Cat. No.: HY-100113

Buloxibutid

(Synonyms: AT2 receptor agonist C21)

5 Cited Publications

Customer Review

Based on 5 publication(s) in Google Scholar

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.

For research use only. We do not sell to patients.

Purity: 98.94%
CAS No.: 477775-14-7
Formula: C₂₃H₂₉N₃O₄S₂
Molecular Weight:475.62

Storage:

Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month

Buloxibutid Chemical Structure

CAS No.: 477775-14-7

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Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (5)
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

IC₅₀ & Target^[4]

AT2 Receptor

0.4 nM (Ki)

AT1 Receptor

> 10 μM (Ki)

All Angiotensin Receptor Isoforms :

All p38 MAPK Isoforms :

All TGF-beta/Smad Isoforms :

Smad1
Smad3

All TGF-β Receptor Isoforms :

All MMP Isoforms :

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Differentiation Assay^[4]

Cell Line:

NG108-15 neuroblastoma-glioma hybrid cells
Concentration:

0.1 nM、1 nM、0.1 μM、1 μM
Incubation Time:

3 days
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.

Western Blot Analysis^[4]

Cell Line:

NG108-15 neuroblastoma-glioma hybrid cells
Concentration:

100 nM
Incubation Time:

0, 30 and 60 min
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.

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.

Animal Model:

Sprague-Dawley (bleomycin-induced pulmonary fibrosis)^[2]
Dosage:

0.03 mg/kg/day
Administration:

i.p.; daily; 2 weeks
Result:

Attenuated bleomycin-induced increases in right ventricular systolic pressure (RVSP).
Reduced cardiac and pulmonary vascular remodeling.
Caused significant reductions in % fibrotic area, Ashcroft scoring, 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.
Mitigated inflammatory responses, reducing pro-inflammatory gene expression (CCL2, IL-6, TLR4) and infiltration of CD68+ macrophages.
Reduced bleomycin-induced increases in AT₂R gene expression.

Animal Model:

Sprague-Dawley (bleomycin-induced pulmonary fibrosis)^[2]
Dosage:

0.3 mg/kg/day
Administration:

minipump; daily; 7 days
Result:

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.

Animal Model:

Sprague-Dawley (ventilation-induced lung injury)^[2]
Dosage:

1 mg/kg
Administration:

i.p.; single dose
Result:

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.

Animal Model:

BALB/c (female; acute cigarette smoke-induced chronic obstructive pulmonary disease)^[2]
Dosage:

0.1 mg/kg/day; 0.3 mg/kg/day; 1 mg/kg/day
Administration:

i.p.; daily; 7 days
Result:

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.

Animal Model:

BALB/c (chronic cigarette smoke-induced chronic obstructive pulmonary disease)^[2]
Dosage:

0.3 mg/kg/day
Administration:

i.p.; daily; 3 weeks
Result:

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.

Animal Model:

Sprague-Dawley (male, nonfasted, surgically isolated duodenal segments)^[4]
Dosage:

0.003-0.3 mg/kg/h; 100 μM
Administration:

i.v.; continuous infusion; intraluminal perfusion
Result:

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.

Animal Model:

Spontaneously hypertensive (SHR, male, anesthetized)^[4]
Dosage:

0.008 mg/kg; 0.05 mg/kg; 4 mg/kg
Administration:

i.v.; single bolus
Result:

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.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 477775-14-7
Appearance Solid
Molecular Weight 475.62
Formula C₂₃H₂₉N₃O₄S₂
Color White to yellow
SMILES

O=C(OCCCC)NS(=O)(C1=C(C2=CC=C(CN3C=CN=C3)C=C2)C=C(CC(C)C)S1)=O
Synonyms

AT2 receptor agonist C21
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (5)

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Journal Impact Factor

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
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
Dokkyo Medical Journal

2023 Sep 8.

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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

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.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.08 mg/mL (4.37 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO 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.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.08 mg/mL (4.37 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.08 mg/mL (4.37 mM); Clear solution

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 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

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).

Working solution concentration: 0.22 mg/mL

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (298 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.1025 mL	10.5126 mL	21.0252 mL	52.5630 mL
	5 mM	0.4205 mL	2.1025 mL	4.2050 mL	10.5126 mL
	10 mM	0.2103 mL	1.0513 mL	2.1025 mL	5.2563 mL
	15 mM	0.1402 mL	0.7008 mL	1.4017 mL	3.5042 mL
	20 mM	0.1051 mL	0.5256 mL	1.0513 mL	2.6281 mL
	25 mM	0.0841 mL	0.4205 mL	0.8410 mL	2.1025 mL
	30 mM	0.0701 mL	0.3504 mL	0.7008 mL	1.7521 mL
	40 mM	0.0526 mL	0.2628 mL	0.5256 mL	1.3141 mL
	50 mM	0.0421 mL	0.2103 mL	0.4205 mL	1.0513 mL
	60 mM	0.0350 mL	0.1752 mL	0.3504 mL	0.8760 mL
	80 mM	0.0263 mL	0.1314 mL	0.2628 mL	0.6570 mL
	100 mM	0.0210 mL	0.1051 mL	0.2103 mL	0.5256 mL

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Buloxibutid

GPCR/G Protein Compound Library

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Kinase Inhibitor Library

MAPK Compound Library

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Publications Citing Use of MedChemExpress (MCE) Buloxibutid

All Angiotensin Receptor Isoforms

All p38 MAPK Isoforms

All TGF-beta/Smad Isoforms

All TGF-β Receptor Isoforms

All MMP Isoforms

Biological Activity

Chemical Information

Publications (5)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Buloxibutid Related Classifications

Cat. No.: HY-100113