A Structure From the Molecular Sponge
There's an interesting report from the Buchwald group using the Fujita "molecular sponge" crystallography technique. The last report on this was a correction, amid reports that the method was not as widely applicable as had been hoped, so I'm very happy to see it being used here. They're revising the structure of a new reagent (from the Lu and Shen groups in Shanghai) for introducing the SCF3 group. It was proposed to be a hypervalent iodine (similar to other reagents in this class), but Buchwald's group found some NMR data and reactivity trends that suggested the structure might be in the open form, rather than the five-...
Source: In the Pipeline - March 7, 2014 Category: Chemists Tags: Chemical News Source Type: blogs

Biggest US Cities for Biopharma Funding, Versus Whole Continents.
FierceBiotech has their roundup of the top areas of the US for venture capital funding in biopharma in 2013, and naturally, San Francisco and the Boston area are fighting it out for the top spot. But Oakland the the east Bay region are in a separate category, and if those are wrapped into the rest of SF, the whole Bay area wins out by a pretty good margin. But, as was pointed out by Nick Taylor on Twitter, San Francisco (not even counting Oakland, etc.) and Boston together raised more biopharma VC funding than all of Europe put together.(See slide 10 here). SF raised $1.15 billion, and Boston $0.93, while all of Europe wa...
Source: In the Pipeline - March 6, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs

We Are Pleased To Publish Your Senseless Ravings
There's been some (justified) hand-wringing in scientific publishing circles over the revelation that at least 120 abstracts and papers out there in the literature are complete nonsense generated by SciGen. (A few previous SciGen adventures can be found here and here) Some news reports have made it seem like these were regular full papers, but they're actually published conference proceedings which (frankly) are sort of the ugly stepchild of the science journal world to begin with. They're supposed to be reviewed, and they certainly should have been reviewed enough for someone to catch on to the fact that they were devoid ...
Source: In the Pipeline - March 6, 2014 Category: Chemists Tags: The Scientific Literature Source Type: blogs

Traveling Interruption
My visit to Illinois went well, and I had a very good time talking to the students and faculty here in Champaign/Urbana. But American Airlines has decided not to fly anyone to Chicago today, so I've had to round up alternative transportation and reschedule flights, which isn't going to leave much time for blogging, from the looks of it. So normal service, or what passes for it around here, will resume on Thursday! (Source: In the Pipeline)
Source: In the Pipeline - March 5, 2014 Category: Chemists Tags: Blog Housekeeping Source Type: blogs

More Good PD-1 News in Cancer
PD-1 therapies are a big, big deal in oncology these days, and with results like this, no wonder. It's a negative regulator of T-cell function, and blocking it appears to recruit a much stronger immune response to tumor cells. Bristol-Myers Squibb, Merck, and others have antibodies in the clinic, and results are piling up to suggest that these are going to be big. The BMS entry, BMS-936558 (nivolumab), had already shown some promising Phase II results in non small-cell lung cancer, renal carcinoma, and colorectal cancer. Many patients don't respond, but the ones that do seem to show real benefit. (And it's worth noting th...
Source: In the Pipeline - March 4, 2014 Category: Chemists Tags: Cancer Source Type: blogs

Novartis's Stealthy Headcount Reductions
Novartis has always been very, very quiet about their re-orgs and layoffs, to the point that when I and others write about them, we get hits from people at Novartis trying to find out what's going on. John Carroll at FierceBiotech has experience this as well, and he now has this story, from a reporter at the Swiss Tages-Anzeiger newspaper, that says that the company has actually eliminated between 3,000 and 4,000 jobs since last fall. That comes to about a thousand in Europe (500 of them in Basel), 760 in the US (mostly in the sales force), and 400 during the closure of Horsham in the UK. My impression is that many of the...
Source: In the Pipeline - March 4, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs

Sydney Brenner on the State of Science
Via Retraction Watch, here's an outspoken interview with Sydney Brenner, who's never been the sort of person to keep his opinions bottled up inside him. Here, for example, are his views on graduate school in the US: Today the Americans have developed a new culture in science based on the slavery of graduate students. Now graduate students of American institutions are afraid. He just performs. He’s got to perform. The post-doc is an indentured labourer. We now have labs that don’t work in the same way as the early labs where people were independent, where they could have their own ideas and could pursue them. The most...
Source: In the Pipeline - March 3, 2014 Category: Chemists Tags: General Scientific News Source Type: blogs

A Bit More Realism in Consulting
That McKinsey piece I mentioned the other day, the one saying that big drug mergers have pretty much worked out just fine, has been pretty thoroughly torn apart in the comments section. A reader has sent along another report from one of their competitors in the high-priced consulting game, this overview from Deloitte. Most readers won't find much in there that's new. But at least you won't find so many things in there that make you wonder what's in their water supply. And there are some non-rosy parts, for sure: While, the U.S. Food and Drug Administration (FDA) approved 39 new molecular entities in 2012, up from 31 in ...
Source: In the Pipeline - March 3, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs

