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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Thallium Poisoning? In This Day and Age? | Main | Drug Problems: A Diagnosis »

February 10, 2011

The Top 200 Drugs

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Posted by Derek

If you haven't seen the "Top 200 Drugs" posters, available as PDFs from this group at the University of Arizona, then give them a look. It's good to have this information in graphical form, with chemical structures attached.

One thing that stands out as you browse through the table is the number of compounds that make you say "Hold it - that's a drug?" I think that's one of the most valuable things about the poster, actually. It's worth seeing how simple some useful compounds are (valproic acid, anyone?), or what functional groups have made it through. The next edition of the poster will surely feature Gilenya (fingolimod), whose structure baffles and offends almost every chemist at first glance.

It's a dose of humility, seeing these things. And while it's true that we get regular doses of humiliation in the research business, our pride is pretty resilient, too.

Comments (45) + TrackBacks (0) | Category: Business and Markets | Drug Industry History


COMMENTS

1. J-bone on February 10, 2011 9:06 AM writes...

I didn't know Njardarson left Cornell.

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2. Anonymous on February 10, 2011 9:39 AM writes...

Similac - easily my favorite structure.

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3. Anonymous on February 10, 2011 9:40 AM writes...

Similac - easily my favorite structure.

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4. NoDrugsNoJobs on February 10, 2011 9:51 AM writes...

Great Post Derek, its a pretty neat idea! I used to spend my spare hours in grad school just flipping through the Merck index looking at the different structures. I don't know why I did that but I did!

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5. glinkst on February 10, 2011 10:20 AM writes...

These charts are great and say a lot about what is happening. 10 of 22 top drugs are biologics , compared to about 2 or so of the top 40 from 2005. No one takes a biologic unless they have to, so they usually fit under the definition of "unmet clinical need".
G

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6. milkshake on February 10, 2011 10:24 AM writes...

fingolimod is not that bad. Had I not seen it before (for example, if a beast like this one came up from HTS), my first concern would be nonspecific interactions and surfactant-like action on membranes, which would be easily addressed by looking at hemolytic properties.
When you look at the history of of its development from a natural product, it is actually a great example of drug design: the molecule is wonderfully cheap and simple to make

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7. Anonymous on February 10, 2011 10:30 AM writes...

Derek - I am glad to see this post. It’s way too late for me, unfortunately. Back when I was employed in Big Pharma and obesity and metabolic diseases was a fad, I validated a screen for hypolipidemic agents using cetaben, the structure here:

http://www.caymanchem.com/app/template/Product.vm/catalog/10007171

I presented the findings to the med chemists and was chased out of the room tail between legs. It’s not like I asked them to consider SAR around cetaben, but that they wouldn’t even consider a screen validated against such an ugly compound. One can presume I might find a different reception today?

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8. Anonymous on February 10, 2011 10:43 AM writes...

#1--If you look at his CV it seems that he didn't get tenure?

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9. Will on February 10, 2011 10:51 AM writes...

Maybe I'm just ignorant, but it was surprising for me to see 4 antipsychotics in the top twenty-one, and only 1 SSRI

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10. Anonymous on February 10, 2011 10:53 AM writes...

@ #1, He didn't get tenure at Cornell.

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11. Plutonium Grandad on February 10, 2011 10:53 AM writes...

I wonder if Abbott's Similac plant looks like the one in Georgia where they make Cabbage Patch Dolls. Is that a photomicrograph? How do they get the eyes on?

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12. luysii on February 10, 2011 10:56 AM writes...

Don't forget that valproic acid was found purely by serendipity. Drugs for epilepsy have to be lipid soluble to get into the brain. Valproic acid is mostly hydrocarbon and was used as the lipid vehicle to dissolve other drugs.

Further showing how little we know, gabapentin was designed to look like (and mimic) gamma amino butyric acid (GABA), a major inhibitory neurotransmitter in the brain. Its just GABA with a cyclohexane ring on the beta carbon. Its mechanism of action has nothing to do with GABA.

The problem with rational drug design, is our very incomplete understanding of cellular biochemistry and physiology.

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13. RB Woodweird on February 10, 2011 10:56 AM writes...

Great poster. I have only one question: How does one pronounce Njardarson?

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14. Rhenium on February 10, 2011 11:05 AM writes...

Best recruiting tool ever...

