But Pfizer was touting Exubera as a >$2 billion/year product, One smaller company (Mannkind) is stil plugging away with inhaled insulin but the biggere ones bailed out post-Exubera, although not at such cost

The funny thing is, we have a bunch of ex-Merck people here at the institute - and apparently they continue to be tremendously important and they take themselves very seriously even after they have left Merck.

Is there any real hell in this earth? I would say yes, there are hells all over the world. The kings or the masters in these hells are human beings---- maybe that is why human beings were driven out of the Garden of Eden. According to the report which was worked out by a British animal protection organization, we know the cruel fact that exists in the Wickham Laboratories. There are lots of rabbits locked in the small cases which are absolutely smaller than the rabbits’ bodies. And according to the investigators’ photos, we could see several little white mice had been left in the case on a corner of the lab, they were waiting for the coming of Death but they could not do anything to stop it. All these things are done by human beings, the only race in this world thought they have something names humanity. I believe that the lanyard">http://www.ybuw.com/Lanyards/">lanyard the staff wear are bloody. And according to the photos, we could see the innocent eyes of those rabbits and mice. They do not what will happen to them, they do not know how to escape from these cases, and they might only have the feeling of pain and have to suffer these things in silence. What are those examines for? Maybe some of them are taken for testing the anti-wrinkle cosmetics that only female human beings would use. Why should they suffer pain for the lady they have not known? And we could imagine that how many blood or life would be devoted for one simple bottle of anti-wrinkle cream. And I think that is not the most horrible lab, or we should call it a hell, in this world. The worst ones are located in China, in these hells they pick up bear galls from bears alive and keep them in the little cases in the dark rooms. And in Japan, people even eat the dolphins alive as what they called sashimi. Face to the earth like this, even God would close his eyes and turn his back to us, I think.

The "New Merck" had a lot of hoopla going on this week, all about synergies and how great we (ie legacy Merck) are and how great the pipeline is. But the interviewing of SP people starts next week. And some have already been shown the door. Who needs legacy SP folks when the Merck folks are all knowing and all powerful? Just ask them - they will tell you how important they are.

I don't think the cost or lung risks made inhaled insulin workable - it didn't fail as in "was not a blockbuster", it failed as in "cost multiple billions to market and develop and made $12M (m, not b)". A smaller inhaler would help compliance but wouldn't remedy the cost issues, and with other effective methods for diabetes control, insurance wouldn't want to front either the extra cost or the coverage for potential lung damage. The cancer rumors were just gravy on the Titanic. It might work as a niche product, but the development required to make it an effective niche product and the cost the development would impose on end users is probably a showstopper.

Having an inhaler the size of a bong was the least of Merck's worries?? Try reading it again? It was Pfizer. The general idea was a good one, gain higher compliance by people that hate needles. The "Bong" I beleive what really was the issue. Older folks didn't want to carry that thing around. The possibility of lung damage/cancer was probably too much of a risk for Pfizer, with so little return. I have read that the other players have a much more convenient inhaler. I personally never believed this to fit in the blockbuster drug model of Pfizer. Too Much wishful thinking and then when it didn't live up to expectations turned into a bust. Type I Diabetes is much better regulated with injections and proper monitoring. Insulin pumps and monitoring have been a life saver for many. Wish these were available 40+ years ago. Might have made a really big difference in my uncles life. Born with type I he didn't have many options. All he could do was watch his diet and use injectable insulin on a schedule. Was not easy to monitor blood sugar back when he was a child. He ended up dying from complications of the condition in his later 40's in the end. The damage was done. So - although this was a bust in the Pfizer scheme of things - it may still have its place as a niche product. Emergency inhaler easy to carry, when you need it and are away from your "kit" perhaps? Less stigma assocated with using inhalers (as apposed to "Bongs"!) than with the need to use needles in public. Look at ashma sufferers. Just something to think about. Not all inovations have to be $16B sellers!

"I know I would *definitely* want to know if the author of a paper which is favorable toward intelligent design is a board member of the Discovery Institute." Why? Do you give an argument for ID more credence if it comes from someone *not* affiliated with the Discovery Institute? I don't. As The Chemist said in #8, "Either the research stands on its own - or it doesn't."

I love it. The chemists who formulate the highly toxic compounds in expensive consumer products are complaining about the laywers making money off of the MSDS's used as evidence in the wrongful death suit. Are you a comic or a chemist Mr. Lowe?

Derek, the MSDS is more hazard based than risk based, so they may scare you more than you think they should. It does not rally take 'extensive' exposure to silica to cause silicosis. I find that it is not until they read the MSDS for clay, that art teachers understand the relationship between dry sweeping clay dust and silicosis. Thats when they take the sand paper away from the student and get that seam off of the ceramic mug with a sponge instead.Thats when they switch to ordering moist clay bodies instead of bags of dry clay. Look at that, useful MSDS's! I am not suprised that chemists find MSDS's useless.Just google laboratory injuries in schools and see how many chemistry teachers have put themselves or their stuents in the hospital for just not getting the importance of MSDS's and actually taking a moment to read one once in a while. I found your take on MSDS's quite silly. I would imagine that occupations such as those involving sandblasting, cramics, cement manufacturing, and others where respirable silica (from plain ole beach sand) is an issue might find your take on those useless MSDS's downright dangerous. Hey did you read about the chemists at MIT who recently set a boat on fire playing with sodium? Water reactive? Who knew!I must admit, without chemists who think like you, us safety folks would be out of a job. You received your Phd from Duke? Is that not where Dr.Woodhall Stoppford and his staff produce all of the MSDS's for all of the art and creative matrials used by children in the US? why dont you stop by his lab and remind him how useless his MSDS's are? Who was the chemistry chair at an Ivy league school who killed herself by wering the wrong gloves while working with dimethyl mercury? I think her last words were, MSDS? Bah humbug!

