Bz 423

Bz 423 is an inhibitor of mitochondrial complex V, also known as F₁F₀ ATP synthase.¹ It inhibits mitochondrial complex V in isolated bovine heart mitochondria when used at a concentration of 10 µM. Bz 423 (10 µM) induces apoptosis and mitochondrial cytochrome c release in Ramos B cell lymphoma cells.² It induces cell cycle arrest in the G₁ phase in Ramos cells when used at a concentration of 10 µM. Bz 423 (60 mg/kg) induces reactive oxygen species (ROS) production and decreases B cell levels in mouse spleen. It reduces total splenic T cells and Cd4⁺ T cells levels, kidney fibrosis, synovial cell proliferation, and cartilage and subchondral bone erosion in an MRL/Mpj-Fas Ipr mouse model of spontaneous systemic lupus erythematosus (SLE) when administered at a dose of 60 mg/kg every two days.³

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1. Johnson, K.M., Chen, X., Boitano, A., et al. Identification and validation of the mitochondrial F1F0-ATPase as the molecular target of the immunomodulatory benzodiazepine Bz-423. Chem. Biol. 12(4), 485-196 (2005).

2. Blatt, N.B., Bednarski, J.J., Warner, R.E., et al. Benzodiazepine-induced superoxide signals B cell apoptosis: Mechanistic insight and potential therapeutic utility. J. Clin. Invest. 110(8), 1123-1132 (2002).

3. Bednarski, J.J., Warner, R.E., Rao, T., et al. Attenuation of autoimmune disease in Fas-deficient mice by treatment with a cytotoxic benzodiazepine. Arthritis Rheum. 48(3), 757-766 (2003).