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From high-throughput screening to lead compounds: Do you know what amazing twists and turns there are in this process?
The drug discovery process, from high-throughput screening (HTS) to the generation of lead compounds (Hit to Lead, H2L for short), is a road full of challenges and surprises. The main purpose of this phase is to evaluate small molecules from the screen in order to target promising lead compounds after limited optimization. This article will take you through each important step in the process and how they impact the success of the final drug.
Hit Confirmation
After potentially effective compounds are identified in high-throughput screening, the authenticity and validity of these "hits" must be confirmed. This process includes:
"Confirmatory testing is the retesting of relevant compounds against a selected target to ensure reproducible activity."
Further validation includes dose-response curves, orthogonal testing, secondary screening, and biophysical testing, all designed to ensure that the selected compound effectively binds to the target and performs in biological systems.
Hit Expansion
Once validation is complete, multiple compound clusters will be selected based on their properties. An ideal compound cluster should have:
"High affinity, selectivity, significant cell potency and appropriate drug similarity."
The goal of this stage is to generate new analogs by analyzing the relationship between similar structures to further promote the discovery of lead compounds.
Lead Optimization
After H2L, we entered the more critical pilot optimization stage. The main purpose of this process is to synthesize lead compounds with higher potency and reduce the risk of side effects and other adverse reactions.
"Lead optimization relies on understanding the structure-activity relationship (SAR) and performing corresponding chemical modifications."
This stage often involves experimental testing on animal models to evaluate the compound's potential for preclinical development.
Elements of success
In the drug discovery process, the key to success lies in effectiveness and innovation at each stage. As pointed out by the European Federation of Medicinal Chemistry and Chemical Biology (EFMC), efficient screening technology and best practices are important factors in promoting drug development.
"Best practices not only increase the probability of discovering new compounds, but also save time and costs."
As technology continues to evolve, future drug development may see more breakthrough progress, which also means there are unexpected surprises from the H2L process.
Future Outlook
As new technologies and methodologies emerge, we may see further improvements in efficiency and accuracy in the H2L phase. For drug developers, understanding and mastering this process will be the key to success.
So, what other surprising twists do you think will occur in this continuously developing field?
