Ambrisentan (BSF 208075; LU 208075)

Alias: LU-208075; BSF-208075; BSF208075; LU208075; BSF 208075; LU 208075; trade name Letairis; Volibris; pulmonext

Cat No.:V1512 Purity: ≥98%

COA Product Data Instructions for use SDS

Ambrisentan (formerly BSF-208075; LU-208075; BSF208075; LU208075; Letairis; Volibris; pulmonext) is a selective antagonist of the endothelin-1 type A receptor (ETA).

Ambrisentan (BSF 208075; LU 208075) Chemical Structure CAS No.: 177036-94-1
Product category: Endothelin Receptor

This product is for research use only, not for human use. We do not sell to patients.

Size	Price	Stock	Qty
10mg
100mg
250mg
500mg
1g
2g
Other Sizes

ADD TO CART CHECKOUT BULK INQUIRY

1-708-310-1919 sales@invivochem.com

Other Forms of Ambrisentan (BSF 208075; LU 208075):

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Ambrisentan (formerly BSF-208075; LU-208075; BSF208075; LU208075; Letairis; Volibris; pulmonext) is a selective antagonist of the endothelin-1 type A receptor (ETA). For the treatment of pulmonary hypertension, ambrisentan has received FDA approval.

Biological Activity I Assay Protocols (From Reference)

Targets

ETA receptor

ln Vitro

In vitro activity: Ambrisentan is an antagonist of the endothelin type A receptor [1]. Nrf2 activation is induced by ambrisentan. After BMEC monolayers were exposed to hypoxia for 24 hours, endothelial permeability increased, and ambrisentan reduced hypoxia-induced BMEC leakage when compared to the vehicle control. When siRNA targeting Nrf2 is transfected into BMEC prior to treatment, these outcomes are reversed[2].

ln Vivo

The liver hydroxyproline content is significantly lower in the Ambrisentan group (18.0 μg/g±6.1 μg/g vs 33.9 μg/g±13.5 μg/g liver, respectively, P=0.014) than in the control group. The Ambrisentan group also showed significantly reduced levels of hepatic fibrosis as determined by Sirius red staining and areas positive for α-smooth muscle actin, a marker of activated hepatic stellate cells (0.46%±0.18% vs 1.11%±0.28%, respectively, P=0.0003; and 0.12%±0.08% vs 0.25%±0.11%, respectively, P=0.047). Furthermore, the Ambrisentan group exhibits a significant 60% and 45% decrease in hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) respectively. There are no appreciable differences in the groups' liver inflammation, steatosis, or endothelin-related mRNA expression. By preventing hepatic stellate cell activation and lowering procollagen-1 and TIMP-1 gene expression, ambrisentan slows the advancement of hepatic fibrosis. Ambrisentan had no effect on steatosis or inflammation[1].

Cell Assay

Cells are randomly assigned to four groups for every BMEC experiment, unless otherwise specified: (1) normoxia vehicle control (Nx-CTRL); (2) normoxia-treated; (3) hypoxia (24 h) control (Hx-CTRL); and (4) hypoxia (24 h) treated. Nrf2 activators are added 24 hours before any hypoxic exposures, as previously mentioned. Protandim (100 μg/mL), methazolamide (125 μg/mL), nifedipine (7 μg/mL), or ambrisentan (40 μg/mL) are the cell treatments. Additionally, Nrf2 siRNA is applied to a subset of cells. In these tests, siRNA is added 24 hours before medication administration. The purpose of the 24-hour hypoxia exposure for BMEC is to guarantee that the cells maintain their siRNA transfection both during the 24-hour hypoxia exposure and during the drug pre-treatment (24 hours in normoxia). On three different days (n=9), data is gathered from a minimum of three distinct cell culture preparations[2].

