Wavefunction Fieldofscience Com 2013 09 Macrocycle Drug Revi

pdfcrowd.comopen in browser PRO version Are you a developer? Try out the HTML to PDF API

FS AA AbC AL AS BF C6 CC CH CO/VL CW DM EP GEP GW HG IF LA MDB MPM PEM PX PY R6 RRR SW TPP VMGeology and Generals: HowGeology influenced the GettysburgCampaign (Part I.)1 hour ago in History of Geology

Rock Mosses12 hours ago inCatalogue ofOrganisms

Brazuca, aPogorelov's ball1 day ago in DocMadhattan

Vertebrate sexualsystems1 day ago inPleiotropy

Garden gnome drone1 day ago in The Phytophactor

Musings on drug discovery, chemistry and the endless frontier of science.

The Curious Wavefunction

By Wavefunction on Tuesday, September 03, 2013

Macrocycle drug reviewRecommend this on Google

Here's a comprehensive and useful review of macrocycle drugs in J Med Chem by Giordanetto andKihlberg at AstraZeneca; well worth reading to get an idea of what's out there in the clinic and on themarket.

The authors looked at about 30 clinical macrocycle candidates and 70 marketed macrocycle drugs andanalyzed their principal physicochemical properties to investigate trends and differences. Some mainpoints emerging from the discussion:

1. Most macrocycles are in oncology or infection; however, the ones that are targeted toward otherareas include a significant number of de-novo synthetic or semisynthetic molecules from structure-based drug design.2. Among marketed macrocycles, injected drugs are mostly cyclic peptides while oral drugs are mostlymacrolides (in general, injectable macrocycles seem to span a broader chemical space).3. The structural differences between oral and injectable macrocycles can often be pretty trivial (atleast on inspection; eg. tacrolimus vs pimecrolimus).4. For oral macrocycles, increasing MW seems to track with increasing lipophilicity.5. There's a set of plots which indicates the limits of chemical space within which marketedmacrocycles seem to lie. "Rogue" rule-breakers like cyclosporin which lie very far from this space arestill exceptions.

The question of whether we can deliberately engineer drug molecules to act like cyclosporin on a largescale is still very much an open one. What is clear is that we are increasingly making molecules thatare decidedly testing the boundaries of the rule-of-5 and pushing the envelope. The future is not

Ashutosh (Ash) Jogalekar is a scientist working in biotechnology anddrug discovery in Cambridge, MA. He is interested in the history andphilosophy of science. Ash also blogs at The Curious Wavefunction onScientific American Blogs and can be reached at curiouswavefunction"at" gmail "dot" com.

About Me

Search

Subscribe

Posts

Comments

Molecular modeling andphysics: A tale of twodisciplinesThe LHC is a product of bothtime and multipledisciplinesIn my professionalfield of molecular modelingand drug discovery I often feel

Previous Posts

Join this sitew ith Google Friend Connect

Members (124) More »

Already a member? Sign in

Follow

Blogroll

http://feedproxy.google.com/~r/curiouswavefunction/~3/cJV2O7wmhdA/molecular-modeling-and-physics-tale-of.html

http://blogs.scientificamerican.com/the-curious-wavefunction/

http://pubs.acs.org/doi/abs/10.1021/jm400887j

http://www.blogger.com/share-post.g?blogID=9633767&postID=6423960162993978807&target=pinterest

http://www.blogger.com/share-post.g?blogID=9633767&postID=6423960162993978807&target=facebook

http://www.blogger.com/share-post.g?blogID=9633767&postID=6423960162993978807&target=twitter

http://www.blogger.com/share-post.g?blogID=9633767&postID=6423960162993978807&target=blog

http://www.blogger.com/share-post.g?blogID=9633767&postID=6423960162993978807&target=email

http://wavefunction.fieldofscience.com/2013/09/macrocycle-drug-review.html

http://wavefunction.fieldofscience.com/

http://feedproxy.google.com/~r/Phytophactor/~3/HfKtrIkICdc/garden-gnome-drone.html

http://feedproxy.google.com/~r/PleiotropyFeed/~3/mdaZ8Ne54t0/vertebrate-sexual-systems.html

http://feedproxy.google.com/~r/PleiotropyFeed/~3/mdaZ8Ne54t0/vertebrate-sexual-systems.html

