Application of High-throughput Drug Screening in New Drug Development

SHIRLEY, N.Y. - Dec. 12, 2021 - PRLog -- The principle of high-throughput drug screening is that drugs mostly re-adjust the patient's physiological state by specifically acting on target proteins (receptors, enzymes, ion channels, etc.). High-throughput screening (HTS), using microplates containing compounds and cells as carriers, is a method for screening drug candidates that interact with a target protein from a sample library.

1 The basic process of high-throughput drug screening and development of new drugs

Traditional pharmacological research generally firstly studies drug's object effects and then studies the mechanism of action. In contrast, since the result obtained by high-throughput screening is at the molecular or cellular level, in most cases, it can only reflect the mechanism of the sample's action and fails to fully prove its preventive effect on a certain disease, which is an important difference between high-throughput screening and traditional screening methods.

1.1Primary screening and secondary screening

Primary screening and secondary screening refer to screening samples at the molecular or cellular level to testify a sample's pharmacological activity (or affinity) for the target.

1.2In-depth screening

On the basis of primary screening and secondary screening, the obtained samples are further screened by using different but related molecular and cellular models from the preliminary screening to prove the selectivity, cytotoxicity, and other properties.

1.3Confirmatory screening

More in-depth and extensive research can be conducted on the lead compounds obtained by in-depth screening or the compounds with the best activity after optimization, including screening of their pharmacological effects, drug metabolism processes, toxicity, and other properties to determine their development potential.

2 The transformation of high-throughput drug screening technology to drug development strategies

2.1 Changes in screening strategy
The application of high-throughput drug screening (https://www.solutions.bocsci.com/high-throughput-screenin...) technology has revolutionized drug discovery process. Since the screening method is based on the molecular and cellular level, there are bound to be many problems to be solved in analyzing the therapeutic effects of drugs.

2.2 Directed screening
The application of combinatorial chemistry technology has brought about tremendous changes in the structure optimization and transformation of active compounds and greatly improved the efficiency.

2.3 Approach to molecular design
There are two main ways of applying computer-aided drug design (https://www.solutions.bocsci.com/computational-chemistry.htm) (CADD) in the discovery process of new drugs. The first method is to establish a three-dimensional active site structure by simulating the structure of the drug target, and then design the molecular structure of the compound that can be combined with the active site, and at last use a synthetic method to obtain the compound. The second method, computer screening, emerged after years of development. This method is based on the active compound or the effective medicinal chemical structure that is already known, referring to the structural characteristics of the drug target.