Sanofi and AZ share 210,000 compounds -can we go further?

In the Wall Street Journal today (section B), nestled under an article on Star Wars aim to be a Box -office behemoth, was a small article by Denise Roland on drug giants. This described  the news that AstraZeneca and Sanofi announced  they will each share 210,000 of their compounds from their 2-3 million libraries. This is unprecedented because of the scale of the sharing. To me it sends a message of desperation. each company has run out of avenues to pursue so lets borrow our competitor compounds.  That would be like in formula 1 if Ferrari swapped cars with Mercedes but kept the same drivers. They can no longer innovate themselves. They may as well all become virtual pharmaceutical companies, leveraging compounds that are commercially available globally or from academic collaborators and do not do any work in house. Frankly that may be more profitable. In recent days we saw Boston Pharmaceuticals headed by ex Sanofi CEO  Christopher Viehbacher emerge as a virtual pharma shop.

While the AZ spokesman suggested the compound collection is a means to an end. The reality is that many of those compounds in the 2 million collection were probably purchased or made for them by chemists at other companies. Some of these compounds see the light of day in patents and publications, so  are the companies really sharing secrets? The AZ spokesman suggests their differentiating factor is the ‘biologists and scientists’ working for them. (I always believed that biologists are scientists – but seems that we are now a different species). Actually, as reported previously, the most important aspect of the screening of such compounds may be how they are dispensed and as we know AZ definitely use acoustic dispensing. I am not sure what Sanofi use, but small things like this could have a big impact on screening success. The article does not touch on the quality of such screenng data and also misses that many companies use virtual screening of massive libraries before focusing on compounds they can buy from vendors.

In the past we have proposed drug companies shared not just their compounds but their ADME/Tox data or models. I think that would have far more impact on productivity than sharing 10% of their cast off compounds. Like the GSK sharing of malaria and TB data in the past, this is just a small token effort, when what is really needed is something more transformational. For example all drug companies could collaborate to share all their libraries, or just their shelved compounds. They could all share their ADME/Tox data or models. The technologies exist for secure and selective sharing of data. Such examples of collaborations already exist and are funded by the NIH, EC, BMGF as well as others. I believe these will be the template which pharmas will ultimately use for all their research (eventually). In the meantime, I think that smaller, nimbler virtual pharma type companies may have the upper hand while large pharma try to stay relevant by slowly adapting and collaborating with each other.


Male : female ratios on scientific websites, conferences and journal editorial boards

My young children (girl + boy) are interested in science, thankfully, heavily influenced by us as parent scientists and the museums and the scientists that they get to meet. But it has caused me to consider what the situation will be like in future for my daughter. What if? What if she continues with science and I think there is a strong bias towards chemistry and biology. What next? What if she is able to go into academia, what are the prospects? We are surrounded by science that is online (products, journals and news) and I started to notice what has probably been flagged many times before. Just looking at websites and images, the way we portray scientists is just plane biased – its basically white and male. What impact does that have on encouraging girls and minorities to get into STEM? Does it have some influence. I spend all day at my computer am I influenced too?

In the last 24 hrs I happened to look at one website F1000 which has very useful open access journal  and analysis of science literature products and was struck by the predominantly old and male photographs of scientists. The ratio was 4:1 in favor of males with large photos and 2:1 for smaller headshots. I reached out to my contact there to point this out and I hope they take my observation in the way it was intended.

Then I received an email for a EuroQSAR conference in Europe next year. I glanced at the confirmed speaker list and it was 5 out of 18 were female as far as I could tell. This reminded me of a QSAR Gordon conference in 1999 which was probably 90% male and 4 out of 21 speakers were female.

I wondered whether this ratio is the same at top journals. So the low hanging fruit is Science, I looked at the senior editorial board of 5 scientists 4:1 in favor of males. The massive board of reviewing editors also looks heavily weighted towards males as far as I could tell. How much deeper do you want to dig ?

I submit these are just a few examples, and I am still processing the implications. I am a male scientist over the age of 40.  I have contributed to conferences (many predominantly male speakers) and I am on journal editorial boards e.g. Pharmaceutical Research (4 out of 13 are female) and Drug Discovery Today (6 out of 50 are female). I think we can have some say in transforming the ratio and increasing the diversity of scientists. We have addressed the growth in submissions of manuscripts from Asia by adding editors from this region, why not re-balance our website images, editorial boards and meetings to ensure that we have more diversity overall.

