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 "Toxicology"

• Cancer

  An Unexpected Halt in Multiple Myeloma for Venetoclax

  20 March, 2019

    Venetoclax (ABT-199) is an unusual drug. But now there’s some unusually bad (and unexpected) news about it. That’s the structure at right, and medicinal chemists will understand immediately why it’s a bit of an outlier. With a molecular weight of 868, that structure just keeps on going, with a somefeatures that you donR… Read More

• Business and Markets

  Zafgen: Will There Be a Third Act?

  14 March, 2019

  A few years ago on this blog, I wrote several times about a small company called Zafgen and their unusual epoxide-based chemical matter (beloranib) that was in development for the rare Prader-Willi syndrome. That’s a genetic disorder that includes, among many other problems, constant hunger (with the complications that you’d expect fro… Read More

• "Me Too" Drugs

  Proteasome Inhibitors, Refined

  27 February, 2019

  The proteasome is quite the structure. It is the shredding unit of the cell, where no-longer-needed proteins go to be ripped down to their components for recycling, and it’s become a more and more important part of drug discovery over the years. For one thing, all this fashionable targeted protein degradation work is about sending… Read More

• Business and Markets

  The Clinic Giveth And Most Definitely Taketh Away

  7 February, 2019

  There have been some pretty dramatic clinical trial results coming out recently, and unfortunately drama is a variable that can take either a positive or a negative sign in front of it. On the plus side, MacroGenix, a company that not many people had been paying attention to, announced results of a head-to-head trial of… 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

• 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

• Biological News

  Real Progress in Parkinson’s

  2 November, 2018

  There have been some potentially significant developments in Parkinson’s disease, which is a good thing to be able to report. As populations age around the world, PD has been on its way up, but therapies for it have not been, despite a good deal of work in the field. But it looks like some clues… Read More

• Clinical Trials

  Digging Into the Genetics of Drug Targets

  12 September, 2018

  Rare diseases – remember years ago, back when those were a case of market failure? When companies were reluctant to work on them because the market size was guaranteed to be small and you’d have to charge, like, a hundred thousand or more a year to make the whole idea financially viable? Which wasn’t going… Read More

• Cancer

  Why Not Target DNA? Well. . .

  28 June, 2018

  There are all sorts of small-molecule drugs that bind to protein targets. Active sites of enzymes are, of course, a big subset of those, but there are plenty of enzymes whose allosteric sites are known to host synthetic ligands as well. Membrane receptor and ion channel proteins get both of those mechanisms too, and then… Read More