GPCRs As Drug Targets: Nowhere Near Played Out
Here's a paper that asks whether GPCRs are still a source of new targets. As you might guess, the answer is "Yes, indeed". (Here's a background post on this area from a few years ago, and here's my most recent look at the area).
It's been a famously productive field, but the distribution is pretty skewed:
From a total of 1479 underlying targets for the action of 1663 drugs, 109 (7%) were GPCRs or GPCR related (e.g., receptor-activity modifying proteins or RAMPs). This immediately reveals an issue: 26% of drugs target GPCRs, but they account for only 7% of the underlying targets. The results are heavily skewed by certain ...
Source: In the Pipeline - August 20, 2013 Category: Chemists Tags: Drug Assays Source Type: blogs
Too Many Biotech IPOs?
It's worth noting, on the business end of things, that we seem to be in a boom period for biotech/small pharma IPOs. I don't think anyone saw that coming, but these things take on momentum of their own. Hardly anyone went public for a few years once the financial crisis hit in 2007/2008. Then last year there were eleven new public companies, the most in quite a while. This year, though, there have been 29 (according to this piece in FierceBiotech), with eight of them since just the end of June.
That's pretty lively. And while some of this can be explained as a holdover from companies that would have gone public earlier, u...
Source: In the Pipeline - August 20, 2013 Category: Chemists Tags: Business and Markets Source Type: blogs
An Inspirational Quote from Bernard Munos
In the comments thread to this post, Munos has this to say:
Innovation cannot thrive upon law and order. Sooner or later, HR folks will need to come to grips with this. Innovators (the real ones) are rebels at heart. They are not interested in growing and nurturing existing markets beccause they want to obliterate and replace them with something better. They don't want competitive advantage from greater efficiency, because they want to change the game. They don't want to optimize, they want to disrupt and dominate the new markets they are creating. The most damaging legacy of the process-minded CEOs who brought us the inn...
Source: In the Pipeline - August 19, 2013 Category: Chemists Tags: Who Discovers and Why Source Type: blogs
Is The FDA the Problem?
A reader sends along this account of some speakers at last year's investment symposium from Agora Financial. One of the speakers was Juan Enriquez, and I thought that readers here might be interested in his perspective.
First, the facts. According to Enriquez:
Today, it costs 100,000 times less than it once did to create a three-dimensional map of a disease-causing protein
There are about 300 times more of these disease proteins in databases now than in times past
The number of drug-like chemicals per researcher has increased 800 times
The cost to test a drug versus a protein has decreased ten-fold
The technology to ...
Source: In the Pipeline - August 19, 2013 Category: Chemists Tags: Drug Development Source Type: blogs
High Throughput Screening Services
Here's a question that comes up once in a while in my e-mail. I've always worked for companies that are large enough to do all of their own high-throughput screening (with some exceptions for when we've tried out some technology that we don't have in-house, or not yet). But there are many smaller companies that contract out for some or all of their screening, and sometimes for some assay development as well beforehand.
So there are, naturally, plenty of third parties who will run screens for you, against their own compound collections or against something you bring them. A reader was just asking me if I had any favorites...
Source: In the Pipeline - August 19, 2013 Category: Chemists Tags: Drug Assays Source Type: blogs
An HIV Structure Breakthrough? Or "Complete Rubbish"?
Structural biology needs no introduction for people doing drug discovery. This wasn't always so. Drugs were discovered back in the days when people used to argue about whether those "receptor" thingies were real objects (as opposed to useful conceptual shorthand), and before anyone had any idea of what an enzyme's active site might look like. And even today, there are targets, and whole classes of targets, for which we can't get enough structural information to help us out much.
But when you can get it, structure can be a wonderful thing. X-ray crystallography of proteins, and protein-ligand complexes has revealed so muc...
Source: In the Pipeline - August 16, 2013 Category: Chemists Tags: Analytical Chemistry Source Type: blogs
Mannkind's Latest Data
I haven't written much about Mannkind recently. This has been a long, long, expensive saga to develop an inhaled-insulin delivery system (Afrezza), which is an idea that all by itself has seems to have swallowed several billion dollars and never given anything back yet. (That link above will send you to some of the story, and this one will tell you something about the disastrous failure of the only inhaled insulin to reach the market so far).
In 2011, Mannkind looked as if they were circling the drain. But (as has been the case many times before), more money was heaved into what might still turn out to be an incinerator, ...
Source: In the Pipeline - August 15, 2013 Category: Chemists Tags: Diabetes and Obesity Source Type: blogs
Aileron Reports Some Stapled Peptide Results
Here's a publication from Aileron Therapeutics on their stapled-peptide efforts against MDM2/p53 for cancer. (I wrote about that target here, so you can check out the links in that post for background). This compound (ATSP-7041) goes after both MDM2 and MDMX, activating the suppressed p53 pathway, and it seems to do a good job of it. The company's been talking about these results at conferences, but this is the official publication of all that data.
