BBS-4

BBS-4 is a potent and selective inducible nitric oxide synthase (NOS2) dimerization inhibitor, with an IC₅₀ of 0.49 nM. BBS-4 can protect mice from the cardiovascular dysfunction of sepsis^[1]. IC50 & Target: IC50: 0.49 nM (NOS2)^[1] In Vitro: BBS-4 exhibits ∼300–2000-fold selective for inhibiting iNOS dimerization in cells versus CYP-3A4 (∼150 nM in a microsomal benzyloxyresorufin assay; ∼1 μM in a cell-based testosterone hydroxylase assay)^[2]. In Vivo: BBS-4 (10 mg/kg; i.p.; 1 h after endotoxin administration) prevents endotoxin-induced hypotension in mice^[1].
BBS-4 (30 mg/kg; i.p.; 1 h after endotoxin administration) prevents endotoxin-induced myocardial dysfunction in mice^[1].
BBS-4 (10 mg/kg; i.p.; 1 and 8 h after endotoxin administration) prevents endotoxin-induced impairment of murine hypoxic pulmonary vasoconstriction (HPV)^[1].
BBS-4 (10 mg/kg; i.p.; 1 and 8 h after endotoxin administration) does not affect the endotoxin-induced increase in pulmonary NOS2 gene expression, but it (30 mg/kg) prevents cardiac and pulmonary NOS2 protein dimerization and increases plasma nitrate and nitrite (NOx) concentration in mice^[1].
BBS-2 (30 mg/kg; s.c. twice daily for 10 d) does not affect agonist-stimulated NOS3-dependent aortic relaxation ex vivo^[1].
BBS-4 (10-30 mg/kg; i.p.) does not improve mortality rate in endotoxemic mice^[1].