XChem

Fragment-based screening is now well-established as a powerful approach to early drug (“lead”) discovery. Of the many suitable biophysical techniques, X-ray crystallography was one of the first to be used, and is the most directly informative (reference); however, the experimental overheads have historically been too high for it to be widely used for primary screening. At Diamond beamline I04-1, the full X-ray screening experiment has now been implemented as a highly streamlined process, allowing up to 500 crystals to be soaked and harvested in a day, and collected in 24 hours beamtime. The process covers soaking, harvesting, automatic data collection, and data analysis; and fragment libraries are available, or users can bring their own. Since April 2015, the XChem facility has been available to users with dedicated weekly beamtime, and is now part of the MX User Programme. Users can use in-house fragment libraries or bring their own. As a world-wide first facility, we welcome international proposals. The future focus is on exploring how best to harness the technique to proceed rapidly to potent compounds. Since 2015 more than 20 proteins have been screened and over 800 hits identified.