Buloxibutid

Buloxibutid (AT2 receptor agonist C21) is an orally active, selective angiotensin II type 2 receptor (AT2R) agonist, with a K_i value of 0.4 nM for porcine AT2R. Buloxibutid exerts effects such as vasodilation, anti-inflammation, anti-fibrosis (promoting the expression of collagenase MMP-13) and tissue repair mainly by activating the NO/cGMP pathway, inhibiting the pro-proliferative MAPK signaling, and suppressing the pro-fibrotic TGF-β/Smad pathway as well as the inflammatory NF-κB pathway. Buloxibutid can be used in research related to idiopathic pulmonary fibrosis, hypertension, and systemic sclerosis^[1][2][3][4]. IC50 & Target:Ki: 0.4 nM (AT2) and >10 µM (AT1)^[1] In Vitro:Buloxibutid (1-10 μM) inhibits the expression and signaling of proinflammatory pathways in LPS (HY-D1056)-induced THP-1 macrophages in a time- and concentration-dependent manner at concentrations of 1 and 10 μM^[2].
Buloxibutid (Compound 21) (0.1-0.1 μM; 3 days) induces neurite outgrowth in NG108-15 cells by activating AT₂ receptors. After treatment with 0.1 μM for 3 days, it increases the proportion of neurite-positive cells to 19.9%, and its signal transduction depends on the MAPK, cGMP and cGMP-dependent protein kinase pathways^[4].
Buloxibutid (100 nM; 0-1 h) transiently activates p42/p44mapk in NG108-15 cells via activation of the AT₂ receptor, and its phosphorylation level increases by 2.2-fold after treatment with 0.1 μM for 30 min^[4]. In Vivo:Buloxibutid (0.03 mg/kg/day; i.p.; daily administration; for 2 consecutive weeks) prevents and reverses bleomycin (HY-108345)-induced pulmonary fibrosis, vascular remodeling and inflammatory responses in Sprague-Dawley rats^[2].
Buloxibutid (0.3 mg/kg/day; mini pump; daily administration; for 7 consecutive days) alleviates bleomycin-induced pulmonary fibrosis in rats^[2].
Buloxibutid (1 mg/kg; i.p.; single administration) attenuates lung injury and inflammation induced by ventilator-induced lung injury (VILI) in Sprague-Dawley rats^[2].
Buloxibutid (0.3 mg/kg/day; i.p.; daily) alleviates LPS-induced acute lung injury in C57Bl/6 mice^[2].
Buloxibutid (0.3 mg/kg/day; i.p.; daily administration) alleviates hyperoxia-induced acute lung injury in C57Bl/6 mice^[2].
Buloxibutid (0.1-1 mg/kg/day; i.p.; administered daily for 7 consecutive days) reduces acute cigarette smoke-induced inflammation in female BALB/c mice, with the maximum efficacy observed at a dose of 0.3 mg/kg/day^[2].
Buloxibutid (0.3 mg/kg/day; i.p.; daily administration; for 3 consecutive weeks) reduces chronic cigarette smoke-induced inflammation, epithelial injury and profibrotic responses, while improving pulmonary function in BALB/c mice^[2].
Buloxibutid (0.03 mg/kg/day; i.p.; daily administration for 2 consecutive weeks) reverses monocrotaline-induced pulmonary fibrosis and myocardial fibrosis in male Sprague-Dawley rats^[2].
Buloxibutid (0.03 mg/kg; i.p.; once daily; for 14 consecutive days) significantly reduces systolic blood pressure, diastolic blood pressure, and mean blood pressure by 34.4%, 40.2%, and 38.0%, respectively, in male Sprague Dawley rats with hypertension induced by L-NAME/NaCl. It also improves the antioxidant status of the heart and aorta, alleviates histopathological damage to cardiac tissue, and restores normal aortic structure^[3].
Buloxibutid (0.03 mg/kg; i.p.; daily; 14 days) combined with Empagliflozin (HY-15409) significantly improves the antioxidant status of the heart and aorta in male Sprague Dawley rats with hypertension induced by L-NAME/NaCl, reduces aortic MDA levels by 27.5%, restores normal aortic structure, alleviates cardiac histopathological damage, and exerts a synergistic effect on aortic SOD and CAT activities^[3].
Buloxibutid (Compound 21) (0.003-0.3 mg/kg/h; i.v.; continuous infusion; 100 μM; intraluminal perfusion) dose-dependently enhances duodenal mucosal alkaline secretion in male Sprague-Dawley rats via activation of the AT2 receptor, with the maximal effect observed at an intravenous dose of 0.3 mg/kg/h^[4].
Buloxibutid (0.008-4 mg/kg; i.v.; single bolus) induces a significant AT2 receptor-mediated reduction in mean arterial pressure at intravenous doses of 0.008 mg/kg and 0.05 mg/kg in anesthetized spontaneously hypertensive rats^[4].