Animal Protocol

Mice: The experimental group consists of thirteen male FLS-ob/ob mice, weighing 42.88 g±1.74 g and aged 8 weeks. Male FLS-ob/ob mice are randomized at random to either the control (n = 5) or Ambrisentan (n = 8) group at 12 weeks or older. When a conscious animal has a gastric tube that is the right size, intragastric gavage is administered. Through the use of a gastric tube, ambrisentan (2.5 mg/kg daily) is given orally as a bolus every afternoon for four weeks. The group under control receives water treatment. The fourth week involves fasting the animals for four hours, drawing blood from the tail vein, and testing their blood glucose levels. Blood is extracted from the right ventricle and the animals are put to death after four weeks by injection with pentobarbital anesthesia. Plasma samples are kept at -80°C in a frozen state. The fat from the liver and viscera is then weighed, liquid nitrogen-snap frozen, and kept at -80°C for storage. Further liver specimens are embedded in paraffin and fixed in 10% buffered formalin for histological examination.

References

[1]. Antifibrotic effects of Ambrisentan, an endothelin-A receptor antagonist, in a non-alcoholic steatohepatitis mouse model. World J Hepatol. 2016 Aug 8;8(22):933-41.

[2]. Nrf2 activation: a potential strategy for the prevention of acute mountain sickness. Free Radic Biol Med. 2013 Oct;63:264-73.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C22H22N2O4
Molecular Weight	378.42
Exact Mass	378.16
Elemental Analysis	C, 69.83; H, 5.86; N, 7.40; O, 16.91
CAS #	177036-94-1
Related CAS #	Ambrisentan sodium; 1386915-48-5; Ambrisentan-d10; 1046116-27-1
Appearance	Solid powder
SMILES	CC1=CC(=NC(=N1)O[C@H](C(=O)O)C(C2=CC=CC=C2)(C3=CC=CC=C3)OC)C
InChi Key	OUJTZYPIHDYQMC-LJQANCHMSA-N
InChi Code	InChI=1S/C22H22N2O4/c1-15-14-16(2)24-21(23-15)28-19(20(25)26)22(27-3,17-10-6-4-7-11-17)18-12-8-5-9-13-18/h4-14,19H,1-3H3,(H,25,26)/t19-/m1/s1
Chemical Name	(2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoic acid
Synonyms	LU-208075; BSF-208075; BSF208075; LU208075; BSF 208075; LU 208075; trade name Letairis; Volibris; pulmonext
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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: 76~100 mg/mL (200.8~264.3 mM)

Water: <1 mg/mL

Ethanol: 7.1~22 mg/mL (18.9~58.1 mM)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6426 mL	13.2128 mL	26.4257 mL
	5 mM	0.5285 mL	2.6426 mL	5.2851 mL
	10 mM	0.2643 mL	1.3213 mL	2.6426 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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Calculate Reset

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculate Reset

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Calculate Reset

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate Reset

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

Calculate Reset

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.

Note： (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.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05437224	Completed	Drug: Ambrisentan	Pulmonary Arterial Hypertension	RenJi Hospital	December 18, 2018	Phase 3
NCT01330108	Completed	Drug: ambrisentan	Pulmonary Arterial Hypertension	University of Alabama at Birmingham	May 2011	Phase 4
NCT01072669	Completed	Drug: ambrisentan	Ischemia	Soumya Chatterjee	February 2010	Not Applicable
NCT01224210	Completed	Drug: Ambrisentan	Portopulmonary Hypertension	Tufts Medical Center	March 2010	Phase 3

Biological Data

Histological analyses of liver tissues. Representative images of hematoxylin-eosin staining (magnification, × 100) in the (A) control and (B) ambrisentan groups; representative images of oil red O staining (magnification, × 100) in the (C) control and (D) ambrisentan groups; E: The proportion (%) of the hepatic steatosis area stained with oil red O was measured using image analysis. World J Hepatol . 2016 Aug 8;8(22):933-41.

Immunohistochemistry overlay of Nrf2 activation in rats treated for 4 days with vehicle control, acetazolamide (40 mg/kg), verapamil (10mg/kg), Protandim (10 mg/kg), methazolamide (4 mg/kg), nifedipine (2 mg/kg), or ambrisentan (1 mg/kg). Free Radic Biol Med . 2013 Oct:63:264-73.

Analysis of Nrf2 nuclear concentration in Bovine Brain Microvascular Endothelial (BMEC) cells treated for 24 h with Protandim (125 μg/mL), methazolamide (100 μg/mL), nifedipine (7.5 μg/mL), or ambrisentan (40 μg/mL). Free Radic Biol Med . 2013 Oct:63:264-73.