http://feedproxy.google.com/~r/DocMadhattan/~3/NgUN4CFVLG8/brazuca-pogorelovs-ball.html

http://feedproxy.google.com/~r/DocMadhattan/~3/NgUN4CFVLG8/brazuca-pogorelovs-ball.html

http://coo.fieldofscience.com/2014/06/rock-mosses.html

http://coo.fieldofscience.com/2014/06/rock-mosses.html

http://feedproxy.google.com/~r/History-of-Geology/~3/xWnmO8vxItc/geology-and-generals-how-geology.html

http://theviewfromamicrobiologist.fieldofscience.com/

http://phytophactor.fieldofscience.com/

http://skepticwonder.fieldofscience.com/

http://rrresearch.fieldofscience.com/

http://ruleof6ix.fieldofscience.com/

http://pleiotropy.fieldofscience.com/

http://plektix.fieldofscience.com/

http://proteinevolution.fieldofscience.com/

http://mossplants.fieldofscience.com/

http://defectivebrain.fieldofscience.com/

http://labs.fieldofscience.com/

http://inkfish.fieldofscience.com/

http://historyofgeology.fieldofscience.com/

http://gameswithwords.fieldofscience.com/

http://genome.fieldofscience.com/

http://epiphenom.fieldofscience.com/

http://docmadhattan.fieldofscience.com/


http://taxondiversity.fieldofscience.com/

http://coo.fieldofscience.com/

http://chinleana.fieldofscience.com/

http://cultureofchemistry.fieldofscience.com/

http://ecophysio.fieldofscience.com/

http://biologyfiles.fieldofscience.com/

http://theastronomist.fieldofscience.com/

http://allotrope.fieldofscience.com/

http://angrybychoice.fieldofscience.com/

http://a-is-for-aspirin.fieldofscience.com/

http://www.fieldofscience.com/


http://pdfcrowd.com/html-to-pdf-api/?ref=pdf

http://pdfcrowd.com/customize/

http://pdfcrowd.com/redirect/?url=http%3a%2f%2fwavefunction.fieldofscience.com%2f2013%2f09%2fmacrocycle-drug-review.html&id=ma-140630134531-be4d4baf

http://pdfcrowd.com


Newer Post Older PostHome

Subscribe to: Post Comments (Atom)

Labels: macrocycles

guaranteed, but it's promising.

Markup Key:- <b>bold</b> = bold- <i>italic</i> = italic- <a href="http://www.fieldofscience.com/">FoS</a> = FoS

Enter your comment...

Comment as: Select profile...

Publish

Preview

Create a Link

No comments:

Post a Comment

Links to this post

and drug discovery I often feellike an explorer who hasarrived on the shores of a newcontinent with a very sketc...Crystallography andchemistry: The culture issueImage: Charles Reynolds andACS Med Chem LettersAs theold saying goes, beware ofcrystallographers bearingligands. Charles Reynoldswho is a well-knownstructure-based drug designexpert has an editorial in ACSMedicin...Phil Baran is a man of style.We, of course, knew that for awhile.Thanks to @ChemicalBiologyI just came to know about apiece of news that maysimultaneously help resurrectchemistry's moribund publicimage and disintegratemultiple damsel heartsas efficiently as heterolyticbon...Free Energy Perturbation(FEP) methods in drugdiscovery: Or, Waiting forGodotFor interested folks in theBoston area it's worth taking alook at this workshop on FreeEnergy Perturbation (FEP)methods in drug design atVertex from May 19-21. Thelist of speakers and topics isquite impressive, an...The structure of DNA, 61years later: How they did it."A Structure for DeoxyriboseNucleic Acid", Nature, April 25,1953 (Image: Oregon StateUniversity)This month marksthe sixty-first anniversary ofthe publication of thelandmark paper on thestructure of DNA by Watson ...

