Jailhouse Secrets They Don't Want You to Know About!
As I had hoped last year, scam artist Kevin Trudeau is indeed heading off for a ten-year sentence. I have searched, without success, for a photo of him wearing an orange jumpsuit and being bundled into a windowless prison van, but we'll just have to use our imaginations for that. Not to worry - a good steam cleaning, and the vehicle will be surely be fit to transport honest burglers again.
Trudeau had been convicted of criminal contempt, for egregiously violating earlier court orders to stop ripping people off through his all-natural-cures informercial empire. Past entries here have detailed what the man is like, and if y...
Source: In the Pipeline - March 18, 2014 Category: Chemists Tags: Current Events Source Type: blogs
What If Total Syntheses Had Only 25 Steps to Work In?
In conclusion, this article tries to show how various strategies may be used to streamline and to shorten otherwise long synthetic routes to complex target molecules. The reader may get the impression that it pays very well to think intensively about cascade reactions, intramolecular cycloadditions, suitable starting materials and so on, instead of plunging into a brute-force and therefore mostly inefficient sequence. After all, there is an iron maxim: if a target cannot be reached within, say, 25 steps, it is better to drop it. For what you will get is a heroic synthesis, at best, but never an efficient one.
A 25-step l...
Source: In the Pipeline - March 17, 2014 Category: Chemists Tags: Chemical News Source Type: blogs
Predicting What Group to Put On Next
Here's a new paper in J. Med. Chem. on software that tries to implement matched-molecular-pair type analysis. The goal is a recommendation - what R group should I put on next?
Now, any such approach is going to have to deal with this paper from Abbott in 2008. In that one, an analysis of 84,000 compounds across 30 targets strongly suggested that most R-group replacements had, on average, very little effect on potency. That's not to say that they don't or can't affect binding, far from it - just that over a large series, those effects are pretty much a normal distribution centered on zero. There are also analyses that clai...
Source: In the Pipeline - March 17, 2014 Category: Chemists Tags: In Silico Source Type: blogs
Going After Poor Published Research
This should be interesting - John Ioannidis, scourge of poorly reproducible published results, is founding an institute at Stanford. The Economist has more:
They will create a “journal watch” to monitor scientific publishers’ work and to shame laggards into better behaviour. And they will spread the message to policymakers, governments and other interested parties, in an effort to stop them making decisions on the basis of flaky studies. All this in the name of the centre’s nerdishly valiant mission statement: “Identifying and minimising persistent threats to medical-research quality.”
It will be most interes...
Source: In the Pipeline - March 14, 2014 Category: Chemists Tags: The Scientific Literature Source Type: blogs
The Genetics of Bipolar Disorder: What A Tangle
Here's a brave attempt to look for genetic markers of bipolar disorder. The authors studied 388 Old Order Amish sufferers, doing thorough SNP analysis on the lot and total sequencing on fifty of them. There were many parent-child relationships in the set, which gave a chance for further discrimination. And the result:
. . .despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implicatio...
Source: In the Pipeline - March 14, 2014 Category: Chemists Tags: The Central Nervous System Source Type: blogs
A Sirtuin Activator Extends Lifespan in Normal Mice
If you haven't seen it, the Sinclair group and numerous co-workers at the NIH and elsewhere now report that the SIRT1 activator SRT1720 extends the lifespan of mice on a diet of normal chow, and they see a number of good metabolic indicators - increase fat oxidation, decrease fat mass, increased insulin sensitivity, and so on.
There are several things to note about this effect, though. The mice were started on the compound at six months of age, and the compound was supplemented in chow to a dose of 100 mpk, which was maintained from there on out. (I don't have any allometric tables to hand, but it's safe to say that this ...
Source: In the Pipeline - March 14, 2014 Category: Chemists Tags: Aging and Lifespan Source Type: blogs
The Reasons for Failure at the FDA
Here's a good retrospective in JAMA, from the FDA, about what's happened when the agency has rejected a new molecule entity (NME). The authors look over the data set from 2000-2012 to see what the most common reasons for trouble were, and what happened after that in each case.
Overall, 302 new molecules were submitted during those years. Half of them were rejected the first time through - a figure that does not jibe with most investors' ideas of the prospects for any given drug, for sure. But Tolstoy was right - approved drugs are all alike, but every rejected one is rejected in its own way. Looking over those, it appears...
Source: In the Pipeline - March 13, 2014 Category: Chemists Tags: Regulatory Affairs Source Type: blogs
A New NMR Probe Technology in the Making?