Stapled peptides as a class of potential drugs have been the subject of controversy, but this one is heading towards the clinic, by all accounts. There are several other compo...
Source: In the Pipeline - August 15, 2013 Category: Chemists Tags: Cancer Source Type: blogs
Big Pharma And Its Research Publications
A longtime reader sent along this article from the journal Technological Forecasting and Social Change, which I'll freely admit never having spent much time with before. It's from a team of European researchers, and it's titled "Big Pharma, little science? A bibliometric perspective on Big Pharma's R&D decline".
What they've done is examine the publication record for fifteen of the largest drug companies from 1995 to 2009. They start off by going into the reasons why this approach has to be done carefully, since publications from industrial labs are produced (and not produced) for a variety of different reasons. But in th...
Source: In the Pipeline - August 15, 2013 Category: Chemists Tags: The Scientific Literature Source Type: blogs
Now It's Novartis's Turn in China
So reports FiercePharma, quoting a story in the 21st Century Business Herald and the Shanghai Daily. A former Novartis sales rep says that she was "ordered" to bribe doctors to meet sales quotas. As Tracy Staton at Fierce puts it:
With Chinese authorities actively looking for any suggestion of corruption or bribery, we're likely to see more whistleblowers come forward and officials investigations follow. Though no one wants to admit it, payments to doctors and hospitals have been commonplace in China for years. The BBC reported this week that bribes are "routinely paid" by big drugmakers in China, citing 5 pharma reps wor...
Source: In the Pipeline - August 14, 2013 Category: Chemists Tags: Business and Markets Source Type: blogs
A Regeneron Profile
In the spirit of this article about Regeneron, here's a profile in Forbes of the company's George Yancopoulos and Leonard Schleifer. There are several interesting things in there, such as these lessons from Roy Vagelos (when he became Regeneron's chairman after retiring from Merck):
Lesson one: Stop betting on drugs when you won’t have any clues they work until you finish clinical trials. (That ruled out expanding into neuroscience–and is one of the main reasons other companies are abandoning ailments like Alzheimer’s.) Lesson two: Stop focusing only on the early stages of drug discovery and ignoring the later stage...
Source: In the Pipeline - August 14, 2013 Category: Chemists Tags: Drug Development Source Type: blogs
Another T-Cell Advance Against Cancer
The technique of using engineered T cells against cancerous cells may be about to explode ever more than it has already. One of the hardest parts of getting this process scaled up has been the need to extract each patient's own T cells and reprogram them. But in a new report in Nature Biotechnology, a team at Sloan-Kettering shows that they can raise cells of this type from stem cells, which were themselves derived from T lymphocytes from another healthy donor. As The Scientist puts it:
Sadelain’s team isolated T cells from the peripheral blood of a healthy female donor and reprogrammed them into stem cells. The researc...
Source: In the Pipeline - August 14, 2013 Category: Chemists Tags: Cancer Source Type: blogs
Nanorods? Or Photoshop?
If you haven't seen this, which goes into some very odd images from a paper in the ACS journal Nano Letters, then have a look. One's first impression is that this is a ridiculously crude Photoshop job, but an investigation appears to be underway to see if that's the case. . . (Source: In the Pipeline)
Source: In the Pipeline - August 14, 2013 Category: Chemists Tags: The Scientific Literature Source Type: blogs
Druggability: A Philosophical Investigation
I had a very interesting email the other day, and my reply to it started getting so long that I thought I'd just turn it into a blog post. Here's the question:
How long can we expect to keep finding new drugs?
By way of analogy, consider software development. In general, it's pretty hard to think of a computer-based task that you couldn't write a program to do, at least in principle. It may be expensive, or may be unreasonably slow, but physical possibility implies that a program exists to accomplish it.
Engineering is similar. If it's physically possible to do something, I can, in principle, build a machine to do it.
...
Source: In the Pipeline - August 13, 2013 Category: Chemists Tags: Drug Development Source Type: blogs
Sanofi in China
Now Sanofi is tangled up in trouble in China. The last few days have brought news of a wide-ranging investigation into payments to hospitals and medical workers, similar to what GlaxoSmithKline has been accused of.
And I don't have much reason to doubt either story, because (as this BBC story details) payments of this sort are rife. I would also note that, according to the AP, the Chinese government "is investigating production costs at 60 Chinese and foreign pharmaceutical manufacturers, according to state media, possible as a prelude to revising state-imposed price caps on key medications."
A system where everyone is ...
Source: In the Pipeline - August 13, 2013 Category: Chemists Tags: Business and Markets Source Type: blogs
