Cardiac safety evaluation is an important factor that must be investigated before various new drugs enter clinical trials, and it is also one of the most important and difficult links in the early clinical research of innovative drugs. The QT interval of the heart refers to the period from the beginning of the QRS complex to the end of the T wave, including the process of ventricular depolarization and repolarization. The QT interval is considered to be one of the key indicators for the safety evaluation of new drugs. In cardiomyocytes, the potassium channel encoded by hERG (human Ether-a-go-go Related Gene) mediates a delayed rectifier potassium current (IKr), and IKr inhibition is an important mechanism by which drugs lead to prolongation of the QT interval. hERG can be inhibited by compounds with diversified structures. The loss of its function or drug inhibition will affect the repolarization process of cardiac action potentials and cause the QT interval to prolong. At the same time, it can induce torsade de pointes ventricular tachycardia and cause arrhythmia.
With the continuous deepening of research, the safety evaluation technology of hERG inhibition has become more mature. At present, there are many mature evaluation methods on the market, such as Automated Patch-Clamp technology (Automated Patch-Clamp), traditional patch-clamp technology ( ConventionalPatch-Clamp) and FluxORTM Thallium Assay.
The basic principle of patch clamp (Patch Clamp) is to use a glass electrode with a tip diameter of 0.5-1um to be attached to the surface of the cell membrane. The electrode tip and the cell membrane are tightly sealed by suction through negative pressure, so that the cell membrane is connected to the center of the electrode tip. The patch is electrically insulated from its surroundings, and the membrane potential (clamp) is fixed on this basis, and then the current of one or several ion channels on the cell membrane with an area of only a few square microns under the electrode tip is recorded. Thus, the electrophysiological technology is improved to the molecular level of recording and studying individual proteins.
Patch clamp technology has been widely used in myocardial ion channel research related to drug action, the study of the relationship between single cell morphology and function, drug action mechanism, cardiovascular pharmacological research, innovative drug research and high-throughput screening.
Medicilon introduced the HEKA Patch Clamp System, which is an integrated amplifier and digital-to-analog converter. It can be combined with manual operation through software to achieve a more accurate degree than full automatic, which will greatly enhance Medicilon Western in vitro drug safety evaluation service.
The Medicilon Drug Safety Evaluation Center is composed of a group of experienced professional scientific research teams. It has established a drug safety evaluation system that meets international standards. The experimental research follows the guidelines of ICH, CFDA, FDA and OECD, and can provide high-quality data and fast With the drug preclinical safety evaluation service in the research cycle, Medicilon helps customers shorten the experimental time and reduce the cost of new drug research and development through cost-control and efficient services. Since 2012, Medicilon has successfully helped nearly 50 customers submit application materials that meet the requirements of new drug registration to CFDA, FDA and TGA, and has accepted and passed more than 100 verifications.
hERG test-preclinical cardiac safety evaluation
hERG Assay – Drug Preclinical Cardiac Safety Assessment
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