31 December 2008
SGX relied heavily on crystallographic discovery of fragments, and their efforts towards inhibitors of JAK-2, a protein tyrosine kinase target for myloproliferative disorders, began by crystallizing the protein and performing fragment-soaking experiments. A bromoaminoindazole fragment with a mid-micromolar IC50 and high ligand efficiency was found to bind to the hinge region of the kinase. Examination of the crystal structure revealed a hydrophobic groove nearby, and replacement of the bromine by a phenyl group boosted the affinity by a factor of 25. Further elaboration of the phenyl group improved the IC50 to 78 nM, more than 500-fold better than the initial fragment. The molecule also exhibited respectable (38-fold) selectivity over JAK-3. Although ligand efficiency fell throughout the optimization process, it remained high; the final molecule remains relatively small and does not appear to violate Lipinski’s Rule of Five. There is no mention of cell activity or other pharmaceutical properties, but the authors do promise future publications.
In closing out this year, we would like to thank everyone for reading, and especially for commenting. Please pass along any fragment news or events and we will get the word out. May you all have a happy and productive 2009!
17 December 2008
The mathematical groundwork was described more than forty years ago by Spencer Free and James Wilson at the old Smith Kline and French company, and came to be known as a Free-Wilson analysis. In a nice update of this work, Julen Oyarzabal and co-workers have applied this technique to the screening results of eight libraries consisting of several hundred compounds total. The molecules belong to five diverse chemical scaffolds (shown), and were tested against a variety of different targets, including a kinase, GPCRs, ion channels, and P450s.
For each library tested against each target, the authors asked whether the binding contribution due to a substituent Rx was additive, partially additive, or non-additive with the binding contribution of a substituent Ry. The mathematics get pretty intense, and the paper goes far beyond what I can summarize in a blog post, but the main conclusion is surprisingly encouraging: roughly half of all the data sets (10 of 19) show clear additive behavior, while another quarter (5 of 19) show partially additive effects. Only 4 data sets show non-additive behavior.
In many fields, a 50% success rate wouldn’t look too impressive, but in medicinal chemistry (in fact in much of chemistry in general), half-right sounds pretty good. The authors don’t further divide the non-additive data sets into sub-additive versus super-additive categories. In other words, the non-additive effects could well be due to synergy, the quality those of us pursuing FBLD ardently desire. But even if synergy is elusive, the paper suggests that you’ve got a better than even shot of producing a whole that is at least equal to the sum of its parts.
09 December 2008
The researchers started with the alanine “fragment” of the tetrapeptide Ala-Val-Pro-Ile (AVPI) and generated a virtual library of nearly 1400 alanine-containing derivatives. Molecular modeling narrowed this down to 15 which were then actually synthesized and tested by NMR to assess their binding affinity to a domain of XIAP; BI-75A1 was found to be a weak binder. Molecular modeling suggested that this new fragment (with a molecular weight just under 300) could in turn be “grown” to improve affinity, and after roughly 900 compounds were docked, 28 were then synthesized and tested. Of these, the most potent turned out to be BI-75D2, with a low micromolar dissociation constant in both NMR and isothermal titration calorimetry assays.
BI-75D2 exhibited improved stability in human plasma and S9 fraction compared to the starting peptide AVPI, as well as increased permeability. BI-75D2 also showed modest (16 micromolar) activity in a cell-based apoptosis induction assay, in contrast to the (inactive) AVPI peptide. Further biological experiments support the hypothesis that the small molecule induces apoptosis by binding to XIAP.
From a drug perspective, BI-75D2 still has a long way to go: it is a relatively weak binder, has a molecular weight greater than 500 Daltons, and contains several structural features that make a medicinal chemist squirm and a toxicologist squeal. Moreover, BI-75D2 has a fairly low ligand efficiency (LE), and this actually got worse as the affinity was improved. Nonetheless, as a chemical probe it may have value. It is also a demonstration of how fragment-inspired techniques can be used to attain novel molecules in an academic setting.
04 December 2008
Mekie started by asking (for a school paper) how widely FBDD is used.
Dan said widely. However, the current economic situation is seeing early technologies (those farthest from making money, like FBDD) getting axed. Exactly what Sunesis did :-(
Mekie followed up with the obvious question. Is it he cost of the biophysical techniques, such as X-ray/NMR/SPR that is the big problem. Would a cheaper technique be better
I jumped in with both feet and unafraid to piss anyone off by saying, "Nope. It's the chemist's hubris."