(no title)ANALOGIES BETWEEN

Popular Posts

Dylan's TenderblogRetreadIn The PipelineCarbon-based CuriositiesChembarkJust Like CookingBiochem BelleSciencegeistMaster Organic ChemistryCulture of ChemistryBosco HoHenry RzepaThe Stoichiometric EquivalentSecond MessengerC & EN blogBunsen BoernerChemjobberChemical CrystallinityIn Vivo BlogSoft MachinesA Life in the Biophysics LabKinaseProComp Org ChemInterfacial DigressionsEveryday ScientistLamentations on ChemistryDiscount ThoughtsTotally SyntheticAndrewHomebrew & ChemWater In BiologyCurly ArrowChemical blogspaceChemistry BlogGMCrapshootMaking Graphite WorkOrg Prep DailySkeptical ChymistQuantum PontiffChemical Quantum Images

0 0 0Reddit 109

http://chemical-quantum-images.blogspot.com/

http://scienceblogs.com/pontiff/

http://blogs.nature.com/thescepticalchymist/

http://orgprepdaily.wordpress.com/

http://http://graphiteworks.wordpress.com/

http://gmc2007.blogspot.com/

http://www.chemistry-blog.com/

http://cb.openmolecules.net/

http://curlyarrow.blogspot.com/

http://waterinbiology.blogspot.com/

http://homebrewandchemistry.blogspot.com/

http://network.nature.com/blogs/user/andrewsun

http://www.totallysynthetic.com/blog/

http://mwclarkson.blogspot.com/

http://gaussling.wordpress.com/

http://blog.everydayscientist.com/

http://interfacialdigressions.blogspot.com/

http://hackberry.chem.trinity.edu/blog/

http://kinasepro.wordpress.com/

http://larsduelund.wordpress.com/

http://www.softmachines.org/wordpress/

http://invivoblog.blogspot.com/

http://chemicalcrystallinity.blogspot.com/

http://chemjobber.blogspot.com/

http://ljkboerner.wordpress.com/

http://cenblog.org/

http://chemicalphysiology.blogspot.com/

http://stoichiometricequiv.blogspot.com/

http://www.ch.imperial.ac.uk/rzepa/blog/

http://boscoh.com/

http://cultureofchemistry.blogspot.com/

http://masterorganicchemistry.com/

http://sciencegeist.net/

http://biochembelle.wordpress.com/

http://justlikecooking.blogspot.com/

http://blog.chembark.com/

http://www.coronene.com/blog

http://pipeline.corante.com/

http://luysii.wordpress.com/

http://blog.tenderbutton.com/

http://wavefunction.fieldofscience.com/2007/04/analogies-between-analogies-dereks-post.html

http://feedproxy.google.com/~r/curiouswavefunction/~3/aUCeklqEwN4/the-structure-of-dna-61-years-later-how.html

http://feedproxy.google.com/~r/curiouswavefunction/~3/JrnGr9RL_Oo/free-energy-perturbation-fep-methods-in.html

http://feedproxy.google.com/~r/curiouswavefunction/~3/37U9joVRKxA/phil-baran-is-man-of-style-we-of-course.html

http://feedproxy.google.com/~r/curiouswavefunction/~3/ibFxFkNMp5A/crystallography-and-chemistry-culture.html

http://www.blogger.com/blog-this.g


http://wavefunction.fieldofscience.com/search/label/macrocycles

http://wavefunction.fieldofscience.com/feeds/6423960162993978807/comments/default


http://wavefunction.fieldofscience.com/2013/08/so-you-hate-gmos-because-they-are.html

http://wavefunction.fieldofscience.com/2013/09/chemical-and-engineering-news_10.html




http://pdfcrowd.com


ANALOGIES Derek's postabout metaphors andanalogies reminded me of aquote by a remarkablemathematician whose na...

A discussion on Big Science,Small Science and the futureof all scienceTomorrow I have the privilegeof joining a panel discussion on Big Science with three verydistinguished scientists:Nobel Laureate Ste...

Crystallography andchemistry: The culture issueImage: Charles Reynolds andACS Med Chem Letters As theold saying goes, beware ofcrystallographers bearingligands. Charles Reynolds ...

The difference betweenchemistry and physicsI came across the followingquote by the Nobel Prizewinning chemist WilliamLipscomb (think diborane,carbonic anhydrase) withwhich I gene...

Molecular dynamics: I have abad feeling about this.Computer models ofchemical and biologicalsystems are not reality; ratherthey are what I call “invitationsto reality”. They ...

Molecular modeling andphysics: A tale of twodisciplinesThe LHC is a product of bothtime and multiple disciplinesIn my professional field ofmolecular modeling and drugdiscovery I often fe...

