Fragment-Based Drug Discovery: Difference between revisions

The first step of FBDD is to expose the potential drug target to a large number of small molecular fragments. This is usually done with a method known as high-throughput screening. [http://www.http://en.wikipedia.org/wiki/High-throughput_screening High-throughput screening] (HTS) is the process of using robotics to perform a large number of chemical tests. HTS is used to quickly identify fragments that have affinity for the target which are then analyzed to understand why they have affinity.

<scene name='Sandbox_reserved_394/Compound_1/7'>Two fragments</scene> were found to have moderate affinity for Bcl-xl. <scene name='Sandbox_reserved_394/Compound_1/2'>Compound 1</scene> is a fluorobiphenylcarboxylic acid. It occupies <scene name='Sandbox_reserved_394/Binding_site_1/1'>binding site 1</scene> of Bcl-xl. The fluorobiphenyl portion of compound 1 is very hydrophobic. Therefore, Bcl-xl forms a <scene name='Sandbox_reserved_394/Compound_1/4'>"hydrophobic pocket"</scene> around the fluorobiphenyl system. The <scene name='Sandbox_reserved_394/Compound_1/5'>carboxyilic acid portion of compound 1 binds near Gly 142</scene> of Bcl-xl.

<scene name='Sandbox_reserved_394/Compound_1/3'>Compound 2</scene> is a napthalene-based alcohol which occupies <scene name='Sandbox_reserved_394/Binding_site_2/1'>binding site 2</scene>. This particular fragment also is involved with hydrophobic interactions with Bcl-xl, although they are not as strong as in the case of compound 1.