Buloxibutid hydrochloride
Based on 6 publication(s) in Google Scholar
Buloxibutid (AT2 receptor agonist C21) hydrochloride is an orally active, selective angiotensin II type 2 receptor (AT2R) agonist, with a Ki value of 0.4 nM for porcine AT2R. Buloxibutid hydrochloride exerts vasodilatory, anti-inflammatory, antifibrotic (promoting the expression of collagenase MMP-13) and tissue repair effects mainly by activating the NO/cGMP pathway, inhibiting the pro-proliferative MAPK signaling, and suppressing the pro-fibrotic TGF-β/Smad pathway and inflammatory NF-κB pathway. Buloxibutid hydrochloride can be used in research related to idiopathic pulmonary fibrosis, hypertension, systemic sclerosis and other conditions.
For research use only. We do not sell to patients.
- CAS No.: 1947313-60-1
- Formula: C23H30ClN3O4S2
- Molecular Weight:512.09
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Publications Citing Use of MedChemExpress (MCE) Buloxibutid hydrochloride
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IF
All Angiotensin Receptor Isoforms
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Biological Activity
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AT2 Receptor 0.4 nM (Ki) |
AT1 Receptor > 10 μM (Ki) |
Buloxibutid (1-10 μM) hydrochloride 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) hydrochloride 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) hydrochloride 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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NG108-15 neuroblastoma-glioma hybrid cells
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Concentration:0.1 nM, 1 nM, 0.1 μM, 1 μM
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Incubation Time:3 days
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Result:Increased the percentage of neurite-positive cells from 5.5% (control) to 19.9% at 0.1 μM treatment.
Induced neurite outgrowth at concentrations ≥ 0.1 nM.
Had its neurite outgrowth effect abolished by co-incubation with PD 123,319.
Had its neurite outgrowth effect reduced by co-incubation with PD 98,059, LY-83,583, or KT 5823.
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Cell Line:NG108-15 neuroblastoma-glioma hybrid cells
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Concentration:100 nM
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Incubation Time:0, 30 and 60 min
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Result:Induced a 2.2-fold increase in phosphorylated p42/p44mapk levels relative to control within 30 min.
Decreased phosphorylated p42/p44mapk levels to basal levels by 60 min.
Had its 30-min activation abolished by pre-incubation with PD 123,319.
Buloxibutid (0.3 mg/kg/day; mini pump; daily administration; for 7 consecutive days) hydrochloride alleviates bleomycin-induced pulmonary fibrosis in rats[2].
Buloxibutid (1 mg/kg; i.p.; single administration) hydrochloride 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) hydrochloride alleviates LPS-induced acute lung injury in C57Bl/6 mice[2].
Buloxibutid (0.3 mg/kg/day; i.p.; daily administration) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley[2]
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Dosage:0.03 mg/kg/day
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Administration:i.p.; daily; 14 days
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Result:Attenuated bleomycin-induced increases in right ventricular systolic pressure (RVSP), associated with reduced cardiac and pulmonary vascular remodeling.
Caused significant reductions in percentage fibrotic area, Ashcroft score, and hydroxyproline content.
Prevented or reversed bleomycin-induced increases in Col1a/3a1, CTGF, MMP-12, TIMP-1, and IL-13 gene expression to baseline levels.
Reduced pro-inflammatory gene expression (CCL2, IL-6, TLR4) and CD68+ macrophage infiltration.
Reduced bleomycin-induced increases in AT2R gene expression.
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Animal Model:Sprague-Dawley[2]
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Dosage:0.3 mg/kg/day
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Administration:subcutaneous; daily; 7 days
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Result:Reduced bleomycin-induced increases in Ashcroft score and percentage interstitial collagen area, slightly more effectively than β-Pro7 Ang III, and with greater efficacy than pirfenidone for these fibrotic measures.
Reduced lung myofibroblast accumulation and TGFβ expression to a similar degree as β-Pro7 Ang III and pirfenidone.
Tended to increase lung compliance relative to the bleomycin group.
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Animal Model:Sprague-Dawley[2]
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Dosage:1 mg/kg
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Administration:i.p.; single dose
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Result:Significantly attenuated ventilation-induced lung damage (histological scoring).
Reduced cell and protein content in bronchoalveolar lavage fluid (BALF).
