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.

Physicochemical Properties

Molecular Formula	C31H42N6O7
Molecular Weight	610.7
Exact Mass	610.311
Elemental Analysis	C, 60.97; H, 6.93; N, 13.76; O, 18.34
CAS #	136553-81-6
Related CAS #	BQ-123 TFA
PubChem CID	443289
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	1053.6±65.0 °C at 760 mmHg
Flash Point	591.0±34.3 °C
Vapour Pressure	0.0±0.3 mmHg at 25°C
Index of Refraction	1.621
LogP	-0.1
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	44
Complexity	1110
Defined Atom Stereocenter Count	5
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
InChi Key	VYCMAAOURFJIHD-PJNXIOHISA-N
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
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
Synonyms	BQ123; Cyclo(D-trp-D-asp-pro-D-val-leu); BQ-123; BQ 123
HS Tariff Code	2934.99.9001
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.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Endothelin A receptor ( IC50 = 7.3 nM )
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]
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]
Enzyme Assay	BQ-123 is a potent and selective endothelin A receptor (ETAR) antagonist with IC50 of 7.3 nM.
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).
Animal Protocol	Dissolved in 5% NaHCO3; 1 mg/kg; i.v. injection Male Wistar rats
References	[1]. J Cardiovasc Pharmacol . 1992:20 Suppl 12:S11-4. [2]. FEBS Lett . 1992 May 18;302(3):243-6. [3]. Biomed Pharmacother . 2010 Nov;64(9):639-46. [4]. Hum Exp Toxicol . 2014 Oct;33(10):1008-16. [5]. Toxicol Appl Pharmacol . 2015 Feb 1;282(3):275-84.
Additional Infomation	BQ 123 is a cyclic peptide. BQ-123 has been investigated for the basic science and treatment of Coronary Artery Disease, Aorto-coronary Bypass Grafting, and ST-Elevation Myocardial Infarction.

Solubility Data

Solubility (In Vitro)

DMSO: 50~100 mg/mL (81.9~163.7 mM) Water: <1 mg/mL Ethanol: ~15 mg/mL (~24.6 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.