This is probably just the tip of the iceberg, but if our daughters are to have more opportunity in science in the future I think we need to start addressing it now. I just cannot believe that the way scientists are portrayed on websites, how they are represented on editorial boards and in conferences is accurate, predominantly male. This must have a negative influence on young female students. It may be uncomfortable to have to deal with this. But we have to start.



Giving Tuesday- Giving changed me too

I wanted to help Jonah’s Just Begun so I contributed this to Giving Tuesday..please give it a vote..

November marks the anniversary four years ago that led to my commitment to try to help families find the cure for rare diseases that affect their children. One meeting at a conference led to a cascade of events that has since had a significant impact on my scientific research, collaborations, and colors virtually everything I do.

I am inspired to give my time and money by people that do or want to do the unexpected. For 99.99% of the population it would be something that is virtually impossible to do. Jill Wood as the co-founder of Jonah’s Just Begun described to me back in November 2011, doing just this, pulling together the knowledge, scientists and funds so that she could catalyze research into her son Jonah’s rare disease called Sanfilippo syndrome. In the years since, Jill went further, she started to have the same impact on other closely related diseases, and together this led us to found a company as an additional way to go after National Institutes of Health funding for the research performed at academic institutions.

How many parents could do all this one might ask? Jill introduced me to another parent with a rare disease foundation called Hannah’s Hope Fund (who has funded a gene therapy and brought it to clinical trial), and in turn she introduced me to yet another rare disease parent who started the Hereditary Neuropathy Foundation. All of them are parents, not scientists I might add, doing the seemingly impossible, scouring the world to find research that could catalyze a treatment to be developed. How could this not inspire you to help and donate your time and money to all their causes? At the same time it made me recalibrate what was possible. A little time and money devoted to their causes could go a long way.

Every November I remember that moment that kicked it off, Jill sitting across from me describing a heart wrenching story every parent would dread, being told her child had a fatal disease. Now every scientist I meet I tell them the same story and it leads to new connections, scientists I should meet, compounds to test and more. We are not alone in wanting our research to be funded, to succeed, to be published, and to be shared for the benefit of humankind. While at times it may seem what we do is far removed from the clinic, thousands of parents of children with rare diseases depend on us and our skills. Many scientists will not realize the importance of what we can offer until they meet people like Jill, for whom nothing is impossible. We can directly help rare disease parents and families in varied ways by giving our time, our advice, our financial support and letting them know that they are not alone in their quest for a cure. I have done all of these and it has changed me and what I do. Nothing is impossible or unattainable, we work hard, and we find people that can help us achieve the goal.

Supporting and giving to rare disease foundations like Jonah’s Just Begun, Hannah’s Hope Fund and the Hereditary Neuropathy Foundation can have positive unintended consequences. It can alter your perspective on what is truly important in life. It may even change your career, lead to a new business idea, create jobs, develop products, and hopefully cure the disease. If one person leading each foundation could make all this happen over and over again then our giving either in time, expertise or money can be a powerful multiplier that creates giving stories that demand sharing repeatedly and provides hope for the families who are living with these diseases.


Pros and Cons of Social Networking for Scientists: Its not just about Me

I have Antony Williams to thank because for a long time I have been wanting to summarize my thoughts on how I use social networking to spread the word about the science that I am involved in. Seeing Tony’s slides pushed me to do this!

This follows visiting many groups of students (most recently at Rutgers-Camden) over the years and coming away with the feeling this is not something that is taught, its something you acquire or pick up. So lets change that, can we show students how to benefit from the social networking tools for science that are out there, what to watch out for etc. The intertia to put something together combined with time constraints provided a small window of opportunity.. It was this week or never.

It is probably far easier for me to put a presentation together than write about this in gory detail. So here goes. If you want me to come and talk to your students or group on this I would be happy to oblige.


Learning from pioneers in science from the 20th Century

Having just completed review of a manuscript that profiled a prominent scientist in my field from the 20th century, it got me thinking openly.

