Hit to lead

Hit to Lead (H2L) is a process in Drug Discovery and Pharmacology that involves the identification of active, but chemically simple compounds, and their subsequent refinement into more potent and selective chemical entities. This process is a critical step in the development of new Medicinal Drugs.

Overview

The Hit to Lead process begins with the identification of a 'hit', a compound that demonstrates some level of activity against a chosen Biological Target. This hit is typically identified through High-Throughput Screening (HTS) of large libraries of compounds. Once a hit has been identified, it is then optimized through a process of Medicinal Chemistry to improve its potency, selectivity, and pharmacokinetic properties. This optimized compound is known as a 'lead'.

Hit Identification

Hit identification is the first step in the Hit to Lead process. This involves the screening of large libraries of compounds against a chosen biological target. The aim of this step is to identify compounds that show some level of activity against the target. This is typically achieved through the use of High-Throughput Screening (HTS), a process that allows for the rapid testing of large numbers of compounds.

Lead Optimization

Once a hit has been identified, it is then optimized to improve its potency, selectivity, and pharmacokinetic properties. This is achieved through a process of Medicinal Chemistry, which involves the systematic modification of the hit compound's chemical structure. The aim of this process is to produce a 'lead' compound that is suitable for further development.

Challenges

The Hit to Lead process is not without its challenges. One of the main challenges is the need to balance potency and selectivity with acceptable pharmacokinetic properties. This often requires a process of iterative design and testing, which can be time-consuming and costly. Additionally, the process is often complicated by the need to consider potential Toxicity and Side Effects of the lead compound.

See Also

• Drug Discovery
• High-Throughput Screening
• Medicinal Chemistry
• Pharmacokinetics
• Toxicology