Development of VDCC Blockers for Cardiovascular Diseases

Voltage-dependent calcium channels (VDCCs) are critical regulators of key physiological processes, including nerve conduction, muscle contraction, and synaptic transmission. Ace Therapeutics supports the essential research of clients and advance the development of VDCC blockers.

The Role of VDCC in Cardiovascular Diseases

VDCCs are a class of ion channel proteins, mainly found in cardiomyocytes and vascular smooth muscle cells, that mediate the plateau phase of the action potential and regulate myocardial contractility and vascular tone. Abnormal activation of L-type calcium channels may lead to cardiovascular diseases such as hypertension, arrhythmia, myocardial infarction and heart failure.

Fig. 1 Roles of L- and T-type calcium channels in the heart. (Kushner J, et al., 2019)

Current Status of VDCC Blocker Development

Calcium channel blockers act to dilate blood vessels, reduce myocardial contractility and slow heart rate by inhibiting the entry of calcium ions into smooth muscle cells, cardiomyocytes and the cardiac conduction system. VDCC blockers are primarily used to treat cardiovascular diseases, including hypertension, angina, and arrhythmias.

VDCC Blockers in Development or Approved for the Treatment of Cardiovascular Diseases

Discovery of VDCC Blockers

Leveraging our advanced technology platform, we provide a wide range of services to support the development of diverse VDCC blockers, ensuring innovative and effective therapeutic solutions for cardiovascular diseases.

• Small Molecule VDCC Blockers
  We assist our clients in developing highly selective and efficient small molecule calcium channel blockers. These compounds can target specific calcium channels or act on multiple channels simultaneously, offering versatile therapeutic options for complex cardiovascular conditions.

In Vitro Pharmacodynamic Studies

• Electrophysiological Measurement of Ion Channels
  Using the patch-clamp technique, we measure the effects of test drugs on calcium channels, including IC₅₀ values and channel open probability. This method provides precise and detailed insights into drug efficacy and mechanism of action.
• Pharmacodynamic Studies on Cellular Models
  We conduct cardiomyocyte experiments to evaluate the impact of test drugs on myocardial contraction and cardiac action potentials, with a focus on L-type VDCCs. These studies help elucidate the therapeutic potential of calcium channel blockers in cardiovascular function.

In Vivo Pharmacodynamic Studies

• Effects on Hypertension
  We choose animal models such as spontaneously hypertensive rats (SHR) to monitor the antihypertensive effects of the test drugs by invasive blood pressure measurement.
• Effects on Cardiac Function
  We perform retrograde heart perfusion experiments on isolated hearts to assess cardiac function parameters, including cardiac contractility and heart rate. This model offers valuable insights into the effects of test drugs on overall cardiac performance.

Ace Therapeutics, with the longstanding experience in the field of cardiovascular disease, is able to provide clients with drug discovery solutions to facilitate the development of novel VDCC blockers. If you are interested in our services, please do not hesitate to contact us.

1. Kushner, J.; et al. Roles and Regulation of Voltage-gated Calcium Channels in Arrhythmias. J Innov Card Rhythm Manag. 2019, 10(10):3874-3880.