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The aim is to develop dual-targeting inhibitors for RIPK1 and RIPK3 to treat systemic inflammatory response syndrome.

Potent Benzothiazole-Triazole RIPK1/RIPK3 Dual-Targeting Inhibitors for the Treatment of Systemic Inflammatory Response Syndrome

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The aim is to develop dual-targeting inhibitors for RIPK1 and RIPK3 to treat systemic inflammatory response syndrome.
Designed novel benzothiazole-triazole derivatives by combining known inhibitors.
Evaluated antinecroptotic activity and cytotoxicity in vitro.
Tested selected compounds in mice models for efficacy in alleviating SIRS symptoms.
Compounds inhibited RIPK1 (Kd < 10 nM) and RIPK3 (Kd = ∼50 nM), demonstrating potent activity.
Compounds improved survival and restored body temperature in SIRS models.
Reduced IL-1β/IL-6 levels in serum and multiple organs, indicating effective anti-inflammatory action.

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Randomized trial shows dual-targeting inhibitors improve outcomes in inflammatory response syndrome, suggesting new therapeutic options.

Hu et al. (2026) studied this question.

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