tag:blogger.com,1999:blog-1136153439451224584.post2831649757371186001..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: PAINS in C&ENDr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger6125tag:blogger.com,1999:blog-1136153439451224584.post-88805825107318076452014-09-03T04:37:35.199-07:002014-09-03T04:37:35.199-07:00A few specific examples for Q.2.
% PAINS
GPHR (Mi...A few specific examples for Q.2.<br /><br />% PAINS<br />GPHR (Minnesota) Library: 5.5% (primarily vendor libraries)<br />Three small (<50k), speciality libraries from Chembridge: 2.4, 4.3, 1.9 %<br /><br />As of late last year eMolecules had ~6% PAINS.<br /><br />Dahlin, J. L.; Walters, M. A. The essential roles of chemistry in high-throughput screening triage. Future Med. Chem. 2014, 6, 1265-1290.<br /><br />Just out of curiosity...<br />%REOS (These values may not be as bad as they look since nitros, etc. are flagged by the REOS filters.)<br />GPHR (Minnesota) Library: 28.3%<br />Three libraries (same as above) from Chembridge: 6.3, 11.8, 6.2<br /><br />Using filters as implemented in Canvas (Schrodinger).<br /><br />The PAINS content will vary from collection to collection but, ss Jonathan points out, "trust, but verify." Mikehttp://htspains.comnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-76878159474626019782014-09-02T22:22:07.428-07:002014-09-02T22:22:07.428-07:00HI Pete
See Table 7 of the PAINS paper.
That was...HI Pete<br /><br />See Table 7 of the PAINS paper.<br /><br />That was from 2009 catalogs but a check minutes ago on a 2014 catalogue gives a similar value (9%) for the same vendor 5 years apart. So these will definitely turn up in hit sets from vendor-supplied compounds.Jonathannoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-22619038636796244492014-09-02T17:47:01.973-07:002014-09-02T17:47:01.973-07:00Can you support the assertion that, "Commerci...Can you support the assertion that, "Commercial libraries tend to have 5-12% PAINS"?Peter Kennyhttps://www.blogger.com/profile/12180360326821860667noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-17607698979060206562014-09-02T06:03:00.900-07:002014-09-02T06:03:00.900-07:00That is so great. Thanks Jonathan. I will study yo...That is so great. Thanks Jonathan. I will study your interesting papers in more details...Andersnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-35842228658151284052014-09-01T21:11:28.198-07:002014-09-01T21:11:28.198-07:00While not wanting to self-cite, see this url and t...While not wanting to self-cite, see this url and these refs to get a good idea of recognizing likely PAINS:<br /><br />https://www.collaborativedrug.com/buzz/2010/03/08/guest-blog-dr-jonathan-baell/<br /><br />Baell JB. Observations on Screening-Based Research and Some Concerning Trends in the Literature. Future Med. Chem. 2 (2010) 1529–1546<br /><br />Baell JB & Holloway GA. New substructure filters for removal of pan assay interference compounds [PAINS] from screening libraries and for their exclusion in bioassays. J. Med. Chem. 53 (2010) 2719-2740<br /><br />Baell JB. Redox active nuisance screening compounds and their classification. Drug Discov. Today 16, 840-841 (2011)<br /><br />Commercial libraries tend to have 5-12% PAINS. Usually not removed. But not a big deal if you are aware....always be wary of any hit...it has to prove itself right and not the other way around.<br />Jonathannoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-83435342352641660872014-09-01T12:59:20.168-07:002014-09-01T12:59:20.168-07:00Hi. 2 Qs for the PAIN experts:
1. Is there a "...Hi. 2 Qs for the PAIN experts:<br />1. Is there a "complete/near-complete" list of pains found in literature somewhere (blogs/papers). Or maybe you can point to a comprehensive one. It would be a useful tool to hold future hits and libraries up against.<br /><br />2. Should one expect/fear pains in commercial libraries (eg Maybridge). I know aggregators are hard to predict, but can i count on that they have removed H2O2 generators, Michael acceptors, S-S creating compounds?<br /><br />Great blog btw.Andersnoreply@blogger.com