Development of Angiotensin Converting Enzyme Inhibitors for Cardiovascular Diseases

Angiotensin converting enzyme (ACE) inhibitors exhibit potent antihypertensive effects by delaying and reversing ventricular remodeling, preventing myocardial hypertrophy, and improving vascular endothelial and cardiac function. Ace Therapeutics is a trusted partner dedicated to providing R&D services for the development of innovative therapies for cardiovascular diseases. We provide comprehensive drug discovery and preclinical pharmacodynamic evaluation services to accelerate the discovery and optimization of novel ACE inhibitors.

The Role of Angiotensin Converting Enzyme in Cardiovascular Diseases

Angiotensin converting enzyme (ACE) is a key regulator in the onset and progression of cardiovascular diseases. It turns angiotensin I into the powerful vasoconstrictor angiotensin II, while simultaneously degrading the vasodilator bradykinin. This dual action drives hypertension, heart failure, atherosclerosis, and other cardiovascular diseases. Blocking ACE halts these cascades, making ACE inhibitors the first-line therapies for managing hypertension and related diseases.

Fig. 1 Neurohumoral pathways and pharmacological targets in heart failure. (Mascolo A, et al., 2022)

Discovery of ACE Inhibitors

• Small Molecule ACE Inhibitors
  We assist our clients in developing innovative small molecule ACE inhibitors and provide end-to-end preclinical R&D services, including high-throughput screening, lead compound optimization, and efficacy evaluation of candidate small-molecule drugs.
• Dual-Targeted ACE Inhibitors
  Development of dual inhibitors, such as dual ACE/NEP inhibitors, is a growing trend in cardiovascular drug research. We can design and optimize dual inhibitors that target both ACE and other targets, tailored to meet the unique needs of our clients.

In Vitro Pharmacodynamic Studies

• ACE Inhibitory Activity Assay
  Using fluorescent substrates or colorimetric assays, we determine the inhibitory activity (IC₅₀ value) of drug candidates against ACE and evaluate their selectivity for different ACE subtypes.
• In Vitro Evaluation in ACE-Expressing Cell Lines
  We employ ACE-expressing endothelial and smooth-muscle cell lines to provide in vitro efficacy data, while profiling drug effects on proliferation, apoptosis, and critical signaling cascades.

In Vivo Pharmacodynamic Studies

• Effects on Hypertension
  Providing customized animal models of hypertension, such as spontaneously hypertensive rats (SHR), we can conduct in vivo evaluation studies for our clients to assess the antihypertensive effects of drug candidates.
• Effects on Heart Failure
  We provide specialized animal models, such as coronary artery ligation-induced heart failure models, to assess the effects of drugs on cardiac function and remodeling.

At Ace Therapeutics, we specialize in comprehensive preclinical services that accelerate every phase of ACE inhibitor development. If you are interested in our services, please do not hesitate to contact us.

1. Mascolo, A.; et al. Current and future therapeutic perspective in chronic heart failure. Pharmacol Res. 2022, 175:106035.