Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.

By Derek Lowe

Posts tagged with "Drug Assays"

• Animal Testing

  Enough With the Mouse Behavioral Models?

  16 April, 2019

  This piece in STAT is well worth a read. The author, Adam Rosenberg of Rodin Therapeutics, is ready to ditch rodent-centric models for human CNS disease, and I can see where he’s coming from. I’ve often said that when I think back on my Alzheimer’s and schizophrenia drug discovery days (back when I was first… Read More

• Chemical Biology

  Making Some New Compounds, to Fit Some New Receptors

  12 April, 2019

  Here’s some medicinal chemistry combined with synthetic biology for you. Many people are used to thinking in terms of finding small-molecule probes for various cell targets, and those are valuable things. But what if you want to control a certain population of (for example) ion channels, but there aren’t any compounds that will do the… Read More

• Cancer

  Making and Measuring Multivalency

  9 April, 2019

  Here’s an unusual paper that’s studying receptor behavior on cell surfaces by use of atomic force microscopy. (Here’s the SI file, which is free to access). The authors took the marketed VEGF inhibitor vandetanib (VD6474) and attached it through linkers to the AFM tip, and then scanned around the surface of live human umbilical v… Read More

• Drug Assays

  Comparing Compound Collections

  8 April, 2019

  A common question – well, it should be a common question, anyway – is “How do I make sure that this compound collection is a useful one to screen?” There are alternative forms that come down to the same issues – if you’re putting together a new focused screening set, what should be in it?… Read More

• Analytical Chemistry

  A Close Look at Fragments

  3 April, 2019

  Here’s a look from the D. E. Shaw research team at fragment binding, and even if you don’t do fragment-based drug discovery, it’s worth a read. That’s because the mechanisms by which fragments bind to proteins are most likely the fundamental ones by which larger molecules bind as well; this is the reductionist look at… Read More

• Chemical Biology

  What Those Degraders Are Actually Doing

  12 March, 2019

  Since targeted protein degradation is such a hot topic these days, this paper (which adds to the results obtained by this one) should get some interest. It’s a report of a detailed look at the kinetic behavior of several bifunctional degraders – and there’s a lot of kinetic behavior to look at. That’s because you’re l… Read More

• Drug Assays

  Experiences With Phenotypic Screening?

  7 March, 2019

  Very little blogging time today, but I wanted to throw a question out to the readership instead. I’m at the Keystone conference on Phenotypic Drug Discovery, so here’s a relevant topic: what are your own experiences with phenotypic screening? Background for those outside the field: broadly speaking, you can sneak up on a drug by… Read More

• Biological News

  Targeting microRNAs

  26 February, 2019

  Medicinal chemists spend the vast majority of their time targeting proteins. Enzyme active sites, receptors, allosteric sites, interfacial sites – it’s one protein after another, to the point that you can mentally assume that your compounds are going to be hitting the familiar landscape of backbone amide bonds, pi-interacting tryptophan… Read More

• Drug Assays

  Virtual Screening – As Big As It Currently Gets

  11 February, 2019

  This new paper on “ultra-large” virtual screening is well worth a look in detail. We find a great many lead compounds in this business by random screening of compound libraries, and virtual screening is (as the name implies) the technique of doing this computationally instead of with hundreds (thousands) of sample plates and tireless ro… Read More

• Animal Testing

  A Toxicological Flag

  14 January, 2019

      Here’s a caution from a new paper out of Manchester. The group had been synthesizing inhibitors of PARG (poly-ADP ribose glycohydrolase), an enzyme involved in DNA repair. The general chemotype is shown at right, but there are a number of variations. That fluorine is a new addition, though. The corresponding cyclopropylmethyl se… Read More