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Apostatin-1 (Apt-1) is a potent TRADD inhibitor. Apostatin-1 can bind with TRADD-N (KD=2.17 μM), disrupting its binding to both TRADD-C and TRAF2. Apostatin-1 modulates the ubiquitination of RIPK1 and beclin 1. Apostatin-1 blocks apoptosis and restores cellular homeostasis by activating autophagy in cells with accumulated mutant tau, α-synuclein, or huntingtin[1]. Apostatin-1 inhibits Velcade (Bortezomib, 0)-induced apoptosis and RIPK1-dependent apoptosis (RDA) and necroptosis, with an IC50 of 0.97 μM[1].Apostatin-1 (10 μM, 6 h) effectively induces autophagy and the degradation of long-lived proteins[1]. Apostatin-1 (20 mg/kg, IP, once) inhibits inflammatory responses, and increases survival of systemic inflammation mouse model[1].

[1]. Xu D, et al. Modulating TRADD to restore cellular homeostasis and inhibit apoptosis. Nature. 2020 Nov;587(7832):133-138.