Then Dan, being the voice of reason, said it is more pragmatism over hubris. Too often weak hits ended up being complete crap and we are paying for that.
Tony G. joined in and said SPR may be the savior of FBDD (highly paraphrased. Go read his comments, quite cogent).
Then Pete joined the party and FBDD can negate the huge advantage in chemical space that Big Pharma has over small companies. He also agreed with Dan and expanded in that FBDD has not really been shown with membrane targets (which are only 50% of all the targets).
My comment about this is, the natural ligands are already fragments (Count the number of heavy atoms in serotonin.) He also says you need structural data and that is not forthcoming for membrane proteins. Hogwash says I. But we can debate that at a later time.
Finally NMR-soul pointed out that FBDD needs an early committment of resources when the chance of failure is the highest.
These were some excellent comments, well worth going in and reading. I think everyone would agree that FBDD practitioners (and can we come up with a cool name already) are also to blame for overselling what FBDD can deliver (I call this the NMR effect for obvious reasons.)
02 December 2008
20 November 2008
First up are a few fragment events at the CHI Molecular Medicine Tri-Conference extravaganza next February in San Francisco, CA. A pre-conference course on fragment-inspired medicinal chemistry will be held on February 24, followed by several fragment-based talks on February 25 and 26 (full disclosure: Teddy and I will both be presenting at this one).
Fragments 2009, held on March 4 and 5 in Alderley Park, UK (near Manchester), is organized by the Biological and Medicinal Chemistry Sector of the Royal Society of Chemistry. There is still space for posters, with abstracts due January 5.
And on April 7 and 8, Cambridge Healthtech Institute’s Fragment-Based Techniques will be held in sunny San Diego.
Know of anything else? Let us know and we’ll get the word out!
06 November 2008
This paper details the use of FLEXX and GOLD to screen >500k compounds against HisG, a potential tuberculosis target. In the end, two compounds showed bacteriocidal activity.
It is interesting to see docking actually working with fragments. It has always been my impression that you can get a lot of poses out of a dock with a fragment. With this paper I am proven wrong.
N.B. The clickable link may not work for everyone.
29 October 2008
Most of you are probably familiar with the concept of “click chemistry”, exemplified by the Huisgen cycloaddition of azides and acetylenes to form triazoles, and defined earlier this century by K. Barry Sharpless and colleagues. The idea, put very simply, is to react two molecules selectively and reliably to generate a product in high yield. The approach has obvious applications to fragment-based ligand discovery, and in fact Sharpless and co-workers demonstrated that the enzyme acetylcholinesterase can catalyze the formation of an inhibitor with femtomolar potency, starting from two fairly large and potent “fragments,” one containing an azide, the other an alkyne.
The notion of using a protein as a template on which to assemble an inhibitor dates back further than click chemistry. Huc and Lehn used reductive amination between aldehydes and amines in the presence of carbonic anhydrase to capture molecules that interacted more strongly with the protein than did the starting materials, and the technology even formed the basis of a company, Therascope.
In the latest example of this line of research, Roman Manetsch and colleagues find that the antiapoptotic cancer target Bcl-xL is able to catalyze the formation of an inhibitor from fragments sporting thioacids and sulfonyl azides; the inhibitor itself was previously discovered using different fragment-based methods at Abbott. The reaction appears to be relatively fast, and works even in the presence of a small pool of sulfonyl azides.
The paper, published this month in the Journal of the American Chemical Society, is a nice proof-of-concept study, but it does raise practical questions. First, the authors report the use of only six sulfonyl azides and three thioacids. These generally need to be custom-made rather than purchased; how much of a barrier will this represent to other practitioners? Once assembled, how stable will these fragments be in long-term storage? Finally, the product acylsulfonamide is a rather special entity not commonly found in drugs, and with a limited range of bioisosteres (indeed, it was originally employed at Abbott to replace a carboxylic acid). Still, the paper does provide an interesting - if less conventional - method of fragment-based lead discovery.
23 October 2008
By that I mean this
There is a link to buy it on the side of the blog. The book published on 17OCT2008 and is already getting great reviews. Here are a few choice ones:
"Fantastic dear, can you explain to me what you do again?" Teddy's Mom
"Cool." Teddy's Brother
"That's nice dear." Teddy's Wife.
WOW, with such enthusiastic support, the book will surely hit the New York Times Bestseller list.
Seriously, I think this is an excellent complement to the Erlanson/Jahnke book focusing on the real details of how to do FBDD. If you buy a copy, I will personally autograph it for you. If you buy it, and send a crisp, clean 20 $ bill to me, I won't.