Firstly, I rarely read profiles of long deceased scientists in my field, frankly who but perhaps the odd emeritus professor (with all due respect) would have time on their hands to write them, let alone read them, between writing grants or trying to hold on to a job in industry. Sadly it is more likely we would now write articles in honor of departed colleagues. Does that say something that we do not have the time to celebrate the achievements of a few titans that published hundreds of papers before computers and software to track the literature as we know them today. One would hope that Wikipedia could do a half decent job of this, but its very weak when it comes to scientists, even the living key scientists, as we have discussed in the past.

But perhaps we do need to capture such historic information because we can learn how fields of science evolve, how today’s discoveries came from their foundational work. It is not that I am getting nostalgic for the good old days, but reviewing the paper got me thinking about scientific lineage and how I have a responsibility to pass what I have picked up onto the next generation. If we do not write such oral histories down, how will the people that taught me be remembered otherwise. However much we may or may not have got on with our PhD (or other academic) mentors, they played a part in getting us to where we are, and we in turn contributed to their published legacy.

Do I want to be remembered as someone that worked on many enzymes in liver slices during my PhD? No. But this work and critical time in my education is reflected in what I do now and why my interests are quite diverse. As students in a scientific area we should perhaps have some historical context for what we are doing, beyond it being topical and funded by a grant etc. It may pay to go back and see how much of the pioneering work in a field was actually funded by grants from governments or foundations. That may be an interesting analysis I would certainly read. Namely can we get the next generation of pioneers to innovate by funding them or starving them of funds? Sure, people will leave the field, but those truly committed to an idea, will find a way to do the experiment and fund it. Perhaps those are the ones we will read about later in the 21st century as shaping science.




Collaboration to find compounds active against Ebola

Our latest contribution to the Ebola literature came out today. A collaboration with Peter Madrid (SRI International), Robert Davey and Manu Anantpadma (Texas Biomedical Research Institute), Alex Clark (Molecular Materials Informatics) and Joel Freundlich (Rutgers).

Last year I posted a few times on Ebola here, here  here and here. This interest all stemmed from some Tweets shared with Chris Southan and Megan Coffee. This in turn lead to a little work on the antimalarials and SERMs that came out of the earliest HTS screens to try to identify a target.  I told most of the story at the ACS a few months ago.

Well to summarize, I initially reached out to Peter Madrid to access his HTS data from screening a library against Ebola in vitro. He had some unpublished data to add as well. This enabled me to build some Bayesian models and do some compound library searching. Joel kindly interpreted the features in the active and inactive molecules. Initially this work was going to be a part of the pharmacophore paper, but it was held out so that Peter could get some data out. This was ideal because I started to put a draft together for the ISCB competition, by this point I had also reached out to Robert Davey. I had picked 3 compounds that scored well (got Joel’s blessing) and were not in the training set. Peter purchased the compounds and Manu and Robert kindly tested them. During this time I had also looked at model building with other software/ algorithms and with Alex’s help made the models available for use with mobile apps. Initial in vitro results looked good and were available before the ACS presentation and since then addition in vitro work provided more confidence. The bottom line was we were able to find 3 compounds with activity in the hundreds of nM range. Interestingly 2 of these compounds were also identified as part of the earlier pharmacophore work for VP35. What is interesting is the 3 compounds have not been identified previously. Pyronaridine is used as part of an antimalarial combination drug. Quinacrine is an old antimalarial and anthelmintic while Tilorone is is an investigational antiviral with broad biological activity.

The next step is trying to get the compounds tested in the in vivo model of Ebola infection. It is hard to believe its taken a year to get to this point, and still people are dying from Ebola in Africa. I hope we can get further and provide some hope.