Vytorin: New Problems for aNew Era

Chemical Quantum Images

NatureScienceJACSAngewandte ChemieJ. Med. Chem.Organic LettersJ. Org. Chem.ChemCommChemBioChemChem. & Biol.Chem. Eur. Jour.ChemMedChemStructureJ. Comp. Chem.J. Phys. Chem. AJ. Phys. Chem. BBiophys. J.BiochemistryJ. Biol. ChemJ. Mol. Bio.Nat. Chem. Biol.ACS Chem. Biol.ProteinsCellBr. J. Pharmacol.Mol. Pharm.JAMALancetNEJMCancer Res.J. Neurochem.Bioorg. Med. Chem. Lett.PNASPLOS

Journals and Magazines

Archives

http://www.plos.org/

http://www.pnas.org/

http://www.sciencedirect.com/science?_ob=PublicationURL&_cdi=5221&_pubType=J&_auth=y&_acct=C000034138&_version=1&_urlVersion=0&_userid=655046&md5=a71b01407754102b8df0c76e4197c17d

http://www.blackwell-synergy.com/loi/jnc

http://cancerres.aacrjournals.org/current.shtml

http://content.nejm.org/current.shtml

http://www.thelancet.com/

http://jama.ama-assn.org/

http://molpharm.aspetjournals.org/current.shtml

http://www.nature.com/bjp/index.html

http://www.cell.com/

http://www3.interscience.wiley.com/cgi-bin/jhome/36176

http://pubs.acs.org/journals/acbcct/index.html

http://www.nature.com/nchembio/index.html

http://www.sciencedirect.com/science/journal/00222836

http://www.jbc.org/current.shtml

http://pubs.acs.org/journals/bichaw/index.html

http://www.biophysj.org/current.shtml

http://pubs.acs.org/journals/jpcbfk/

http://pubs.acs.org/journals/jpcafh/index.html


http://www.structure.org/


http://www3.interscience.wiley.com/cgi-bin/jhome/26293/

http://www.chembiol.com/


http://www.rsc.org/publishing/journals/CC/article.asp?type=CurrentIssue

http://pubs.acs.org/journals/joceah/index.html

http://pubs.acs.org/journals/orlef7/index.html

http://pubs.acs.org/journals/jmcmar/index.html

http://www.wiley-vch.de/publish/en/journals/alphabeticIndex/2002/?jURL=http://www.wiley-vch.de/vch/journals/2002/cover/current.html

http://pubs.acs.org/journals/jacsat/index.html

http://www.sciencemag.org/

http://www.nature.com/index.html

http://chemical-quantum-images.blogspot.com/

http://wavefunction.fieldofscience.com/2008/09/vytorin-new-problems-for-new-era.html

http://wavefunction.fieldofscience.com/2014/06/molecular-modeling-and-physics-tale-of.html

http://wavefunction.fieldofscience.com/2013/10/molecular-dynamics-i-have-bad-feeling.html

http://wavefunction.fieldofscience.com/2010/09/difference-between-chemistry-and.html

http://wavefunction.fieldofscience.com/2014/06/crystallography-and-chemistry-culture.html

http://wavefunction.fieldofscience.com/2013/10/a-discussion-on-big-science-small.html

http://wavefunction.fieldofscience.com/2014/06/crystallography-and-chemistry-culture.html




http://pdfcrowd.com


The NYT has a piece today inwhich it describes theproblems riddling Vytorin , acombination of ezetimibe andsimvastatin , which is take...

Molecularmodeling: Howfar can physicstake us?Of all thescientists

writing about modeling andsimulation in drug discoveryin the last decade or so, Ihave found Anthony Nichollsof Op...

Why biology(andchemistry) isnot physicsI n the WallStreet Journal,

the physics writer JeremyBernstein has a fine review ofa new joint biography by GinoSegre of George Gamow a...

2013 Nobel PrizesIt's almost time for the 2013Nobel Prizes, which meansit's also time for playing thatlittle game which we in thechemosphere hav...

► 2014 (24)

▼ 2013 (51)► December (2)

► November (3)

► October (6)

▼ September (5)Phil Baran keeps the

dream of classicalorganic ch...

2013 Nobel Prizes

MIT and chemistry: Whatgives?

Chemical and EngineeringNews celebrates 90years:...