Out to Illinois
I'll be visiting Illinois tomorrow to give a talk as part of the university's Chemistry-Biology Interface program. The first week of March is probably not the time to see the Champaign-Urbana landscape at its best, but then, I'm not leaving a lot of scenic grandeur behind in the Boston area this time of year, either. By March, winter's the guy who hasn't realized that everyone else at the party left a while ago. Fortunately, the snow that was forecast to mess with my flights today seems to have vanished, for once. . . (Source: In the Pipeline)
Source: In the Pipeline - March 3, 2014 Category: Chemists Tags: Blog Housekeeping Source Type: blogs

A Call To Rein In Phase III Trials
Here's a very nice perspective on what gets funded in drug research and why. Robert Kocher and Bryan Roberts bring their venture-capital viewpoint (Venrock) to the readers of the NEJM: It is not mysterious why projects get funded. As venture-capital investors, we evaluate projects along four primary dimensions: development costs, selling costs, differentiation of the drug relative to current treatments, and incidence and prevalence of the targeted disease (see table). For a project to be attractive, it needs to be favorably reviewed on at least two of these dimensions. Many drugs designed for orphan diseases and cancers ...
Source: In the Pipeline - February 28, 2014 Category: Chemists Tags: Clinical Trials Source Type: blogs

Computational Nirvana
Wavefunction has a post about this paper from J. Med. Chem. on a series of possible antitrypanosomals from the Broad Institute's compound collection. It's a good illustration of the power of internal hydrogen bonds - in this case, one series of isomers can make the bond, but that ties up their polar groups, making them less soluble but more cell-permeable. The isomer that doesn't form the internal H-bond is more polar and more soluble, but less able to get into cells. Edit - fixed this part. So if your compound has too many polar functionalities, an internal hydrogen bond can be just the thing to bring on better activity,...
Source: In the Pipeline - February 28, 2014 Category: Chemists Tags: In Silico Source Type: blogs

A Close Look at Receptor Signaling
Ah, the good old central nervous system, and its good old receptors. Especially the good old ion channels - there's an area with enough tricky details built into it to keep us all busy for another few decades. Here's a good illustration, in a new paper from Nature Chemical Biology. The authors, from Berkeley, are looking at the ionotropic glutamate receptors, an important (and brainbendingly complex) group. These are the NMDA, AMPA, and kainate receptors, if you name them by their prototype ligands, and they're assembled as tetramers from mix-and-match subunit proteins, providing a variety of species even before you start ...
Source: In the Pipeline - February 27, 2014 Category: Chemists Tags: Biological News Source Type: blogs

The Instructive Case of Galena Biopharma
If you're in the mood for another reason why you should always be cautious about your biopharma investments, look no further than Galena Biopharma (GALE to its many clueless fans). I've been following this story over the last couple of weeks, and what a mess it is. Galena is a small company in Oregon with a few assets, including a cancer vaccine candidate. Its stock hovers in the low single digits, as is appropriate. But in December and January, it began to trade up, and up. From $2/share to $4. Then to $6, and then higher. And this on no particular news or change in the company's prospects, which for a stock like this is ...
Source: In the Pipeline - February 26, 2014 Category: Chemists Tags: Business and Markets Source Type: blogs

Changes in Papers
Here's a look at some of the changes in JACS papers over the decades. Several trends are clear - there are more authors now, and single-author papers have almost vanished. Reference lists are much longer (which surely reflects both the sie of the literature and the relative ease of bibliography compared to the bound-volume/index card days). Have a look at the charts - François-Xavier Coudert, the blog's author, says that he'll be putting up some more later on, and I look forward to seeing what comes up. (Source: In the Pipeline)
Source: In the Pipeline - February 26, 2014 Category: Chemists Tags: The Scientific Literature Source Type: blogs

InterMune Comes Through
Back in 2010, I wrote about InterMune's drug for idiopathic pulmonary fibrosis, pirfenidone. The company's stock shot up on hopes that the compound would make it through the FDA, and then went straight back down when those proved ill-founded. The agency asked them for more data, and I wondered at the time if they'd be able to raise enough cash to generate it. Well, they did, and the effort appears to have been worth it: the company says it met all its endpoints in Phase III, and is headed back to the FDA with what appears to be a solid story. Note that this press release, as opposed to the Pfizer one that I was mentioning...
Source: In the Pipeline - February 25, 2014 Category: Chemists Tags: Clinical Trials Source Type: blogs