Caused a significant increase in the anti-inflammatory cytokines IL-4 and IL-10.
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Animal Model:BALB/c (female)[2]
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Dosage:0.1 mg/kg/day; 0.3 mg/kg/day; 1 mg/kg/day
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Administration:i.p.; daily; 7 days
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Result:Exhibited dose-dependent anti-inflammatory effects, reducing cytokines and cells in BALF, with maximal effects observed at the 0.3 mg/kg dose.
Restored alveolar macrophage phagocytic ability at 0.3 mg/kg/day.
Suppressed cigarette smoke-induced pro-inflammatory marker expression at 0.3 mg/kg/day.
Restored M2 phenotypic marker expression at 0.3 mg/kg/day.
Upregulated AT2R and MasR expression at 0.3 mg/kg/day.
Reversed cigarette smoke-induced reductions in AT2R expression.
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Animal Model:BALB/c (female)[2]
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Dosage:0.3 mg/kg/day
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Administration:i.p.; daily; 21 days
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Result:Significantly reduced cigarette smoke-induced increases in pro-inflammatory cytokines and alveolar epithelial thickening.
Opposed pro-fibrotic responses, reducing active TGFβ1, SMAD2/3, hydroxyproline, MMP-9, and MMP-12 levels, though augmented cigarette smoke-induced increases in TIMP-1.
Elicited significant protective effects in all measured lung function parameters.
Reversed cigarette smoke-induced increases in AT2R expression.
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Animal Model:Sprague-Dawley (male)[2]
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Dosage:0.03 mg/kg/day
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Administration:i.p.; daily; 14 days
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Result:Reversed lung interstitial and peri-vascular fibrosis, as well as cardiac fibrosis; this anti-fibrotic effect was abrogated by co-administration with an AT2R antagonist or MasR antagonist.
Reversed monocrotaline-induced increases in ACE gene expression and decreases in ACE2 gene expression, restoring ACE2 to double control levels.
Did not affect AT1R expression but significantly increased AT2R expression relative to monocrotaline-treated and control rats.
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Animal Model:Not specified[2]
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Dosage:2 mg/kg/day; 20 mg/kg/day
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Administration:p.o.; daily; 34 days
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Result:Significantly improved cardiac function.
Reversed remodeling in vessels of all sizes.
Reduced lung collagen content and percentage dense area.
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Animal Model:Sprague Dawley (male, hypertension induced via 40 mg/kg L-NAME i.p. once daily for 28 days plus 1% NaCl in drinking water ad libitum for 28 days)[3]
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Dosage:0.03 mg/kg
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Administration:i.p.; once daily; 14 days
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Result:Reduced systolic blood pressure to a median of 73.77 mmHg, diastolic blood pressure to a median of 57.82 mmHg, and mean blood pressure to a median of 67.465 mmHg compared to the hypertension-only group.
Decreased heart rate to a median of 215.075 beats/min compared to the control group.
Reduced heart weight to a median of 1.177 g compared to the hypertension-only group.
Increased superoxide dismutase activity to a median of 6.303 U/g protein and glutathione peroxidase activity to a median of 79.698 U/mg protein in cardiac tissue compared to the hypertension-only group.
Increased glutathione level to a median of 51.333 μmol/g tissue, superoxide dismutase activity to a median of 16.511 U/g protein, catalase activity to a median of 42.085 K/g protein, and glutathione peroxidase activity to a median of 104.833 U/mg protein in aortic tissue compared to the hypertension-only group.
Increased serum calcium level to a median of 9.95 mg/dL and reduced serum total cholesterol level to a median of 38.5 mg/dL compared to the hypertension-only group.
Reduced cardiac histopathological damage scores for degenerated cardiomyocytes, hemorrhage, inflammatory infiltration, and collagen deposition compared to the hypertension-only group.
Restored thoracic aortic histology to a state similar to the control group, resolving dilatation and elastic lamella irregularities seen in the hypertension-only group.