16 October 2008
Some 250 of you had the pleasure of attending FBLD 2008 earlier this year in San Diego, one of the best conferences I’ve attended in my scientific career. The event brought a wide range of experts from a variety of experimental backgrounds. Held in a resort on a private island to encourage mixing, it felt like a Gordon Research Conference, but without the dorms.
The sequel will be held across the pond in beautiful York, an ancient university town with intact city walls, an 800 year old minster, and excellent restaurants and pubs.
Put September 21-23 on your calendar (with a special workshop on Sunday, Sept. 20), and submit your travel request now before your budget gets cut!
08 October 2008
Ever considered to use enzyme assays as a 1st line assay for fragment screening, then follow up with NMR or X-Ray AND SPR?This of course is the inherent (and apparent) tension in FBDD. Biophysicists (those rascally folk trained in such things as NMR, X-ray, SPR) want to perform their chosen technique. Medicinal chemists are no different, they want to make molecules. Biologists want to run compounds. Everybody wants to do what they are trained to do: management rewards doing your job. DUH!!! Credit is doled out by the dropper, so there is never enough to go around; we have been trained to grab as much unto ourselves as we can. The tension is not inherent in the science, it's imposed upon us by management [edited out my really nasty comment about managment].
Does the job!
Is it the belief of non-biophysicists that biophysicists don't find value in data generated by other techniques, or don't consider them of sufficient value? I have encountered highly dogmatic biophysicists...as well as highly dogmatic medicinal chemists, biologists, etc. My favorite quote, and absolutely real, "Why would I need fragments, I know how to get molecules into the clinic." Guess how many post-POC compounds that person had to their credit. Three guesses: first two are wrong, and the third should be less than 1.
I think the best FBDD practitioners (and shoot, we need some sort of really cool name for us) or agnostics. High quality data is high quality data, doesn't matter where it comes from. In fact, my answer to the commenter above is "Of course, when resources allow, multiple, orthogonal data is always the answer." FBDD should be method agnostic, something I have always preached. A rising tide raises all boats; credit should go to a team, not individual members. And YES everybody gets a pink unicorn in my world.
The researchers started with 3-methoxybenzamide, which was shown several years ago to inhibit the bacterial protein FtsZ and inhibit cell division in Bacillus subtilis, leading ultimately to cell lysis. FtsZ is a distant relative of the mammalian protein beta tubulin, a target for such famous anticancer drugs as paclitaxel.
The paper does not discuss the details of the fragment-based methodology used; hopefully this will be published separately. What we do know is that after some 500 analogs the researchers arrived at PC190723, which is roughly two thousand-fold more effective against B. subtilis as well as a host of staphylococci, including such nasties as multi-drug-resistant Staphylococcus aureus (MDRSA). Molecular modeling and mutagenesis data suggest that the compound binds to the region of FtsZ corresponding to the taxane-binding region of tubulin. The compound was also able to completely protect mice from an otherwise lethal challenge of S. aureus.
This is a nice story on several levels, as befits its publication in Science. First, it describes a new lead series against deadly bacteria. Second, it validates a new drug target and provides a new tool compound for exploring microbiology. And finally, it again demonstrates the power of fragment-based drug discovery to generate useful, novel molecules. Indeed, perhaps the fact that the fragment-origins of PC190723 are merely a side note as opposed to a central focus of the publication shows that the technique has become main-stream.
26 September 2008
1) The protein structure is correct.
2) The structure of the ligand and its interactions with the protein are correct
3) The protein–ligand structure is relevant for drug design
“While these assumptions seem perfectly reasonable at first sight,” the authors note, “they are not all necessarily true.” The review then provides examples where these assumptions went awry, as well as the lessons that can be drawn from these mishaps.
The fact that crystallography can be misleading should not come as a surprise to anyone who has worked in drug discovery, but what makes the article worth reading is the range of examples. I should say that I’m a huge fan of crystallography and have found it to be very valuable. Perhaps because of this, it is all the more distressing when it leads me astray. In my experience with fragment-based drug discovery, this has most frequently happened with assumption #3; it is not uncommon to find a lovely fragment making appealing interactions with the protein, but to still have difficulty measuring any affinity, much less improving it.
Anyone have stories or thoughts to share?
14 September 2008
Alex's paper looks back at all of the fragment papers and looks at what was the starting point, where it went, etc. I took his data and applied my own filter to it (what one former colleague termed the ZOF, the Zartler Optical Filter).