I put these posters up outside the intro chem labs, students and parents alike are "I'm on that one, grandma is on those too, cousin Bill (hushed whisper) is on those four or five"... etc

Must be something about the ubiquity of meds coupled with good design ideas and small molecule (mostly) chemistry.

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15. sigma147 on February 10, 2011 11:08 AM writes...

I'm not so sure about the diagnostics on the list (diabetes tests). Not really drugs in the minds of most, I'd say...

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16. MTK on February 10, 2011 11:11 AM writes...

In the neverending debate about outsourcing R, I wonder how many of these, both in quantity and revenue generated, were discovered by in-house efforts at Big Pharma vs. outside Big Pharma.

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17. anon on February 10, 2011 11:15 AM writes...

Still amazed that lovaza is a prescription drug.

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18. InfMP on February 10, 2011 11:46 AM writes...

People keep telling me not to use sulfur, but look at the top drugs on that list. They all have it/

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19. Cornellian on February 10, 2011 1:24 PM writes...

The top selling drug posters are published as a teaching tool and can be cited as:

McGrath, N. A.; Brichacek, M.; Njardarson, J. T. J. Chem. Ed. 2010, 87, 1348.
DOI: 10.1021/ed1003806

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20. barry on February 10, 2011 2:21 PM writes...

I can't be surprised that the top of the list is rich in drugs for which the course of treatment is decades long (HMGCoA reductase inhibitors, anti-depressants, anti-psychotics...) but I'm flabbergasted to see Zetia making billions. The clinicals were run and it did not decrease morbitity/mortality. To pursue the surrogate endpoint of reducing circulating cholesterol (or tweaking the ratio of HDL/LDL) when it is shown to not correlate with morbidity/mortality is scandalous.

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21. KevinM on February 10, 2011 3:21 PM writes...

What do the colored squiggles mean on a drug like remicade? Everything else I can follow, but I've never seen that notation before. Even wikipedia fails me.

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22. -GiMP- on February 10, 2011 3:29 PM writes...

be interesting to have patent expiration dates on each box too...

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23. Mark on February 10, 2011 3:51 PM writes...

#21

The colored squiggles are beta sheets. The colors indicate different protein domains (I think).

Mark

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24. Wagonwheel on February 10, 2011 3:58 PM writes...

Colored squiggles indeed! I love that, you've come to the right forum to derogate biologics. Remicade is a great drug though...small molecule or not.
This poster is a great motivational tool, it should be hung somewhere on the wall of every med chem department, long live chemistry and intelligent drug discovery!

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25. Anonymous on February 10, 2011 4:12 PM writes...

The colored squiggles are beta sheets. The colors indicate different protein domains (I think).

Aren't the squiggles a-helices and the other ones that are basically arrows the B-sheets?

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26. barry on February 10, 2011 6:50 PM writes...

why do Adderal (#104) and amphetamine (#168) get independent entries? Shouldn't they appear together (and ranked higher by dollars/yr)?
$1.76 billion would put it at #58 overall

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27. aldehyde on February 10, 2011 7:51 PM writes...

because adderall is a mixture of amphetamine salts but "amphetamine" is just dextroamphetamine.

the pdf is down, I guess you've overloaded their site. Any chance of a mirror?

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28. barry on February 10, 2011 9:16 PM writes...

re #27
the presence of an impurity (in this case 50% as the enantiomer) in one formulation doesn't seem reason enough to count the drug twice (assuming only one enantiomer is pharmacologically relevant)

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29. non-pharma chemist on February 10, 2011 9:35 PM writes...

@ milkshake: it sure looks cheap and simple to make. If you've been paying attention, Novartis recently released their pricing - I can't remember exactly but it was going to cost 40,000$ (or about that) per year! If I had MS, I'd make it myself...

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30. researchfella on February 10, 2011 10:02 PM writes...

The chart is very nice, but be aware that it's not completely accurate. The data source cited for the chart is IMS Health Incorporated, and they apparently have gaps in their database. That might be caused by some pharma not disclosing some sales figures. For example, where are those Bayer moneymakers Cipro and Nexavar (sorafenib)?

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31. Anonymous on February 10, 2011 11:01 PM writes...

200 drugs is a significant chunk of the pharmacopoeia of FDA-approved drugs as there are only about 1,300 such molecules.

Remarkably, these 1,300 drugs are directed against only about 250 different targets in humans (although the targets of a significant number of drugs are ill-defined).

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32. KevinM on February 11, 2011 12:29 AM writes...

