Decreasing the high attrition rate in the drug discovery and development process is a primary goal of the pharmaceutical industry. The establishment of drug safety evaluation and screening model is helpful to understand the safety of drug candidates, reduce the high loss rate, and achieve the balance between drug efficacy and potential adverse reactions.
It has been estimated that about 75% of all adverse drug reactions (ADRs) are dose-dependent and can be predicted on the basis of the pharmacology profiles of the candi-date compound (known as type A ADRs). The A ADRs can be classified into primary or secondary effects. Primary effects relate to the action of the compound at its intended target, whereas secondary effects are due to interactions with targets other than the primary target (that is, off-target interactions). The off-target effects tend to lead to ADRs. Therefore, in the early stage of drug development, in vitro safety pharmacology profiling of drug candidates is beneficial to reduce ADRs in clinical studies. At the same time, identifying off-target tendencies in the early stages of drug development can also help develop strategies to improve drug candidates.
An unexpected off-target hit might cause undesirable adverse effects or lead to discontinuation of drug development. And in vitro pharmacologic safety analysis can detect adverse drug reactions, predict potential drug risks and evaluate drug safety range. Based on the 44 early drug safety targets recommended by AstraZeneca, GlaxoSmithKline, Novartis and Pfizer to detect off-target effects, we added another 46 important targets associated with adverse effects related to the central nervous system, cardiovascular system, metabolism, immunity, etc. It has become a screening model for the safety evaluation of 90 targets. The 90 Safety Panel provides data for PCC optimization, identifies off-target effects, facilitates drug selection, and evaluates and improves ADRs of PCC.
The safety of the compound is evaluated by evaluating the agonistic or inhibitory effect of the compound on the target by the method of functional activity screening, which provides a reference for the later research of the compound, that enable clients to utilize fit-for-purpose panels for quick and accurate evaluation, prediction and mitigation of potential risks from off-target related adverse drug reactions (ADRs), to help identify unsafe compounds earlier and design/select better drug candidates with increased probabilities of becoming marketed drugs.