Old drug, no news: deceased Chemist on front page of Wall Street Journal

Albert Hofmann passed away in 2008 but today he made it to the front page of the Wall Street Journal (WSJ), surrounded by articles on Syria, Wal-Mart, the Canadian election and megadeals. I am still trying to figure out why the location of the old papers and notebooks of this chemist was newsworthy. Could it be because Sandoz / Novartis did not want them because of the association with LSD (this will have zero impact on their stock price)? Could it be because the chemist wanted people to flock to his archive and no one was even remotely interested?  Could it be that his archive traveled to the US and then back to Europe before finding a home? Whatever the reason, should we be grateful that a scientist (a chemist) was on the cover of a major newspaper? It certainly draws attention to chemists following the recent Medicine Nobel prize going to scientists working on natural products. But surely there must be more newsworthy articles they could write that would engage readers today with how chemistry can have a positive impact on our lives. LSD was discovered in 1943, a considerable number of discoveries have been made since then both for healthcare and reflected in consumer products, which have had massive financial impact which readers of the WSJ would care about. I am not so sure that LSD has had a huge financial impact except for those making and selling it illegally. Even the idea of LSD making a resurgence with clinical trials is not really borne out based on the few clinical trials in Perhaps the story that would be of interest here is how Sandoz cannot really make any money from LSD (as the patents expired in the 1960s) and therefore they really have no interest in an old employee and his notebooks (although technically they own them). In the future this kind of thing will not make the front page because the notebooks will be electronic in most cases and likely kept confidential. That’s progress.


ninth chapel hill pharmaceutical sciences conference

Today I am at a local conference at UNC and you can find me live tweeting under #PharmSci15 . Conference link is here.


Posters and talks at SERMACS

I will be attending the upcoming SERMACS meeting in Memphis November 4-7, 2015 and here are the following talks and poster accepted this week. Hope to see you there.

ABSTRACT ID: 2352895
ABSTRACT TITLE: Combining metabolite-based pharmacophores with Bayesian machine learning models for Mycobacterium tuberculosis drug discovery (Final paper number: 13)

SESSION: General Computational Chemistry
SESSION TIME: 8:00 AM – 12:20 PM

DAY & TIME OF PRESENTATION: Wednesday, November, 04, 2015 from 8:00 AM – 8:20 AM
ROOM & LOCATION: L-6 – Cook Convention Center
ABSTRACT ID: 2352920
ABSTRACT TITLE: CDD Vision: A new reactive web platform for multidimensional drug discovery data mining and visualization (Final paper number: 340)

SESSION: General Computational Chemistry
SESSION TIME: 8:00 AM – 10:00 AM

DAY & TIME OF PRESENTATION: Thursday, November, 05, 2015, 8:00 AM – 10:00 AM
ROOM & LOCATION: West Mezzanine – Cook Convention Center

ABSTRACT ID: 2353359
ABSTRACT TITLE: CDD Vault, CDD Vision, and CDD Models for drug discovery collaborations (Final paper number: 886)

SESSION: Drug Discovery Technologies
SESSION TIME: 8:00 AM – 12:00 PM

DAY & TIME OF PRESENTATION: Saturday, November, 07, 2015 from 8:00 AM – 8:40 AM
ROOM & LOCATION: River Bluff Room – Cook Convention Center


Nobel prize in medicine – going back to natural products for drugs

Every year there are potentially 1000’s of scientists that could have won the Nobel prize and did not. This year the prize recognizes 3 scientists for their work on parasitic diseases.  William Campbell  and Satoshi Omura won for their work on discovering Avermectin which lead to treatments for River Blindness and Lymphatic Filariasis. Youyou Tu also won for her work on Artemisinin as a treatment for malaria. Although I am sure most of the press reports will miss this obvious link. Both drugs are natural products. Avermectin comes from Streptomyces avermitilis and Artemisinin comes from the sweet wormwood tree. So this points to where drug discovery was focused 30-40 years ago before the use of combinatorial libraries and large high throughput screens was routine. Unlike in recent years, the Nobel committee is not recognizing recent basic science work but drug discovery science from decades ago. One can only wonder if this is a stab at the pharmaceutical industry. Also it is hard to remember the last time this prize was given for drug discovery, let alone anything for parasitic diseases. Maybe the work of Paul Muller and discovery of DDT comes to mind and he won his award in 1948. We all know how that played out and decades later was banned. Before that there was the 1945 award to Alexander Fleming, Ernest Chain and Howard Florey for discovery of Penicillin. Prior to this there was Gerhard Domagk who got his prize in 1939 for discovery of prontosil, an earlier antibiotic. So you can count on your fingers how many scientists have won the Nobel prize in medicine for discovering drugs. Perhaps in 30-40 years they will be giving out the next prize for drug discovery and if so what will it be for, immunotherapy, antibody drug conjugates, gene therapy..Its hard to predict, all I know is by then I will be the average age of some of these recipients now! I just hope we find cures for many of the neglected diseases that continue to kill millions of people before then.


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