| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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Purity: ≥98%
BQ-123 (Cyclo(D-trp-D-asp-pro-D-val-leu); BQ123; BQ 123) is a potent and selective antagonist of endothelin A receptor (ETAR) with an IC50 of 7.3 nM. It has been demonstrated that endothelin-1 increases the activity of neurons and glutaminergic synaptic transmission through endothelin-A receptors (ETAR) in the nucleus tractus solitarius neurons, which are crucial in epileptic seizures. Consequently, BQ-123, an ETAR antagonist, may reduce glutaminergic synaptic transmission and neuronal excitability. BQ123 decreases myocardial infarction after focal cerebral ischemia in rats and amplifies hypothermia induced by acetaminophen. In LPS-treated rats, BQ123 Activates Nrf2 to Stimulate Skeletal Muscle Antioxidant Defense. Following surgery for congenital heart disease, BQ123 lowers pulmonary vascular resistance. BQ123 shields against endothelial and myocardial reperfusion damage.
| Targets |
Endothelin A receptor ( IC50 = 7.3 nM )
Endothelin A receptor (ET_A) (Ki = 0.4 nM, human; IC50 = 0.8 nM for ET-1 binding inhibition) [2][3] - Endothelin B receptor (ET_B) (Ki = 680 nM, human; >1700-fold lower affinity than ET_A) [2][3] - No significant affinity for other GPCRs (e.g., angiotensin II, VEGF receptors) (Ki > 10000 nM) [2] |
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| ln Vitro |
In vitro activity: BQ-123 specifically blocks the contraction of ETA-mediated smooth muscle cells in pig aortic vascular smooth muscle cells. [1] BQ-123 inhibits DNA synthesis and phosphoinositide breakdown induced by endothelin-1 in rat vascular smooth muscle cells. [2]
BQ-123 is a potent, highly selective endothelin A receptor (ET_A) antagonist, with negligible activity against ET_B [2][3][5] - In human aortic smooth muscle cells (HASMCs), BQ-123 (0.1-10 μM) dose-dependently inhibited ET-1-induced proliferation by 50-75% and blocked ET_A-mediated Ca²⁺ influx and ERK1/2 phosphorylation [3][5] - In human umbilical vein endothelial cells (HUVECs), BQ-123 (0.5-5 μM) reduced ET-1-induced vascular cell adhesion molecule-1 (VCAM-1) expression by 40-55% and inhibited monocyte-endothelial adhesion [3] - In rat microglial cells (BV2), BQ-123 (1-20 μM) suppressed LPS-induced TNF-α and IL-6 production by 35-50% via blocking ET_A-NF-κB signaling [4] - It had no effect on ET_B-mediated relaxation in isolated rabbit pulmonary arteries at concentrations up to 100 μM [1] |
| ln Vivo |
BQ-123 (1 mg/kg, intravenous) improves myocardial ischemia-reperfusion injury in rats. [3] Pentylenetetrazole (PTZ)-induced tonic-clonic seizures in rats are potently prevented from forming and spreading by BQ-123 (3 mg/kg, i.v.). [4] By inducing uterine and placental IL-10, BQ-123 (6.7 mg/kg, i.p.) protects against LPS-induced preterm birth in pregnant C57BL/6 mice. [5]
In spontaneously hypertensive rats (SHRs), intravenous BQ-123 (0.1-1 mg/kg) dose-dependently reduced mean arterial pressure (MAP) by 15-25% within 30 minutes of administration [1][3] - In a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI), intraperitoneal BQ-123 (5-15 mg/kg) reduced lung inflammation (neutrophil infiltration reduced by 45%) and vascular permeability (edema reduced by 50%) [4] - In rats with cerebral vasospasm induced by subarachnoid hemorrhage (SAH), intracisternal BQ-123 (0.3 mg/kg) attenuated basilar artery constriction by 60% and improved cerebral blood flow [2] - In SHRs, repeated intravenous administration of BQ-123 (0.5 mg/kg/day for 7 days) sustained MAP reduction by 20% without tolerance development [1] |
| Enzyme Assay |
BQ-123 is a potent and selective endothelin A receptor (ETAR) antagonist with IC50 of 7.3 nM.
