Creative Biolabs has been working on the research of drug development for decades, having professional expertise and powerful technology platform. We can provide the best services for drug development covering Target ID and Validation, Hit Identification, Hit-to-Lead, Lead Optimization. In the process of lead optimization, we can make various schemes of safety pharmacology evaluation for your drug candidate, including safety pharmacology on cardiovascular function.
Safety pharmacology test is a very essential step in the process of drug development, which is performed to evaluate the potential adverse effects of a drug candidate prior to phase I human clinical trials. As a type of vital system in organism, the cardiovascular system function is necessary for maintaining normal life activity. Cardiovascular safety pharmacology core battery studies are carried out to investigate the potential undesirable pharmacodynamic effects of a drug candidate on cardiovascular system function, which a key procedure in drug development, approved by ICH S7A/S7B. Through this test, the safety profile of a potential new drug is obtained, which provides pharmacological data for further optimization of the candidate and the final selection of candidate suitable for clinical development. Currently, in vivo, in vitro, and/or ex vivo methods have been developed to assess the effects of new drug candidates on cardiovascular system function.
1. hERG Assays
Human ether-à-go-go related gene (hERG) encodes the K+ channel which mediates the myocardial membrane current IKr. It acts as the molecular of a wide range of drugs. Blocking the current IKr is associated with an increased risk of drug-induced severe arrhythmia with QT prolongation. Hence, it is required to detect the activity of hERG channel during cardiovascular safety pharmacology studies. Currently, several tests have been developed for detecting activity on IKr:
Fig.1 Concentration and time-dependence of IhERG inhibition by E-4031 and E-4031-17.1
2. Voltage Clamp Studies on Potassium Channels
Potassium channels play an important role in regulating various biological processes, including regulating electrical patterns of neurons and heart, neurotransmitters release, muscle contractility, hormone secretion, and signal transduction. Voltage clamp studies are performed to measure the function of individual potassium channels in heterologous cell systems or isolated ventricular myocytes.
3. Myocardial Action Potential Configuration
In addition to evaluating the effects of a compound on hERG channels, the effects of a compound on the overall myocardial action potential are also required in the safety pharmacology studies. Currently, the effect of a drug on myocardial action potential can be measured in in vitro myocardial tissue, usually using Purkinje fibers, papillary muscles, ventricular wedge, or the entire isolated heart.
Our professional experts have accumulated a lot of experience in the drug development, especially specialized in evaluating safety pharmacology of a new drug candidate and lead optimization. Aided by versatile techniques and high-quality in vitro models, Creative Biolabs is very confident in providing the best analytical service of cardiovascular safety pharmacology, helping you make an optimal selection of candidate suitable for clinical development. Please contact us to learn how we can be involved in your project.
Reference
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