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Tumor necrosis factor (soluble TNF, TNF-α) is a pro-inflammatory cytokine central to the regulation of immune responses and inflammatory processes. SAR441566 is a first-in-class, orally available small molecule that selectively binds and stabilizes the soluble form of TNF in an inactive state, thereby inhibiting its downstream signaling. This approach mimics the therapeutic outcomes of anti-TNF biologic agents but potentially offers improved convenience and oral dosing. SAR441566 is currently being studied in clinical trials for several autoimmune diseases, including rheumatoid arthritis, ulcerative colitis, Crohn’s disease, and plaque psoriasis. The mechanism of action involves high-affinity binding to TNF (KD ~15 nM) and potent inhibition of TNF-induced immune activation. While its full clinical safety profile is under investigation, the drug acts on the same biological pathway as established TNF inhibitors, warranting standard precautions for infection risks and immunomodulation.
Inhibition of soluble TNF by stabilizing an asymmetrical, inactive TNF trimer conformation, thus blocking downstream proinflammatory signaling
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