Development of Beta-Blockers for Cardiovascular Diseases

Beta-adrenoceptor antagonists, commonly known as beta-blockers, are a class of drugs that selectively bind to beta-adrenergic receptors, effectively blocking the action of neurotransmitters on these receptors. Leveraging our team of professional scientists, Ace Therapeutics provides comprehensive preclinical drug development services to accelerate the discovery and optimization of novel beta-blockers.

The Role of Beta-Adrenoceptors in Cardiovascular Diseases

β-adrenergic receptors are located on the cell membranes of effector organs innervated by sympathetic postganglionic fibers. Overactivation of these receptors is closely associated with the pathogenesis of various cardiovascular diseases. For instance, overstimulation of β₁-receptors can elevate cardiac output, contributing to increased blood pressure. Additionally, overstimulation of β₁-receptors enhances the conduction velocity of cardiomyocytes, potentially triggering arrhythmias. In summary, β-adrenergic receptors play a vital role in the progression of cardiovascular diseases. By modulating the activity of β-adrenergic receptors, a wide range of cardiovascular diseases can be effectively prevented and treated, highlighting their importance as therapeutic targets.

Fig. 1 Molecular design of selective photoswitches targeting β₁-AR. (Duran-Corbera A, et al., 2022)

Discovery of Beta-Blockers

• Small Molecule Beta-Blockers
  We are committed to providing preclinical research services for innovative small molecule beta-blockers, including non-selective beta-blockers and selective β₁-blockers.
• Multi-targeted Drugs
  Developing multi-targeted drugs is a leading strategy in modern therapeutics. We can assist clients in designing and optimizing multi-targeted drugs, such as targeting beta-adrenoceptors and angiotensin receptor antagonists (ARBs) for the treatment of complex cardiovascular diseases.

In Vitro Pharmacodynamic Studies

• Receptor Binding Assay
  We utilize radioligand binding assays to determine the affinity (Ki value) of drug candidates for β-adrenergic receptor subtypes (β₁, β₂ or β₃), which allows us to assess drug selectivity and specificity for different receptor subtypes.
• cAMP Assay
  We can measure intracellular cAMP levels to evaluate the antagonistic effects of candidates of β-blockers. This method provides critical insights into drug-receptor interactions and downstream signaling pathways.
• Intracellular Calcium Measurement
  We employ fluorescent dyes or electrophysiological techniques to assess the effects of β₁-blockers on intracellular calcium ion concentrations, offering a detailed understanding of their impact on cellular function and signaling.
• Efficacy Evaluation on Cellular Models
  Using cell lines such as HEK293 or CHO cells expressing β-adrenergic receptors, we can evaluate the potency and efficacy of drug candidates and also explore the drug effects on cell proliferation, apoptosis, and key signaling pathways.

In Vivo Pharmacodynamic Studies

• Effects on Hypertension
  We provide customized animal models of hypertension, such as spontaneous hypertensive rats (SHR), to evaluate the antihypertensive effects of β-blockers.
• Effects on Heart Failure
  We offer customized animal models of heart failure, such as coronary artery ligation-induced heart failure models, to assess the effects of drug candidates on cardiac function and cardiac remodeling.
• Effects on Arrhythmias
  We develop customized animal models of arrhythmias to evaluate the anti-arrhythmic effects of drug candidates.

Ace Therapeutics, with experience in the field of cardiovascular disease, is dedicated to providing clients with drug discovery and development solutions to facilitate the development of novel beta-blockers. If you are interested in our services, please do not hesitate to contact us.

1.  Duran-Corbera, A.; et al. A Photoswitchable Ligand Targeting the β₁ -Adrenoceptor Enables Light-Control of the Cardiac Rhythm. Angew Chem Int Ed Engl. 2022, 61(30):e202203449.