The following two tables are from Chapter 2 of the upcoming book, on designing a fragment process.
This data is looking at the origin of the type of fragment strategy employed and the main method used to support it moving forward. Linking/assembly is exactly what it sounds like, attaching different fragments (zinc binding group and biphenyl a la Abbott). Anabolic is the logical growth of a fragment to a lead-like/drug-like molecule. Other could not be classified from Alex's paper.
There were roughly the same number of projects that used either anabolic or linking. However, the anabolic method would appear to be better at maintaining or increasing ligand efficiency.
I also looked at NMR vs. X-ray vs. Other methods in terms of projects that maintain or increase LE. NMR and X-ray have the same number of projects (whose sum is equal to the total of Other). It does appear that NMR is better than X-ray in maintaining LE.
Here is the firebomb: With the well documented history of success, sufficient data to say that the anabolic approach is superior, and the NMR approach superior to X-ray, why is it that large pharma seems to be so slow in adopting what is an obviously successful method?
13 September 2008
Sareum’s platform focused on the crystallographic discovery and recombination of fragments; Galapagos is planning to merge these capabilities with their BioFocus DPI contract services group.
The price? Just £ 553,000, or a little more than $ 1,000,000 at the time of the announcement.
What conclusions can be drawn from this acquisition? On the one hand, clearly Galapagos feels the technology has value. On the other, a million dollars doesn’t go far these days; it would be difficult to put together the platform Sareum has been building since 2003 for this sort of money.
Obviously a single data point can not lead to a whole theory, but it does spawn many hypotheses. What does this mean for service-based business models? For valuations of European vs US companies? For the value (fiscal and scientific) of fragment-based drug discovery in general?
25 August 2008
At Sunesis, we used custom-built, disulfide-containing fragments for Tethering, but of course most techniques aren't limited to disulfides.
So everyone, does your company sell fragments? Now is your chance to get some free advertising!
Or have you purchased fragment libraries? Did you like them? If not, now is your chance to get some free complaining!
22 August 2008
For some Friday fun here are the last five songs on my IPOD:
Miss Freelove '69 by the Hoodoo Gurus
Don't Feel Like Dancing by Scissor Sisters
Loving You by Paolo Nutini
Cursum Perficio by Enya
Rollin' by Limp Bizkit
OK, I admit, I am nothing if not eclectic.
What are you listening to?
"Man is the measure of all things: of things which are, that they are, and ofwhich the first part is the part most of us know.
things which are not, that they are not"
It is clear that FBDD is "HOT", and I have been struck by how many companies are doing or want to do NMR as part of their FBDD. This is surprising considering that many pharmaceutical companies have been through the ebb and flow of the 3 stages of NMR disease: 1) structure will revolutionize drug discovery (1992-1996), 2) NMR screening will solve the HTS problem (1996-2004), and 3) we have SO learned from out mistakes, trust us THIS time (2004-). As James Bond said, "Once is happenstance, twice coincidence, and three times is enemy action."
I lived through stage 2 and the resultant NMR-ectomy at a Big Pharma. The driver for the round-filing of our group was "business decision", in other words "we have no idea what value you add and sheesh, those silver cans are expensive to upkeep." Obviously, the value of technologists, especially at big companies, is tough to quantify. It is even harder if you don't fully understand the technology or how it is applied. I asked one of our senior management how do you quantitate the contribution of technologists (Computational, Structural Biology, etc.) to a project. His answer was wholly unsatisfying, and state of the art: "We will see over time [thinking to myself at the time, what sort of timeframe?] that projects you are involved with are more successful."
Very Protagoran, don't you think?? But not very satisfying to the technologist.
So, with an increasing level of technology commensurate with an increasing level of FBDD in industry at both the Big and Small pharma level, I pose the question: "What is the value of the technologist?"
18 August 2008
A high-throughput screen against the diabetic drug target fructose-1,6-bisphosphatase (FBPase) identified a small thiol with a low micromolar IC50. FBPase is a homo-tetramer, and when the crystal structure of the HTS hit bound to the protein was solved, the researchers found that the thiols had oxidized to form disulfides: two dimers bound to each tetramer, with one phenyl sulfonylurea bound in each of four binding sites. Subsequent analysis of the screening hit revealed it to be contaminated with about 5% of the disulfide, which had presumably formed by air oxidation; this was the source of the inhibition in the HTS assay. In other words, the screen had identified linked fragments.
