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Buloxibutid (AT2 receptor agonist C21) is an orally active, selective angiotensin II type 2 receptor (AT2R) agonist, with a Ki 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.
For research use only. We do not sell to patients.
Buloxibutid (AT2 receptor agonist C21) is an orally active, selective angiotensin II type 2 receptor (AT2R) agonist, with a Ki 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].
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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.
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.
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Reduced bleomycin-induced increases in Ashcroft score and % interstitial collagen area, with slightly greater efficacy than β-Pro7 Ang III. Exhibited higher efficacy than pirfenidone at reducing these fibrotic measures. Reduced lung myofibroblast accumulation and TGFβ expression to a similar extent as β-Pro7 Ang III and pirfenidone. Tended to increase lung compliance relative to the bleomycin group.
Significantly attenuated VILI-induced lung damage. Reduced cell and protein content in BALF. Caused a significant increase in the anti-inflammatory cytokines IL-4 and IL-10.
Exhibited dose-dependent anti-inflammatory effects, with reduced cytokines and cells in BAL fluid; maximal effects were seen with 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.
Significantly reduced cigarette smoke-induced increases in pro-inflammatory cytokines and alveolar epithelial thickening. Opposed cigarette smoke-induced pro-fibrotic responses, reducing active TGFβ1, SMAD2/3, hydroxyproline, MMP-9, and MMP-12 levels; augmented cigarette smoke-induced increase in TIMP-1. Elicited significant protective effects in all measured lung function parameters. Reversed cigarette smoke-induced increases in AT2R expression toward baseline.
Animal Model:
Sprague-Dawley (male; monocrotaline-induced pulmonary hypertension with interstitial fibrosis)[2]
Dosage:
0.03 mg/kg/day
Administration:
i.p.; daily; 2 weeks
Result:
Reversed lung interstitial and peri-vascular fibrosis, as well as cardiac fibrosis; this anti-fibrotic effect was abrogated by co-administration of an AT2R antagonist or MasR antagonist. Reversed monocrotaline-induced increases in ACE gene expression and decreases in ACE2 gene expression, increasing ACE2 to double control levels. Significantly increased AT2R gene expression relative to monocrotaline-treated and control rats.
Animal Model:
Sprague Dawley (male, hypertension induced via 40 mg/kg L-NAME i.p. daily for 28 days plus 1% NaCl in drinking water for 28 days)[3]
Dosage:
0.03 mg/kg
Administration:
i.p.; once daily; 14 days
Result:
Reduced median systolic blood pressure to 73.77 mmHg. Reduced median diastolic blood pressure to 57.82 mmHg. Reduced median mean blood pressure to 67.465 mmHg. Reduced median heart rate to 215.075 beats/min. Reduced median heart weight to 1.177 g. Increased median superoxide dismutase (SOD) activity to 6.303 U/g protein. Increased median glutathione peroxidase (GPx) activity to 79.698 U/mg protein. Increased median glutathione (GSH) level to 51.333 μmol/g tissue. Increased median aortic SOD activity to 16.511 U/g protein. Increased median catalase (CAT) activity to 42.085 K/g protein. Increased median aortic GPx activity to 104.833 U/mg protein. Increased median calcium level to 9.95 mg/dL. Reduced median total cholesterol to 38.5 mg/dL. Reduced median histopathological damage scores for degenerated cardiomyocytes, hemorrhage, inflammatory infiltration, and collagen deposition to 0. Restored thoracic aorta sections to normal histological structure, similar to control group, with no dilatation or irregularities in elastic lamellae.
Animal Model:
Sprague Dawley (male, hypertension induced via 40 mg/kg L-NAME i.p. daily for 28 days plus 1% NaCl in drinking water for 28 days)[3]
Dosage:
0.03 mg/kg (buloxibutid); 7 mg/kg (empagliflozin)
Administration:
i.p. (buloxibutid; once daily; 14 days); p.o. (Empagliflozin; once daily; 14 days)
Result:
Increased median heart rate to 298.69 beats/min. Increased median cardiac SOD activity to 6.476 U/g protein. Increased median cardiac GPx activity to 82.782 U/mg protein. Reduced median total oxidant level (TOS) to 4.01 μmol/L. Reduced median malondialdehyde (MDA) level to 55.23 nmol/g tissue. Increased median aortic GSH level to 50.264 μmol/g tissue. Increased median aortic SOD activity to 18.059 U/g protein. Increased median aortic CAT activity to 63.554 K/g protein. Increased median aortic GPx activity to 110.402 U/mg protein. Increased median calcium level to 10 mg/dL. Increased median total cholesterol to 46 mg/dL. Increased median low-density lipoprotein (LDL) cholesterol to 15 mg/dL. Reduced median chlorine level to 101 mmol/L. Reduced median sodium level to 138 mmol/L. Reduced median histopathological damage scores for degenerated cardiomyocytes, hemorrhage, inflammatory infiltration, with residual inflammatory cell infiltration observed. Restored thoracic aorta sections to normal histological structure, similar to control group, with no dilatation or irregularities in elastic lamellae.
Increased duodenal mucosal alkaline secretion in a dose-dependent manner: 0.003 mg/kg/h induced a small secretion increase, 0.03 mg/kg/h induced a moderate increase, and 0.3 mg/kg/h induced the largest increase (mean change from baseline ~47%). Increased alkaline secretion by mean change from baseline ~30% at 100 μM intraluminal administration. Produced secretory responses that were significantly inhibited by co-administration of the AT2 receptor antagonist PD 123,319.
Reduced mean arterial pressure by a mean of ~25 mmHg within 30 minutes at 0.05 mg/kg i.v., and this effect was attenuated by co-administration of PD 123,319. Decreased mean arterial pressure at low-dose 0.008 mg/kg. Did not produce a statistically significant change in mean arterial pressure compared to vehicle at higher dose 4 mg/kg.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (105.13 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.1025 mL
10.5126 mL
21.0252 mL
5 mM
0.4205 mL
2.1025 mL
4.2050 mL
10 mM
0.2103 mL
1.0513 mL
2.1025 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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