tag:blogger.com,1999:blog-1136153439451224584.post7510991126172773417..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: Sometimes Your Compound SucksDr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-1136153439451224584.post-59979478965416954342012-04-19T23:49:43.995-07:002012-04-19T23:49:43.995-07:00J Med Chem has gone to shit over the years. Look a...J Med Chem has gone to shit over the years. Look at who is at the helm, they are self serving idiots. They still publish crap like this, crap full of aggregators and PAINS all the time, and crap that was sent in from companies like Schrodinger, who don't do any due diligence and who change the predictions after they find out the answers.<br /><br />Basically, if you are on the accepted list of scientists and you persist, you'll get your paper published. Because honestly, how much lower can you go? Some docking papers get sent to JCIM to die, but others basically die in J Med Chem. And everybody needs every paper to be accepted.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-55494274676869431072012-04-19T17:20:26.455-07:002012-04-19T17:20:26.455-07:00Actually, there is supplemental information, with ...Actually, there is supplemental information, with structures for all the fragments tested. It's linked on the ACS page. That said, yeah... no good.Annenoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-15267857369047949462012-04-19T15:34:12.067-07:002012-04-19T15:34:12.067-07:00" I’ve met the PI and I think she’s a first-r..." I’ve met the PI and I think she’s a first-rate scientist."<br /><br />I appreciate that, and I have often felt that way about scientists whom I have met.<br /><br />Then I read one of their papers, and the rubber meets the road.<br /><br />This is not the work of a first-rate scientist(s). This is crraap.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-87578894165510995832012-04-18T16:15:41.764-07:002012-04-18T16:15:41.764-07:00This was also highlighted here: http://pipeline.co...This was also highlighted here: http://pipeline.corante.com/archives/2012/04/18/how_do_these_things_get_published.php <br />I am not the only appalled at this paper.Dr. Teddy Zhttps://www.blogger.com/profile/07288045760981372367noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-79802800751058908062012-04-18T12:11:18.744-07:002012-04-18T12:11:18.744-07:00I do think it’s nice that more academics are using...I do think it’s nice that more academics are using and publishing on fragments, and while I may not be quite as “grouchy” as Teddy I do think he raises important points. One additional point I’d like to raise is that more experiments need to be done to demonstrate that the compounds (and possibly even the fragments themselves) are bona fide inhibitors. Small heterocycles, even with carboxylic acid moieties, have repeatedly been shown to form aggregates at high concentrations (see for example <a href="http://practicalfragments.blogspot.com/2010/01/pinning-fragments-on-pin1.html" rel="nofollow">here</a> and <a href="http://practicalfragments.blogspot.com/2010/04/getting-misled-by-nmr-iloe-artifacts.html" rel="nofollow">here</a>), which can overwhelm true positives in functional assays.<br /><br />According to the experimental section the researchers did not have detergent in their assay. Adding <a href="http://practicalfragments.blogspot.com/2009/08/avoiding-will-o-wisps-aggregation.html" rel="nofollow">detergent</a> is one of the most straightforward ways to prevent aggregation, so inhibitors found in the absence of detergent require further scrutiny. In this case, the fact that the compounds show steep Hill slopes is also consistent with aggregation. Although the compounds show some evidence of competition with both substrate and cofactor, in my opinion these experiments need to be done at more than two concentrations to truly determine their mode of inhibition.<br /><br />I don’t mean to pick on these folks – I’ve met the PI and I think she’s a first-rate scientist. Perhaps these are legitimate DHFR inhibitors. However, it’s all too easy to be misled, and I think everyone would be well-served to follow the advice of Chris Austin: “Every data point we generate is an artifact until proven otherwise.”Dan Erlansonhttps://www.blogger.com/profile/07927082337051189270noreply@blogger.com