Drug Screening

Background introduction

Drug screening is a step in the modern drug development process to test and obtain specific physiologically active compounds. It refers to the process of selecting compounds with higher activity for a specific target from a large number of compounds or new compounds through standardized experimental methods. It is a necessary process for the development of clinical new drugs.

 

With the emergence of high-throughput methods of genomics and synthetic chemistry, drug screeners are faced with more and more new targets or potential effective ingredients. High-throughput screening has emerged in this context. A high-throughput drug screening system includes micro and semi-micro pharmacological experiment models, sample library management systems, automated experimental operating systems, high-sensitivity detection systems, and data acquisition and processing systems. The operation of these systems ensures that the screening system can be operated in parallel Search for a large number of candidate compounds.

 

AMTK provides an automated experimental operating system for high-throughput drug screening systems, and provides solutions for screening models at the biochemical and cellular levels of various pharmaceutical companies.

 

Case Studies

In the field of new drug screening, CISBIO BIOASSAYS's patented technology HTRF (Homogeneous Time-resolved Fluorescence) is widely used in major pharmaceutical companies, drug research institutes and new drug screening centers around the world. HTRF, in short, is a no-wash ELISA, which combines the two technologies of Fret (Fluorescence Resonance Energy Transfer) and TRF (Time-resolved Fluorescence). It only needs to add liquid and incubate. With the three steps of plate reading, cumbersome and variable washing steps are eliminated, not only the operation is simple, but the result is more stable and reliable.

 

In recent years, PD-1/PD-L1 immune checkpoint inhibitors, as a new type of cancer immunotherapy, have achieved amazing results in a variety of cancer treatments. The case we selected is the use of HTRF technology to screen inhibitors of PD-1/PD-L1, and the experimental principle is shown in Figure 1. PD-L1 and PD1 are fused with tag proteins TAG1 and TAG2, respectively, which are recognized by their respective antibodies, ANTI-TAG1 and ANTI-TAG2. Since the antibody is labeled with the donor fluorescent dye EU of HTRF and the acceptor fluorescent dye XL665, when PD-L1 and PD1 are close and combined, the fluorescence resonance emitted by EU is transferred to XL665, causing XL665 to emit fluorescence, which is detected.

 

 

Figure 1

The experimental principle of screening PD1/PD-L1 inhibitors using HTRF technology

 

When the PD-1/PD-L1 inhibitor is present, it will hinder the binding of TAG1-PD-L1 protein to TAG2-PD-1, thereby affecting the intensity of the fluorescent signal of XL665

 

Screening experiment steps

Figure 2

PD1/PD-L1 inhibitor screening experimental procedures

 

Automation solution

Develop an automation plan according to the experimental steps, the instrument models are as follows:

 

  

AMTK LH-1406 multifunctional liquid handling workstation deck layout

 

Analysis of results

Comparison of IC50 between automatic liquidhandler and manual operation

Analysis of the consistency between automatic liquidworkstationand manual operation

 

 

 

 

Conclusion: AMTK LH-1406 laboratory automationrobothas realized the complete automation of the operation process, and the performance indicators have reached the requirements.

 


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