Chemical Information
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CAS No. 1947313-60-1
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Molecular Weight 512.09
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Formula C23H30ClN3O4S2
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SMILES
O=C(NS(=O)(C1=C(C2=CC=C(CN3C=NC=C3)C=C2)C=C(CC(C)C)S1)=O)OCCCC.Cl
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Synonyms
AT2 receptor agonist C21 hydrochloride
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (6)
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Journal Impact Factor
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Most Recent
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Acta Pharmacol Sin
Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway. [Abstract]2024 Jun;45(6):1201-1213. PMID: 38491160
Buloxibutid hydrochloride purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Jun;45(6):1201-1213. [Abstract]
Representative images of liver tissue sections from wild-type mice (aged 10 days) treated with vehicle or C21 (Buloxibutid; i.p.) 0.3 mg/kg every 12 h for 10 days. The liver-to-body weight ratios were significantly higher in the treatment groups than in the vehicle groups.
Buloxibutid hydrochloride purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Jun;45(6):1201-1213. [Abstract]
Immunohistochemical analysis of Ki-67, Yap, and BrdU expression levels in liver tissue sections from wild-type mice (aged 10 days) treated with vehicle or C21 (Buloxibutid; i.p.) 0.3 mg/kg every 12 h for 10 days.
Buloxibutid hydrochloride purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Jun;45(6):1201-1213. [Abstract]
Immunoblot analysis of the indicated proteins in liver tissue sections from wild-type mice (aged 10 days) treated with vehicle or C21 (Buloxibutid; i.p.) 0.3 mg/kg every 12 h for 10 days. The results showed that p-Yap and p-LATS1 expression levels were significantly lower in the C21-treated groups than in the vehicle groups, suggesting a potential regulatory role for the AT2R in modulation of the Hippo–Yap signaling pathway.
Buloxibutid hydrochloride purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Jun;45(6):1201-1213. [Abstract]
Serum alanine aminotransferase and aspartate aminotransferase levels in wild-type mice (n = 6) at 6 h after treatment with vehicle or C21 (Buloxibutid; 0.3 mg/kg; i.p.; single dose) following exposure to acetaminophen. At 6 h after administration of acetaminophen, serum ALT and AST levels were significantly lower in the C21-treated group than in the vehicle-treated control group.
Buloxibutid hydrochloride purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Jun;45(6):1201-1213. [Abstract]
Immunofluorescence staining of F-actin (red), Yap (green), and DAPI (blue) in AML12 cells treated with C21 (Buloxibutid; 10 μM; 24 h). The result indicated a correlation between cellular F-actin abundance and the nuclear localization of Yap.
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Clin Sci
G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation. [Abstract]2022 Jun 30;136(12):989-1003. PMID: 35695067 -
Cell Mol Life Sci
Involvement of miRNA-204 carried by the exosomes of macrophages in the AT2 receptor-mediated improvement of vascular calcification. [Abstract]2025 Apr 18;82(1):165. PMID: 40249512 -
Eur J Pharmacol
Activation of angiotensin II type 2 receptor attenuates lung injury of collagen-induced arthritis by alleviating endothelial cell injury and promoting Ly6Clo monocyte transition. [Abstract]2023 Feb 15:941:175466. PMID: 36528072 -
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Purity & Documentation
References
[1]. Rein-Hedin E, et al. Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin II type 2 receptor agonist. Clin Transl Sci. 2024;17(2):e13735. [Content Brief]
[2]. Young ON, et al. Investigational insights into the potential of angiotensin type II receptor agonists as therapeutics for idiopathic pulmonary fibrosis. Expert Opin Investig Drugs. 2026;35(1):63-73. [Content Brief]
[3]. Ozhan O, et al. Protective effects of buloxibutid and empagliflozin on hypertension-induced cardiac and vascular injury in rats. J Mol Histol. 2026;57(1):35. Published 2026 Jan 10. [Content Brief]
[4].
Wan Y, et al. Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist. J Med Chem. 2004;47(24):5995-6008.
[Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Buloxibutid hydrochloride Related Classifications
HY-100113A Related Classifications
Powered by Bioz
- Buloxibutid
- 1947313-60-1
- AT2 receptor agonist C21
- Angiotensin Receptor
- p38 MAPK
- TGF-β Receptor
- TGF-beta/Smad
- MMP
- Raynaud's phenomenon
- angiotensin II type 2 receptor
- systemic sclerosis
- C57Bl/6 mice
- AT2R
- BALB/c mice
- idiopathic pulmonary fibrosis
- hypertension
- THP-1 human macrophages
- Sprague-Dawley rats
- Inhibitor
- inhibitor
- inhibit