/home/corante/public_html/pipeline/ en-us derek-lowe@sbcglobal.net 2008-05-23T07:18:23-05:00 hourly 1 2000-01-01T12:00+00:00 http://pipeline.corante.com/archives/2008/05/23/up_close_and_personal.php Something that’s come up in the last few posts around here is the way that we chemists think about the insides of enzymes. It’s a tricky subject, because when you picture things on that scale, the intuition you have for... 73330@/home/corante/public_html/pipeline/ In Silico 2008-05-23T07:18:23-05:00 http://pipeline.corante.com/archives/2008/05/01/o_pioneers.php Drug Discovery Today has the first part of an article on the history of the molecular modeling field, this one covering about 1960 to 1990. It’s a for-the-record document, since as time goes on it’ll be increasingly hard to unscramble... 73268@/home/corante/public_html/pipeline/ In Silico 2008-05-01T07:26:00-05:00 http://pipeline.corante.com/archives/2008/03/27/start_small_start_right.php There’s an excellent paper in the most recent issue of Chemistry and Biology that illustrates some of what fragment-based drug discovery is all about. The authors (the van Aalten group at Dundee) are looking at a known inhibitor of the... 73187@/home/corante/public_html/pipeline/ In Silico 2008-03-27T07:30:02-05:00 http://pipeline.corante.com/archives/2008/03/05/smaller_wetter_harder_to_work_with.php There’s an interesting article coming out in J. Med. Chem. on antibiotic compounds, which highlights something that’s pretty clear if you spend some time looking at the drugs in that area. We make a big deal (or have made one... 73140@/home/corante/public_html/pipeline/ Infectious Diseases 2008-03-05T08:14:24-05:00 http://pipeline.corante.com/archives/2007/04/22/melting_keys_and_squishy_locks.php Pretty much the only thing that an interested lay person has heard about ligand binding is the "lock and key" metaphor. I'm not saying that you could walk down the sidewalk getting nods of recognition with it, but if someone's... 72244@/home/corante/public_html/pipeline/ Metaphors, Good and Bad 2007-04-22T20:19:20-05:00 http://pipeline.corante.com/archives/2007/03/12/no_shortcuts.php I wanted to link tonight to the "Milkshake Manifesto" over at OrgPrep Daily. It's a set of rules for med-chem, and looking them over, I agree with them pretty much across the board. There's a general theme in them of... 72116@/home/corante/public_html/pipeline/ Drug Assays 2007-03-12T20:01:51-05:00 http://pipeline.corante.com/archives/2007/02/27/wrong_but_still_convincing.php SciTheory has a post, complete with links to the relevant articles in Science, etc., on a recent batch of trouble in structural biology. Geoffrey Chang and his group at Scripps have been working on the structures of transporter proteins, which... 72079@/home/corante/public_html/pipeline/ In Silico 2007-02-27T14:41:23-05:00 http://pipeline.corante.com/archives/2006/12/14/love_and_anger.php Glenn Reynolds gave the pharma industry a much-appreciated thank-you card over at Instapundit: Only a moron would want to live in a society where people are ashamed to work for drug companies. And yet, I'm not surprised to see that... 70563@/home/corante/public_html/pipeline/ Why Everyone Loves Us 2006-12-14T15:06:47-05:00 http://pipeline.corante.com/archives/2006/09/11/enzymes_do_whatever_they_want_to.php It's been a while since I wrote about the neuraminidase inhibitors (Tamiflu and Relenza, oseltamavir and zanamivir). As we start to head into fall, though, I'm sure that avian flu will invade the headlines again, if nothing else (and I... 65315@/home/corante/public_html/pipeline/ In Silico 2006-09-11T19:29:47-05:00 http://pipeline.corante.com/archives/2006/03/23/crystals_of_doubt.php Here's a limits-to-knowledge post for you. On Wednesday, when I was cranking out a batch of an intermediate we're using these days, I needed to separate two fairly closely related compounds (which I'll call A and B) from each other.... 54027@/home/corante/public_html/pipeline/ In Silico 2006-03-23T22:45:09-05:00 http://pipeline.corante.com/archives/2005/11/01/molecular_modeling_cage_match.php I mentioned an interesting paper that's coming out in the Journal of Medicinal Chemistry on molecular modeling. It's a long one from a large group of people scattered across GlaxoSmithKline's worldwide research facilities, entitled "A Critical Assessment of Docking Programs... 37628@/home/corante/public_html/pipeline/ In Silico 2005-11-01T22:19:35-05:00 http://pipeline.corante.com/archives/2005/09/29/the_hazards_of_molecular_modeling.php A comment to the last post really gave me the shivers: "I like to think of modelling as the "silent killer". It is easy to rely on it for quick answers, and easy to forget that there is no substitute... 36673@/home/corante/public_html/pipeline/ In Silico 2005-09-29T23:15:14-05:00 http://pipeline.corante.com/archives/2005/09/28/clamping_down_or_loosening_up.php We medicinal chemists spend our days trying to make small molecules that bind to targets in living systems. Almost all of those targets are proteins of one sort or another, and most of them have binding pockets already built into... 36634@/home/corante/public_html/pipeline/ In Silico 2005-09-28T20:32:27-05:00 http://pipeline.corante.com/archives/2005/09/06/crossing_your_fingers_authoritatively.php I recall a project earlier in my career where we'd all been beating on the same molecular series for quite a while. Many regions of the molecule had been explored, and my urge was often to leave the reservation. I... 11295@/home/corante/public_html/pipeline/ Who Discovers and Why 2005-09-06T07:39:54-05:00 http://pipeline.corante.com/archives/2004/08/17/kinases_and_their_komplications.php I'm going to take off from another comment, this one from Ron, who asks (in reference to the post two days ago): "would it not be fair to say that cellular biochemistry gets even more complicated the more we learn... 11021@/home/corante/public_html/pipeline/ In Silico 2004-08-17T21:53:43-05:00