@24
"Colored squiggles indeed! I love that, you've come to the right forum to derogate biologics."

wtf? Just asking a question, how on earth was I "derogating biologics" when I have no clear idea what specifically biologics are? I looked at the charts and saw things I could understand and things I couldn't. A pointer on "Biologics for Idiots" would be helpful for those of us who look at some of the charts and can best describe them only as "colored squiggles".

Some of us here have only 1 or 2 semesters of undergrad chemistry. If Derek doesn't want us posting here, he should tell us.

@23 @25 Thx. Beta sheets are beyond my ken, but I appreciate you trying to show me where to look.

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33. Anonymous on February 11, 2011 1:26 AM writes...

I was amazed at how many tetrazoles were on the list, are these acid bioisosteres added for formulation purposes or are they crucial for binding?

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34. Pete on February 11, 2011 3:41 AM writes...

This poster illustrates the fiction of representing 'drug space' as a single contiguous region in 'chemical space'.

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35. Bjonnh on February 11, 2011 4:51 AM writes...

Here is the link as their database is suffering :
http://cbc.arizona.edu/njardarson/group/sites/default/files/Top200PharmaceuticalProductsByWorldwideSalesin2009.pdf

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36. anon the II on February 11, 2011 7:58 AM writes...

To Anonymous #33

There are a lot of tetrazoles on the list because there are a surprising lot of A2-antagonists. The tetrazole was used as a carboxyl replacement for better ADME while retaining the activity of the carboxylic acid. I noticed an A2-antagonist with a carboxylic acid on the list. Maybe it's for IV.

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37. Anonymous on February 11, 2011 8:30 AM writes...

KevinM, take comments here with a grain of salt.

alpha helices and beta sheets are different structures that proteins can adopt. To answer your question more simply, the colorful squiggles and arrows represent large proteins (hundreds, maybe thousands of amino acids long).

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38. Hap on February 11, 2011 11:21 AM writes...

#32: See this for Wikipedia's explanation of ribbon diagrams in general. They're used for big protein structures to show how the long chains of amino acids fold and fit together. Because there are generally so many atoms, the level of detail of the structures is much lower than for small molecule structures (erythropoietin, for example, in Amgen's (Aranesp)and Johnson and Johnson's drugs, has about 150 amino acid residues, so > 1000 atoms), and the people using them are generally interested in their general shapes and substructures rather than in their atomic-level structures.

The broad Y-shaped line drawings are for antibodies, I think.

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39. Cornellian on February 11, 2011 3:14 PM writes...

@30
Unfortunately there are not many sources for sales information available. This is the same source that Forbes uses in their articles.

http://www.forbes.com/2006/03/21/pfizer-merck-amgen-cx_mh_pk_0321topdrugs.html

There is an alternative data source that the authors used in previous years if you are interested.

http://drugtopics.modernmedicine.com/Pharmacy+Facts+&+Figures

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40. Plutonium Grandad on February 11, 2011 3:35 PM writes...

KevinM

I don't think Wagonwheel was being too serious...

#37 is right, after you've visited this blog for a while, you realize that many comments here are tongue-in-cheek.

I don't have the slightest idea about half the stuff discussed here, but I love Derek's writing style.

By the way, I didn't know what those squiggles were either.

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41. larry on February 11, 2011 7:29 PM writes...

Interesting chart but the structures are wrong for tenofovir which shows up in #36, 39 and 193. In 39, the structure includes the correct pro-drug moiety but has the main structure wrong. The other two instances show the correct structure but without the prodrug segment that makes it an actual useful drug.

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42. TFox on February 14, 2011 1:00 PM writes...

Acetaminophen seems to be on there twice, under two different names (#181 and #188).

What I'd like to see is a list of drugs ranked by estimated net benefit to society. Obviously there are difficulties in making those estimates, but it'd help differentiate between "most important (to society)" drugs and "most profitable (to pharmaceutical companies)" drugs.

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43. Hua zhang on April 12, 2011 11:15 PM writes...

Dear sir:
We are chemical company from china.could you please send us a copy of top 200 drugs.
thank you
Hua

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44. Yixian-Li on May 17, 2011 3:31 AM writes...

Thank you so much. I have been looking for the top 200 drugs with their structures and inventors for a long time. Thanks.

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45. Yang Jia on December 2, 2011 10:07 AM writes...

It's very nice of you to post the top 200 drugs with their structures and inventors, which will help many people a lot to learn much about the development of pharmacy in our world.

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