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"

• 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

• Chemical Biology

  Come One, Come All to These Kinases

  11 January, 2019

  Why do some proteins in a family prove very hard to target, while others bind a whole list of inhibitors? This paper takes a look at a particularly dramatic example in the kinase field. That’s a good place for studying such things, since there are a lot of kinases out there, and a lot of… Read More

• Analytical Chemistry

  More Than One, And Maybe More Than That

  7 January, 2019

  Every so often, we medicinal chemists need reminding that those beautiful X-ray crystallography structures of our ligands bound to target proteins are. . .not quite what we tend to think they are. Here’s a post I did on that a while back, and this new paper quantifies one of the issues. You see, what you… Read More

• Analytical Chemistry

  The Sartan Contamination Story

  4 January, 2019

  There’s a chemical contamination story in the generic drug industry that just isn’t going away. Late last summer, some lots of valsartan were recalled due to detection of N-nitrosodimethylamine (NDMA), and the problem has just continued since then. We’ll get into the chemistry of this problem in a minute, but first off, looking at… Read More

• Cancer

  Bromopyruvate Revealed

  14 November, 2018

  3-bromopyruvate is an interesting and controversial compound. It’s been reported to be an active chemotherapy agent, apparently acting via covalent inhibition of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequent metabolic effects via loss of pyruvate itself. Several years ago, you could come across numerous web pages touting it… Read More

• Drug Assays

  A Magic Methyl, Spotted in the Wild

  7 November, 2018

  You hear medicinal chemists talking about the “magic methyl”, the big effect that a single CH3 group can have on potency or selectivity. Here’s a new J. Med. Chem. paper that shows one in action.That structure looks like a kinase inhibitor if anything ever did, and so it is. But small changes to it can… Read More