Inhaled insulin that costs three or four times as much as the injected version, with a likelihood of lung damage and a small (maybe very small) chance of lung cancer? If a lot of things were different, than inhaled insulin could have been a good idea, but, this...um, no. Having an inhaler the size of a bong was the least of Merck's worries - heck, if they had reinforced the inhaler, you might have had an effective self-defense weapon.

Inhaled insulin is NOT a bad idea. Having an inhaler the size of a bong is, though!

25: Actually GSK had run a screen for Sirt1 inhibitors, but everything they got from the screen turned out to be artifacts. That's why Moncef and Patrick wanted to buy Sirtris, b/c they supposedly had what GSK had been unable to get internally. Unfortunately, Moncef listened to the Sirtris people rather than the GSK scientists who did the due dillegence. That is one of many reasons he should be fired.

One more experience i would like to add. Since my starting material (nitro aromatic compound) for Pd/C hydrogenation was soluble in DCM, i used to take mixture of solvents DCM and MeOH for reaction, which worked very well with almost quantitative yield.But,when i did the same reduction of nitro to amino, in solvent mixture of CHCl3 and MeOH, i had very less product and more impurities(4 close TLC sopts besides the product). I had experienced this poor yield/side reactions three times (using different starting materials, but always a nitro aromatic compound). I could not figure out what could be the side reaction. Can any one suggest?

backing up comments #21 and #23. I had the same experience that on small scale (mg scale), no problem of fire. On bigger scale (grams scale), there was fire two times. Even weighing Pd/C directly in a beaker containing MeOH, catches fire. Best way in big scale is to inertise the flask, weigh first Pd/C, then wet it with solvent like EtOAc. Also, i had found whenever the Pd/C is fresh, the chances of fire is more. On prolonged storage, it probably becomes wetter and so no problem of fire.

14: I liked that paper, and at least the molecules were simple enough that they might be useful if they can be made rapidly. TaxolXXXXXpaclitaxel wasn't ever going to be producible in that way, and analogs (other than at the amino acid side chain) were probably not going to be useful either. I think that resveratrol and its derivs might be useful (and the sirtuins might be useful, too, at least to understand), but buying a company for a lot of money with (apparently) not much understanding of the fundamental biology seems like a problem. Do you think Amgen spent $720M to develop their assays and get useful data on resveratrol? If Amgen was able to develop that capacity, why couldn't GSK? (Part of buying the company - most, I assume - is the IP, but if the IP isn't relevant to the desired activity, well...)

Did you see this "Larger Merck says merger will actually increase R&D efficiency" (http://www.pharmatimes.com/WorldNews/article.aspx?id=16862&src=EWorldNews)? I laughed.

this is just to let you know that after the merger the people are let go during "Thanks Giving" or "Christmas" break.

Cliff, And exactly what are you going to target here using resveratrol as your lead?

Tachi bought some cr*p too. His final big deal was a particularly poor effort...

#8...... You are right. Those two are responsible for destroying a great R&D organization. The Sirtis deal is just one example of many, many poor decisions driven by their own personal agendas. GSK is doomed.

ZA: Zambon (Italy)

#19 and #20 I started tongue-in-cheek and ended serious. Serious: Any non-selective lead needs more interactive groups with the correct spatial orientations to improve selectivity for the desired receptor, and or conformational restrictions with the same objective in mind. Design some suitable scaffolds, put in some extra and promising (H-bonding, etc) receptor binding groups (based on likely receptor interactions, where receptor structure is known/ligand receptor binding info is available, or empirically where there is limited info) and hey-presto! we have a med chem project. Start by learning how to synthesise the b---rs, preferably a few months before screening of newly syntheised compounds is initiated. Don't forget to check patents and lit and throw out all the worked out 'design spaces'. With apologies to all serious medicinal chemists.

"This is a fabulooous opportunity for medicinal chemists to create a potent *clean* analogue of *dirty* resveratrol." I think one of the biggest lessons from the last 20 year of NP synthesis is that many, many NPs cannot be optimized in med chem fashion. Truncations sometimes work, but in general for molecules like resveratrol which thumb their noses at Lipinski, the observed activity is a global phenomenon that we really can't *begin* to deconvolute.

Are you being facetious cliff and I'm missing the joke?

Maybe resveratrol does not act via the SIRT1 pathway but there appear to be advantages of knocking down SIRTi in the liver SirT1 knockdown in liver decreases basal hepatic glucose production and increases hepatic insulin responsiveness in diabetic rats Derek M. Eriona,b,c,1, Shin Yonemitsua,b,1, Yongzhan Nied, Yoshio Nagaia,b, Matthew P. Gilluma,b,c, Jennifer J. Hsiaob, Takanori Iwasakib, Romana Starkb, Dirk Weismannb, Xing Xian Yue, Susan F. Murraye, Sanjay Bhanote, Brett P. Moniae, Tamas L. Horvathd, Qian Gaod, Varman T. Samuelb and Gerald I. Shulmana,b,c,2 PNAS July 7, 2009 vol. 106 no. 27 11288-11293