Macrocycle drug review

► August (7)

► July (3)

► May (6)

► April (3)

► March (4)

► February (6)

► January (6)

► 2012 (79)

► 2011 (82)

► 2010 (95)

► 2009 (112)

► 2008 (77)

► 2007 (133)

► 2006 (59)

► 2005 (19)

► 2004 (3)

http://extremetracking.com/open?login=ajogale

http://wavefunction.fieldofscience.com/search?updated-min=2004-01-01T00:00:00-08:00&updated-max=2005-01-01T00:00:00-08:00&max-results=3









http://wavefunction.fieldofscience.com/2013_01_01_archive.html







http://wavefunction.fieldofscience.com/2013/09/macrocycle-drug-review.html

http://wavefunction.fieldofscience.com/2013/09/chemical-and-engineering-news_10.html

http://wavefunction.fieldofscience.com/2013/09/mit-and-chemistry-what-gives.html

http://wavefunction.fieldofscience.com/2013/09/2013-nobel-prizes.html

http://wavefunction.fieldofscience.com/2013/09/phil-baran-keeps-dream-of-classical.html







http://wavefunction.fieldofscience.com/2013/09/2013-nobel-prizes.html

http://wavefunction.fieldofscience.com/2011/08/why-biology-and-chemistry-is-not.html

http://wavefunction.fieldofscience.com/2012/01/molecular-modeling-how-much-can-physics.html

http://wavefunction.fieldofscience.com/2011/08/why-biology-and-chemistry-is-not.html

http://wavefunction.fieldofscience.com/2012/01/molecular-modeling-how-much-can-physics.html




http://pdfcrowd.com


Field of ScienceBlogs:

A is for AspirinAngry by ChoiceC6-H12-O6Catalogue of OrganismsChinleanaDoc MadhattanEpiphenomGames w ith WordsGenomics, Evolution, and PseudoscienceHistory of GeologyInkfishLabsMemoirs of a Defective BrainMoss Plants and MorePleiotropyPlektixProtein Evolution and Other MusingsRRResearchRule of 6ixSkeptic WonderThe AllotropeThe AstronomistThe Biology FilesThe Culture of ChemistryThe Curious WavefunctionThe PhytophactorThe View from a MicrobiologistVariety of Life

Field of Science

about | contact | archives & alumni subscribe: feed - email follow : tw itter - facebook - badge

Latest From The Network...

Powered by Y! Pipes™

http://pipes.yahoo.com/

http://pipes.yahoo.com/

http://pipes.yahoo.com/pipes/badge.config?page=1&_btype=list&_id=PoOyY8v63RGxv8s3bbsjiw

http://www.facebook.com/fieldofscience

http://www.twitter.com/fieldofscience

http://feedburner.google.com/fb/a/mailverify?uri=FoSCombinedFeed

http://feeds.feedburner.com/FoSCombinedFeed

http://www.fieldofscience.com/p/archives-alumni.html

http://www.fieldofscience.com/p/contact.html

http://www.fieldofscience.com/p/about.html


http://taxondiversity.fieldofscience.com/

http://theviewfromamicrobiologist.fieldofscience.com/

http://phytophactor.fieldofscience.com/


http://cultureofchemistry.fieldofscience.com/

http://biologyfiles.fieldofscience.com/

http://theastronomist.fieldofscience.com/

http://allotrope.fieldofscience.com/

http://skepticwonder.fieldofscience.com/

http://ruleof6ix.fieldofscience.com/

http://rrresearch.fieldofscience.com/

http://proteinevolution.fieldofscience.com/

http://plektix.fieldofscience.com/

http://pleiotropy.fieldofscience.com/

http://mossplants.fieldofscience.com/

http://defectivebrain.fieldofscience.com/

http://labs.fieldofscience.com/

http://inkfish.fieldofscience.com/

http://historyofgeology.fieldofscience.com/

http://genome.fieldofscience.com/

http://gameswithwords.fieldofscience.com/

http://epiphenom.fieldofscience.com/

http://docmadhattan.fieldofscience.com/

http://chinleana.fieldofscience.com/

http://coo.fieldofscience.com/

http://ecophysio.fieldofscience.com/

http://angrybychoice.fieldofscience.com/

http://a-is-for-aspirin.fieldofscience.com/





http://pdfcrowd.com

Wavefunction Fieldofscience Com 2013 09 Macrocycle Drug Revi

Documents

Transcript of Wavefunction Fieldofscience Com 2013 09 Macrocycle Drug Revi