ET_A/ET_B receptor binding assay: Membrane preparations from human ET_A/ET_B-expressing cells were incubated with [¹²⁵I]-ET-1 (0.1 nM) and BQ-123 (0.001-1000 nM) at 25°C for 90 minutes. Non-specific binding was determined with excess unlabeled ET-1. Bound ligands were separated by filtration, and radioactivity was quantified to calculate Ki values [2][3] - NF-κB activation assay: BV2 microglia were pretreated with BQ-123 (1-20 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 6 hours. Nuclear extracts were analyzed for NF-κB DNA-binding activity by EMSA [4] - ERK1/2 phosphorylation assay: HASMCs were pretreated with BQ-123 (0.1-10 μM) for 1 hour, then stimulated with ET-1 (10 nM) for 15 minutes. ERK1/2 phosphorylation was detected by Western blot and quantified [5] |
| Cell Assay |
BQ123 (10-6 M) blocked endothelin-1 (ET-1) (10-6 M)-induced [Ca2+]i increase in ETA-expressing cells by 95%. BQ-123 prevented ET-1-induced cellular contraction, [Ca2+ ]i mobilization, [3H]thymidine incorporation, MAP kinase activation, and MTT reduction in rat vascular smooth muscle cells (VSMC). However, MAP kinase activity and [Ca2+]i mobilization were not inhibited by BQ-123 in response to angiotensin II (Ang II) or arginine vasopressin (AVP).
Vascular smooth muscle cell proliferation assay: HASMCs were seeded in 96-well plates, pretreated with BQ-123 (0.1-10 μM) for 1 hour, then stimulated with ET-1 (10 nM) for 72 hours. Cell viability was measured by MTT assay [3][5] - Monocyte-endothelial adhesion assay: HUVECs were treated with BQ-123 (0.5-5 μM) plus ET-1 (10 nM) for 24 hours, then co-incubated with fluorescently labeled monocytes. Adhered monocytes were counted by fluorescence microscopy [3] - Microglia cytokine production assay: BV2 cells were seeded in 24-well plates, pretreated with BQ-123 (1-20 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. TNF-α and IL-6 levels were quantified by ELISA [4] - Ca²⁺ influx assay: HASMCs were loaded with calcium-sensitive dye, pretreated with BQ-123 (0.1-10 μM) for 20 minutes, then stimulated with ET-1 (10 nM). Ca²⁺ fluorescence intensity was monitored by fluorometry [5] |
| Animal Protocol |
Dissolved in 5% NaHCO3; 1 mg/kg; i.v. injection
Male Wistar rats Spontaneously hypertensive rat (SHR) model: Male SHRs (250-300 g) were administered BQ-123 dissolved in saline via intravenous injection at 0.1, 0.5, 1 mg/kg (single dose) or 0.5 mg/kg/day for 7 days. Mean arterial pressure was measured by tail-cuff plethysmography [1][3] - LPS-induced acute lung injury (ALI) mouse model: Female C57BL/6 mice (20-25 g) were intraperitoneally injected with LPS (10 mg/kg). BQ-123 (5, 10, 15 mg/kg) dissolved in saline was administered intraperitoneally 1 hour before LPS injection. Lung histopathology and inflammation markers were analyzed [4] - SAH-induced cerebral vasospasm rat model: Male Sprague-Dawley rats (300-350 g) were subjected to SAH by endovascular perforation. BQ-123 (0.3 mg/kg) dissolved in saline was administered via intracisternal injection 24 hours post-SAH. Basilar artery diameter and cerebral blood flow were measured [2] |
| ADME/Pharmacokinetics |
Oral bioavailability: <5% in rats (poor oral absorption; parenteral administration was used in preclinical studies) [3] - Elimination half-life: 2.3 hours in rats (intravenous administration) [3] - Plasma protein binding: 85-90% in human plasma (concentration range: 0.1-10 μg/mL) [3] - Distribution: Volume of distribution (Vd) in rats = 0.8 L/kg, mainly distributed in vascular tissue and brain tissue [2][3] - Metabolism/excretion: metabolized by peptide hydrolysis; within 24 hours, 60% of the dose is excreted in urine as metabolites and 30% in feces [3]
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| Toxicity/Toxicokinetics |
Acute toxicity: The intravenous LD50 in rats was 150 mg/kg; in mice it was 200 mg/kg [3]
- Subchronic toxicity (intravenous administration to SHR rats over 7 days): No significant hepatotoxicity or nephrotoxicity was observed at doses up to 0.5 mg/kg/day; serum creatinine, BUN, and ALT/AST levels remained unchanged [1][3] - No significant cytotoxicity was observed in BV2 microglia and HASMC cells at concentrations up to 50 μM [4][5] - Drug interactions: Preclinical studies have shown that this product has no significant interactions with antihypertensive drugs (such as captopril) or anti-inflammatory drugs (such as dexamethasone) [3][4] |
| References | |
| Additional Infomation |
BQ-123 is a cyclic peptide.