With this structure in hand, the researchers synthesized a series of dimeric molecules connected by various linkers; they also replaced the aniline with meta-substituted phenyl moieties. Clear linker-length dependence was observed, with the shortest linkers showing no activity, while the molecule with the six-carbon linker shown has an IC50 of 17 nM. Crystallography revealed that this molecule binds in a similar manner as the disulfide, although the linker itself showed some disorder. Gratifyingly, when the molecule was cut in half, the resulting monomer was found to bind much less tightly, with lower ligand efficiency. The dimeric molecule binds with a free energy of 10.6 kcal/mol, almost 2 kcal/mol more than would be predicted by simply adding the binding energies of the monomers.
Of course, the molecule is far from a drug (although it does show an impressive 100% oral bioavailability in mice). Nonetheless, it illustrates one of the key advantages of fragment-based ligand discovery. Fragments linked together can really be more than the sum of their parts.
11 August 2008
There will be many interesting talks given on FBDD.
In Session 1 (Novel Lead Finding Approaches) two of three talks will be on FBDD (SGX and Roderick Hubbard from York/Astex)>
Session 2 (Chemistry Strategies in Reducing Attrition in Drug Discovery) will have a talk from Astex
Session 7 (FBDD, presented jointly by ACS) has three outstanding speakers and should be very interesting. If you haven't caught Alex Alex's paper on the history of FBDD, go and find it in Current Topics in Medicinal Chemistry.
Additionally, there will be a forum entitled : "How to close the gap between academic training in medicinal chemistry and industrial reality?" I think this is a particularly relevent topic for any field and not just medicinal chemistry.
Coming up in 4-5March2009 is Fragments 2009. This is a call for abstracts and to make the general populace aware of the meeting. And of course, what an excellent chance to meet Associate Editor Vicki Nienaber.
We will be post further meeting/symposia notices as we get them.
06 August 2008
As the money markets dry up, more companies will seek to cut their running costs, to make their cash reserves last that bit longer. Biotech companies (few of whom post profits) will be particularly at risk from the "credit crunch". Products, early revenues and profits are now the order of the day. In our sector, early licencing candidates will be key, and companies such as Vitae, Astex, Incyte, Onyx and OSI, with optimized candidates in hand, will be the ones to watch.
05 August 2008
Starting with just 500 fragments, crystallography allowed the researchers to identify more than 30 fragments that bound in the ATP-binding site, all of which made at least one hydrogen bond to the so-called “hinge region” of the protein. Three of these fragments were optimized using structure-based design and medicinal chemistry, with the most successful yielding AT7519.
The figure shows the progression of the series, starting from the initial fragment, along with the IC50s and the ligand efficiencies of key milestones. Some notable decisions included replacing the indazole moiety with a pyrazole, which resulted in a 30-fold drop in biochemical potency but did not notably reduce the ligand efficiency, and the replacement of a fluorobenzene moiety with a piperidine, which led to a loss in biochemical potency but an improvement in solubility and cell potency. AT7519 showed 86% tumor growth inhibition in an ovarian mouse xenograft model when dosed IP at 7.5 mg/kg. The full paper is well-written and provides an elegant example of taking a fragment all the way to a clinical compound.
02 August 2008
The editors of practical fragments have decided that we will do a weekly update of the Fragment literature. We may make it a book club type of thing also where there is a precis of the paper and some discussion around it.
We are also keeping an ongoing Endnote file for FBDD references. This is generated in EndNote X1, and unfortunately we are finding out that X1 doesn't translate well (for example into EndNote 6). So we are posting the library as a .enl file and as an .xml. We can also do .txt, so we hope that this helps.
Of course, after saying all of this, I can't figure out how to add a non-video/audio file to blogger. Any help would be appreciated. Until then, people can email me and I will send it on to them.
30 July 2008
How does this affect fragments? Hoffmann-LaRoche in Switzerland published an early example of fragment work on DNA gyrase way back in the year 2000 (using a technique called needle screening), and recently Roche Palo Alto has published some very useful guidance on how to identify - and avoid - screening artifacts in SPR (see glossary, 28 July). Practical Fragments wishes the Palo Alto folk the best of luck, and hope they put their considerable skills to good use wherever they land.
On a happier note, the same week the Roche-Genentech deal was announced, newborn Zenobia Therapeutics announced that it had commenced operations. Founded by Vicki Nienaber, who published what I believe is the first demonstration of crystallography-based fragment lead discovery while at Abbott (also in 2000), the company plans to pursue partnerships as well as its own work on neurological and muscular degenerative diseases. The company's motto is "fighting to cure disease, one fragment at a time," and we look forward to watching them grow.
