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Industrial Liaison Group:
Tel: +44 (0) 1235 778797
E-mail: [email protected]
If you are an academic user of fragment screening, further information is available to help you access Xchem.
We have several fragment libraries freely available to our industrial users. All are available in DMSO at 100-500 mM concentrations. The fragments are in Echo-compatible source plates ready for rapid crystal soaking experiments. None of the compounds in our collection are bound by any IP.
Details regarding the libraries are outlined below.
DSPL is a poised fragment library to allow rapid, cheap follow-up synthesis to provide quick SAR data. "Poised" fragments contain at least one functional group which can be synthesised using a robust, well-characterised reaction. Reactions include amide couplings, Suzuki-type aryl-aryl couplings and reductive aminations. The library was designed by analysing all of commercially available fragment space for poised-ness and selecting a chemically diverse subset.
For one challenging target, the second bromodomain of PHIP, the first ever reported hits were obtained by XChem screening; two hits were poised and were followed up accordingly, yielding compounds with improved potency in the sub-100uM range and showing good ligand efficiency - and of course detailed structural data.
More detail on the design and utility of the library can be found in our publication:
O. B. Cox, K. Krojer, P. Collins, O. Monteiro, R. Talon, A. Bradley, O. Fedorov, J. Amin, B. D. Marsden, J. Spencer, F. von Delft, P. E. Brennan, A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain. Chem. Sci., 2016, 7, 2322-2330.
UPDATE - December 2017:
The original DSPL fragment library has been replaced by a second generation poised library: DSiP provided by the chemical supplier Enamine (www.enamine.net). It is also available to purchase in a screening format. The same criteria were applied for the design of this new library 2/3 of the fragments are different from the DSPL. For previous users, see below the files attached that will help you sort compounds (un)availability in the new DSiP set. One of the main advantage is that all the compounds are available to purchase with Enamine as well as closely related compounds for a quick SAR.
Although only available in DMSO, it is possible to request a copy of the library in a different solvent (e.g. ethylene glycol) to Enamine (expect a month leadtime for delivery).
For users that have done a screen using the original DSPL library and wanting to compare both DSPL and DSiP libraries, see documents below:
- Original DSPL library (xlsx)
- Spreadsheet showing which compounds from the DSPL library are in the new DSiP library and in which well of the 1536 plate (xlsx)
- Spreadsheet showing the compounds in both DSiP and DSPL (xlsx)
- Spreadsheet showing the compounds in DSiP but not in DSPL (xlsx)
- Spreadsheet showing the compounds in DSPL but not in DSiP (xlsx)
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