Ambrisentan

• CAS: 177036-94-1
• Catalog Number: ACM177036941
• Category: Main Products
• Molecular Weight: 378.42
• Molecular Formula: C₂₂H₂₂N₂O₄
• Synonyms: (S)-2-(4,6-Dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoic acid; UNII-HW6NV07QEC; Letairis; Ambrisentan
• IUPAC Name: (2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoicacid
• Canonical SMILES: CC1=CC(=NC(=N1)OC(C(=O)O)C(C2=CC=CC=C2)(C3=CC=CC=C3)OC)C
• InChI Key: OUJTZYPIHDYQMC-LJQANCHMSA-N
• Boiling Point: 551.1ºC at 760mmHg
• Flash Point: 287.1ºC
• Density: 1.228g/cm³
• Appearance: off-white crystalline powder
• Exact Mass: 378.15800

Case Study

Ambrisentan for the Reduction of Proteinuria in Alport Syndrome

Song Z, et al. Kidney International Reports, 2024, 9(10), 3067-3069.

Ambrisentan, a selective endothelin A receptor antagonist, has demonstrated significant potential in addressing proteinuria in Alport syndrome (AS), an inherited glomerular disease caused by COL4A3/4/5 gene mutations. AS frequently progresses to kidney failure, with limited therapeutic options available beyond renin-angiotensin-aldosterone system (RAAS) inhibition.
A pilot study explored the use of ambrisentan (5-10 mg daily) in 12 AS patients. Over two months, proteinuria levels decreased by 23.43% ± 5.11%, with no significant decline in renal function, as the estimated glomerular filtration rate (eGFR) remained stable. Continued administration for six months revealed a further reduction in proteinuria by 36.61% ± 16.06% from baseline, with eGFR stability maintained. Adverse events, including edema and headaches, led to discontinuation in 4 of 12 patients, highlighting the need for careful monitoring during early treatment.
This study positions ambrisentan as a promising adjunct to RAAS inhibitors in reducing proteinuria in AS, warranting further investigation in large-scale trials to confirm its efficacy and safety profile.

Ambrisentan for Mitigating Blood-Brain Barrier Disruption and Cerebral Edema in Traumatic Brain Injury

Michinaga S, et al. Neuropharmacology, 2020, 175, 108182.

Ambrisentan, a selective endothelin A (ETA) receptor antagonist, exhibits therapeutic potential in managing blood-brain barrier (BBB) dysfunction and brain edema associated with traumatic brain injury (TBI). TBI, characterized by immediate physical disruption of brain tissue, triggers BBB breakdown and cerebral edema, with elevated endothelin-1 (ET-1) levels playing a critical role in exacerbating brain damage.
In a mouse model of TBI induced by lateral fluid percussion injury (FPI), early administration of ambrisentan (0.1 or 0.5 mg/kg/day) at 6 and 24 hours post-injury significantly improved BBB integrity and reduced cerebral edema. However, delayed treatment initiated two days post-injury did not exhibit significant effects, highlighting the importance of timely intervention. Unlike bosentan, a dual ETA/ETB antagonist, ambrisentan did not reduce ET-1 or ETB receptor expression, suggesting its efficacy is limited to selective ETA receptor blockade.

Ambrisentan-Loaded Lipid-Core Nanocapsules for Pulmonary Arterial Hypertension Treatment

Zancan L. R, et al. International Journal of Pharmaceutics, 2021, 610, 121181.

Ambrisentan (AMB) is a lipophilic orphan drug approved for oral administration to treat pulmonary arterial hypertension (PAH). To enhance its therapeutic efficacy and oral bioavailability, AMB was successfully encapsulated into lipid-core nanocapsules (LNCamb), a nanoformulation designed to deliver lipophilic drugs via diverse routes, including oral administration.
The LNCamb formulation was prepared using interfacial deposition of a pre-formed polymer. The organic phase, composed of poly(ε-caprolactone) (PCL), caprylic/capric triglyceride, sorbitan monostearate, and AMB dissolved in acetone, was injected into an aqueous polysorbate 80 solution under magnetic stirring. Subsequent removal of acetone and concentration of the suspension yielded a 10 mL aqueous dispersion of LNCamb. This optimized process ensured the stability and uniformity of the nanocapsules, with AMB effectively encapsulated within the lipid core.

Ambrisentan Chitosan-Coated LeciPlex: A Pulmonary Nanosystem for Enhanced Bioavailability

Eid H. M, et al. Journal of Pharmaceutical Sciences, 2024, 113(8), 2320-2330.

This study highlights the development of ambrisentan chitosan-coated LeciPlex (AMS-CTS-LPX) as a pulmonary nanosystem designed to enhance the therapeutic efficacy and bioavailability of ambrisentan. Utilizing a central composite design (CCD) and Design Expert® software, the researchers optimized the formulation through a single-step assembly process. The optimized AMS-CTS-LPX demonstrated remarkable properties, including an entrapment efficiency of 82.39%, a nanoscale particle size of 137.53 nm, and a high surface charge of +43.65 mV, ensuring stability and effective pulmonary delivery.
Pharmacokinetic analysis in a rat model revealed a 5.6-fold increase in the bioavailability of ambrisentan compared to the oral solution, suggesting significant improvements in drug absorption. The formulation exhibited a sustained release profile with 90.41% cumulative drug release over 8 hours. Additionally, in vivo histopathological studies confirmed the safety of intratracheal administration.

Custom Q&A

What is the molecular formula of Ambrisentan?

The molecular formula of Ambrisentan is C22H22N2O4.

What are some synonyms for Ambrisentan?

Some synonyms for Ambrisentan include Letairis, Volibris, LU-208075, and BSF 208075.

What is the IUPAC name of Ambrisentan?

The IUPAC name of Ambrisentan is (2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoic acid.

What is the CAS number of Ambrisentan?

The CAS number of Ambrisentan is 177036-94-1.

What is the InChIKey of Ambrisentan?

The InChIKey of Ambrisentan is OUJTZYPIHDYQMC-LJQANCHMSA-N.

What is the chemical structure of Ambrisentan?

The chemical structure of Ambrisentan is a diarylmethane.

What is the health hazard of Ambrisentan?

The reference does not provide information about the health hazard of Ambrisentan.

Who is the manufacturer of Ambrisentan?

The reference does not provide information about the manufacturer of Ambrisentan.

What is the date of creation of the Ambrisentan record?

The record of Ambrisentan was created on July 28, 2006.

What was the last modification date of the Ambrisentan record?

The last modification date of the Ambrisentan record is August 26, 2023.