This paper is outside of my usual reading range, but when I saw the title, the first thing that struck me was "NMR probes". The authors describe a very sensitive way to convert weak radio/microwave signals to an optical readout, with very low noise. And looking over the paper, that's one of the applications they suggest as well, so that's about as far into physics as I'll get today. But the idea looks quite interesting, and if it means that you can get higher sensitivity without having to use cryoprobes and other expensive gear, then speed the day. (Source: In the Pipeline)
Source: In the Pipeline - March 12, 2014 Category: Chemists Tags: Analytical Chemistry Source Type: blogs
Stem Cell Shakedown Cruise
OK, now that recent stem cell report is really in trouble. One of the main authors, Teruhiko Wakayama, is saying that the papers should be withdrawn. Here's NHK:
Wakayama told NHK he is no longer sure the STAP cells were actually created. He was in charge of important experiments to check the pluripotency of the cells.
He said a change in a specific gene is key proof that the cells are created. He said team members were told before they released the papers that the gene had changed.
Last week, RIKEN disclosed detailed procedures for making STAP cells after outside experts failed to replicate the results outlined in the ...
Source: In the Pipeline - March 12, 2014 Category: Chemists Tags: Biological News Source Type: blogs
Compassionate Use: An Especially Tough Case
Update: Chimerix says this evening that they will make their drug available to the boy in question as part of a new 20-patient open-label trial, after discussions with the FDA. This might have been the best way out of this, if it gives the company a better regulatory path forward at the same time. My guess, though, is that the company's position was becoming impossible to maintain no matter what.
Many of you will have seen the stories of a dying 7-year-old whose parents are seeking compassionate use access to a drug being developed by Chimerix. It's hard reading for a parent, or for anyone.
But I can do no better than ec...
Source: In the Pipeline - March 11, 2014 Category: Chemists Tags: Drug Development Source Type: blogs
Always Insist on Error Bars
That's the take-home of this post by Adam Feuerstein about La Jolla Pharmaceuticals and their kidney drug candidate GCS-100. It's a galectin inhibitor, and it's had a rough time in development. But investors in the company were cheered up a great deal by a recent press release, stating that the drug had shown positive effects.
But look closer. The company's bar-chart presentation looks reasonably good, albeit with a binary dose-response (the low dose looks like it worked; the high dose didn't). But scroll down on that page to see the data expressed as means with error bars. Oh dear. . .
Update: it's been mentioned in the...
Source: In the Pipeline - March 11, 2014 Category: Chemists Tags: Clinical Trials Source Type: blogs
Startups vs. Big Pharma
Bruce Booth has opened up the number of authors who will be posting at LiveSciVC, and there's an interesting post up on startups now from Atlas Ventures' Mike Gilman. Edit: nope, my mistake. This is Bruce Booth's! Here are some of his conclusions:
here’s a list of a few of the perceived advantages of Pharma R&D today:
Almost unlimited access to all the latest technologies across drug discovery, ADME, toxicology, and clinical development, including all the latest capital equipment, compound libraries, antibody approaches, etc
International reach to support global clinical and regulatory processes to fully enable drug de...
Source: In the Pipeline - March 10, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs
A Blood Test for Alzheimer's?
Update: more doubts on the statistical power behind this, and the coverage it's getting in the press.
There's word of a possible early diagnostic blood test for Alzheimer's. A large team (mostly from Georgetown and Rochester) has published a paper in Nature Medicine on their search for lipid-based markers of incipient disease. They say that they have a ten-lipid panel that has a 90% success rate in predicting cognitive decline within three years.
I can certainly see how this would be possible - lipids could be markers of membrane trouble and myelin trouble, and we already know that the lipoprotein ApoE4 is linked with A...
Source: In the Pipeline - March 10, 2014 Category: Chemists Tags: Alzheimer ' s Disease Source Type: blogs
Repurposing for Cervical Cancer
One of the questions I was asked after my talk at Illinois was about repurposing drugs. I replied that there might be some opportunities there, but I didn't think that there were many big ones that had been missed, unless new biology/target ID turned up. Well, here's a news story that contradicts that view of mine, and I'm welcome to be wrong this time.
Researchers in Manchester have been working on the use of lopinavir (an existing drug for HIV) as a therapy for HPV, the cause of most cervical cancers. There's a vaccine for it now, but that doesn't do much for women who are already diagnosed with probable or confirmed d...
Source: In the Pipeline - March 10, 2014 Category: Chemists Tags: Cancer Source Type: blogs
Some New Reviews
Walensky and Bird have a Miniperspective out in J. Med. Chem. on stapled peptides, giving advice on how to increase one's chances of success in the area. Worth checking out, unless you're at Genentech or WEHI, of course. The authors might say that it's especially worth reading in those cases, come to think of it. I await the day when this dispute gets resolved, although a lot of people awaited the day that the nonclassical carbocation controversy got resolved, too, and look how long that took.
And in Science, Tehshik Yoon has a review on visible-light catalyzed photochemistry. I like these reactions a lot, and have run a ...
Source: In the Pipeline - March 7, 2014 Category: Chemists Tags: Chemical News Source Type: blogs
