Creative Biolabs is dedicated to assisting our global clients on their cutting-edge drug discovery and development process by providing an integrated service portfolio of in vitro toxicity assays. Particularly, we proudly present our exclusive technical platform for cardiotoxicity detection.
Drug-induced cardiotoxicity is the leading cause of both drug development failures and market withdraw or restriction. Compounds that exert cardiovascular toxicity, no matter acute or subtle effect, can lead to severe adverse consequences, such as arrhythmia, myocardium structural damage, and even sudden death. Therefore, a comprehensive survey of cardiac safety represents a high priority for IND submissions as well as a crucial step to prevent later stage failures.
Aided by high-content analysis and advanced in silico technologies, Creative Biolabs has established multiple high throughput cardiotoxicity tests for screening and identifying compounds or pathways that may potentially interfere with cardiac physiology or functions.
Ion Channel Assays
The heart is a spontaneously beating organ mediated by complex electric activities. Many drug components may disturb the normal cardiac rhythm by altering the function of ion channels, thus result in QT syndrome, ventricular arrhythmia, and sudden death. Creative Biolabs offers diverse GLP ion channel assays by manual patch clamp technology. We also conduct further dose formulation analysis (DFA) to obtain accurate IC50 values for risk evaluation and IND-enabling.
Ion channels available for assessment including but not limited to:
In addition, we are also capable of investigating multiple ion channel effects (MICE) by simultaneously analyzing changes in all major ion channels in a single assay, thus providing more comprehensive cardiotoxicity profiles for effective decision-making during early preclinical development.
The human ether-a-go-go-related gene (hERG), which encode the inward rectifying voltage-gated potassium channel (IKr), plays a key role in cardiac repolarization. hERG inhibition or blockage can cause QT interval prolongation, which might lead to various fatal risks. To assess hERG inhibition potential of preclinical drugs becomes an imperative standard procedure in the cardiac safety evaluation. Our scientists have extensive experience in conducting hERG screening using manual or automatic patch clamp system. The test can be performed in the presence or absence of serum proteins.
Cardiac Action Potential Assay
Cardiac action potential duration (APD) assay is commonly recommended by regulatory agencies for IND submission. Creative Biolabs has successfully developed a highly predictive cellular model by human iPSC-derived cardiomyocytes (SC-hCMs). Through manual patch clamp recordings in isolated SC-hCMs, drug-induced action potential prolongation and arrhythmia can be obtained. Alternative custom human cardiomyocyte assays are also available upon request.
In Silico 3D-based Structural Model
Our unique 3D-based structural model is based on tri-culture of cardiomyocytes (SC-hMCs) and non-cardiomyocytes (endothelial and fibroblast cells), to mimic in situ human heart tissue. This so-called “microtissue” can spontaneously beat and are amenable for long-term culture, hence offering an excellent tissue-based system for cardiotoxicity investigation. Combined with high content screening and in silico software, our 3D structural model empowers researchers to evaluate general structural cardiotoxicity, calcium dyshomeostasis, and morphological changes (e.g. hypertrophy).
Detecting cardiotoxicity potential in early lead optimization stage will effectively enhance future success rate and reduce time and cost expense. As your trustworthy and reliable research partner, Creative Biolabs guarantees consistent, high-quality cardiotoxicity profiles with the considerate flexibility to adapt different protocols to address specific custom issues.
For more detailed information, please feel free to contact us or directly sent us an inquiry.
For Research Use Only.