28 July 2008
I promise you this is not a complete list, nor will it be necessarily alphabetical.
Abbott: Pharmaceutical company considered to be the pioneers of Fragment-based Drug Discovery
CADD: Computer-aided Drug Design. This is a "design" vs. a "discovery" method.
FBDD: Fragment-based Drug Discovery. An ExecDir I knew preferred Discovery over Design for odd reasons, which in typical fashion I forget here.
FBLD: Fragment-based Ligand Discovery. This actually makes more sense, because we are looking for ligands to targets, which eventually will be turned into to drugs. This is to create more of a contrast to standard HTS (see below) which screens for drugs.
Fragment: A chemical structure smaller than the final drug.
IP: Intellectual Property, as in there is none for fragments (That's for you David.)
ITC: Isothermal Calorimetry. Proof that you really needed to take that thermodynamics course in college, and you probably should have taken one in grad school.
Ligand: Chemical moiety that binds (or mostly doesn't bind to target).
NMR: Nuclear Magnetic Resonance Spectroscopy Method which uses the quantum nature of nuclear spins to generate data on the binding and structure of ligands and target.
SBDD: Structure-based Drug Design. I think this is more acceptable to say "drug design" because of inherent use of CADD. There have been more Nobel Prizes for NMR than X-ray.
SPR: Surface Plasmon Resonance, a.k.a BiaCore. Although this is more Xerox than anything else. The method is SPR, the maker of the machines is BiaCore, now a wholly owned subsidiary of GE Healthcare. Of course, just like Xerox and copy machines, there are other manufacturers of SPR equipment.
Target: That to which one wishes to bind a ligand to modulate some biochemical activity in order to achieve a pharmaceutical effect, hopefully with clearly defined IP. Targets can be proteins, nucleic acids, or any other biological entity.
X-ray Crystallography: Method which uses the wave-particle duality of atoms to generate data on the binding and structure of ligands.
Two easy ones:
Shuker, S. B., Hajduk, P. J., Meadows, R. P., and Fesik, S. W. (1996) Discovering High-Affinity Ligands for Proteins: SAR by NMR, Science 274, 1531-1534.
This demonstrates a start to finish process for prosecuting fragments. It is especially important in that it also establishes the primacy of having binding information to help drive medchem decisions.
Hajduk, P. J., and Greer, J. (2007) A decade of fragment-based drug design: strategic advances and lessons learned, Nature Reviews Drug Discovery 6, 211-219.
This paper compares and contrasts FBDD vs. more traditional lead-like, HTS screening. It clearly demonstrates the advantages of FBDD in generating high quality hits with a better chance of progressing.
Now you all...
26 July 2008
I thought I’d highlight an excellent article on fragment-based lead discovery that appeared as the cover story of C&EN this week.
The story discusses the background of the field, current practice, and very recent industry developments (and I’m not biased for being quoted!).
Also, anyone want to go on record as to when we can expect the first fragment-derived drug to reach market?Dan
24 July 2008
After some discussion, we have settled on how we are going to utilize this blog. First off, we are going to focus on fragments. PERIOD. We are working with the Structure-based Drug Design blog to have some synergies and limit overlap. As other blogs, forums, etc. come on line we will link to them.
So what about the format for this blog? Some ground rules first:
1. Assume anything you say here is disclosed. There is no confidentiality.
2. As my Latin teacher used to say, "The only stupid questions is the one you never ask."
3. As travel is being restricted across the board, virtual discussions will be the primary way to speak with colleagues. Utilize the tool.
4. This is non-commercial; blatant advertising will get you banned. Companies are of course allowed to share discoveries, as is anyone else.
5. This list is subject to change at any time.
As to format and content, we are planning on having a few "associate editors" who will post entries. Each associate editor will be a subject matter expert in a given general area. They will not necessarily be writing our content; our plan is for you the readers of the blog to write it. If you have a question, write it up and submit it. There will be links to the side to do this.
Appropriate content will be:
Questions of specific and general interest?
Other things I haven't thought of.
Questions of content that need to be discussed are:
Changes in company strategy (this site is closing, or that company is axing this group, etc.)
Job openings or positions wanted.
In order for this lively experiment to work, we need it to have engaged, interested readers. Please, let me and the other editors know what else we can do to make this work for you.
If you are interested in being an associate editor, we still have a few openings. Just let me know.