently blocks MDP-induced transcription of the inflammatory mediators TNF and interleukin-6 (IL-6) in bone marrow-derived macrophages (BMDMs). In THP-1 cells, WEHI-345 reduces mRNA levels of NF-kB targets such as TNF, IL-8, IL-1b and A20.
In vivo, WEHI-345 ameliorates experimental autoimmune encephalomyelitis in mice. WEHI-345 also potently inhibited MDP-induced cytokine and chemokine secretion in the mouse macrophage Raw 264.7 cell line. WEHI-345 (20 mg/kg; intraperitoneal injection; twice daily; for 6 days; C57BL/6 male mice) treatment reduces disease score, inflammatory infiltrate, histological score and recruitment of dendritic cells to the site of inflammation.
Mol Med Rep. 2024 Jan ;36.
Mettl3‑mediated m6A RNA methylation regulates osteolysis induced by titanium particles
WEHI-345 purchased from AbMole
| Molecular Weight | 401.46 |
| Formula | C22H23N7O |
| CAS Number | 1354825-58-3 |
| Solubility (25°C) | DMSO 25 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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