BQ-123 has been used in basic scientific research and treatment of coronary artery disease, aortic coronary artery bypass grafting and ST segment elevation myocardial infarction. BQ-123 is a potent and highly selective ET_A receptor antagonist and a well-established research tool for studying the endothelin signaling pathway [2][3][5]. Its core mechanism is to competitively block the binding of ET-1 to the ET_A receptor, thereby inhibiting downstream signaling pathways (Ca²⁺ influx, ERK1/2, NF-κB) involved in vasoconstriction, cell proliferation and inflammation [3][4][5]. Its research applications include the study of ET_A-mediated diseases (hypertension, cerebral vasospasm, acute lung injury) and the validation of ET_A as a therapeutic target. [1][2][4] -Low oral bioavailability limits its clinical application, but its high selectivity and potency make it an ideal choice for in vitro and parenteral in vivo studies. [3] - It is widely used to elucidate the specific roles of ET_A and ET_B receptors in vascular and inflammatory processes. [2][5] |
| Molecular Formula |
C31H42N6O7
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| Molecular Weight |
610.7
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| Exact Mass |
610.311
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| Elemental Analysis |
C, 60.97; H, 6.93; N, 13.76; O, 18.34
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| CAS # |
136553-81-6
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| Related CAS # |
BQ-123 TFA
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| PubChem CID |
443289
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
1053.6±65.0 °C at 760 mmHg
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| Flash Point |
591.0±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.621
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| LogP |
-0.1
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
44
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| Complexity |
1110
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O=C(N[C@](C(N(CCC1)[C@]1([H])C2=O)=O)([H])CC(O)=O)[C@H](NC([C@@H](NC([C@H](N2)C(C)C)=O)CC(C)C)=O)CC3=CNC4=CC=CC=C34
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| InChi Key |
VYCMAAOURFJIHD-PJNXIOHISA-N
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| InChi Code |
InChI=1S/C31H42N6O7/c1-16(2)12-21-27(40)33-22(13-18-15-32-20-9-6-5-8-19(18)20)28(41)35-23(14-25(38)39)31(44)37-11-7-10-24(37)29(42)36-26(17(3)4)30(43)34-21/h5-6,8-9,15-17,21-24,26,32H,7,10-14H2,1-4H3,(H,33,40)(H,34,43)(H,35,41)(H,36,42)(H,38,39)/t21-,22+,23+,24-,26+/m0/s1
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| Chemical Name |
2-[(3R,6R,9S,12R,15S)-6-(1H-indol-3-ylmethyl)-9-(2-methylpropyl)-2,5,8,11,14-pentaoxo-12-propan-2-yl-1,4,7,10,13-pentazabicyclo[13.3.0]octadecan-3-yl]acetic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6375 mL | 8.1873 mL | 16.3747 mL | |
| 5 mM | 0.3275 mL | 1.6375 mL | 3.2749 mL | |
| 10 mM | 0.1637 mL | 0.8187 mL | 1.6375 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02966665 | Recruiting | Drug: BQ-123 Drug: BQ-123, MitoQ, BH4 |
Heart Failure Hypertension |
Russell Richardson | September 2008 | Phase 1 |
| NCT03679780 | Recruiting | Drug: BQ-123 Drug: BQ-788 Drug: L-Arginine |
Cardiovascular Diseases Vasoconstrictiony |
The University of Texas at Arlington |
October 1, 2018 | Phase 1 |
| NCT00759408 | Completed | Drug: BQ-123 | Pulmonary Hypertension | Brigham and Women's Hospital | February 1999 | Phase 2 |
| NCT02086253 | Completed | Drug: BQ-788 and/or BQ-123 | Healthy Conditions | University Hospital, Rouen | February 2014 | Not Applicable |
| NCT02124824 | Completed | Drug: BQ-123 | Heart Failure | VA Office of Research and Development |
September 1, 2014 | Early Phase 1 |
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