RSC Medicinal Chemistry Blog

Reviewing the pros and cons of protein structure-based pharmacophore modelling

20 Dec 2011

Pharmacophore modelling is a useful tool for medicinal chemists to identify novel ligands to bind to a receptor. This review from Chris de Graaf and colleagues describes the advantages, and challenges, of using 3D protein structures to predict pharmacophores (rather than using a ligand-based approach, which involves searching for similarities based on previously known active ligands).

The review covers (i) protein structure preparation, (ii) binding site detection, (iii) pharmacophore feature definition, and (iv) pharmacophore feature selection, concluding that ‘SBPs are valuable tools for hit and lead optimization, compound library design and target hopping, especially in cases where ligand information is scarce‘.

Epigenetics: a highly promising source of new drug targets

12 Dec 2011

By Marie Cote, Deputy Editor.

Strategies to unlock and read the epigenetic code for a new source of therapeutics

As an introduction to the web theme issue on Epigenetics published in MedChemComm (guest-edited by Dr Mark Bunnage – Pfizer – and Professor Rasmus Prætorius Clausen -University of Copenhagen), Nessa Carey (Head of Epigenetics ERDI, Pfizer) provides a concise summary of the current thinking in the ever expanding field of epigenetics.

Read Nessa’s review:
Epigenetics – an emerging and highly promising source of new drug targets
Nessa Carey
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00264C

…and view the collection of articles that makes for a timely and essential web theme issue in the emerging field of epigenetics research.

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Nominations for the 2012 RSC Prizes and Awards now open

05 Dec 2011

By Francesca Burgoyne.

Nominations for the 2012 RSC Prizes and Awards close on the 15 January 2012

Our Prizes and Awards represent the dedication and outstanding achievements and are a platform to showcase inspiring science to gain the recognition deserved. Don’t forget to nominate colleagues who have made a significant contribution to advancing the chemical sciences.

View our full list of Prizes and Awards and use the online system to nominate a colleague.

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Bio-polymer/silica composites for drug delivery and synthetic lung surfactants on the cover of Issue 12

30 Nov 2011

By Francesca Burgoyne.

Welcome to the final issue of 2011!

On the outside front cover of this issue is an article from Chang-Sik Ha and coworkers on a one step synthetic route to a hierarchical mesoporous bio-polymer/silica composite material with bimodal mesopores using a dual template of N,N,N-trimethyl chitosan (TMCs) and sodium dodecyl sulfate (SDS) for pH-sensitive targeted drug release.

Hierarchical mesoporous bio-polymer/silica composites co-templated by trimethyl chitosan and a surfactant for controlled drug delivery
Vijay Kumar Rana, Sung Soo Park, Surendran Parambadath, Mi Ju Kim, Sun-Hee Kim, Satyendra Mishra, Raj Pal Singh and Chang-Sik Ha
DOI: 10.1039/C0MD00222D

On the inside front cover Adrian Schwan et al. report a a novel phospholipase-resistant C16:0, C16:1 diether phosphonoglycerol as a synthetic lung surfactant with surface activity equivalent to calf lung surfactant extract.

Synthesis and activity of a novel diether phosphonoglycerol in phospholipase-resistant synthetic lipid:peptide lung surfactants
Adrian L. Schwan, Suneel P. Singh, Jason A. Davy, Alan J. Waring, Larry M. Gordon, Frans J. Walther, Zhengdong Wang and Robert H. Notter
DOI: 10.1039/C1MD00206F

As with all our cover articles these are free to access for 6 weeks.

View the rest of the issue here

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Drug-target residence times and covalent binders themed issue – call for papers

30 Nov 2011

By Francesca Burgoyne.

On behalf of Professor Dr Koen Augustyns (University of Antwerp), Guest Editor, we would like to invite authors to contribute to this themed issue which aims collect together in one place some of the latest exciting research from across the breadth of drug residence and covalent drug research.

Analysis of drug-target residence time has begun to play a larger role in drug discovery as suggested by recent literature. For compounds with a slow off rate, long action at the target may render a perfect pharmacokinetic profile unnecessary, and selectivity vs. other targets inhibited only briefly may be more readily achieved. Reversible and irreversible covalent binding drugs may be considered as the logical extreme for this approach. For other targets or therapeutic areas, other kinetic profiles may be desirable. Finally, there is a real need to build a better understanding in the medicinal chemistry community of the preferred profiles, screening methods, at which stage of a project lifetime to characterize the kinetics, and ideally a structural bases for design to achieve a desired kinetic profile.

-Koen Augustyns, Guest Editor

Authors will benefit from increased exposure of their research alongside similar high level and cutting edge work. In addition, as this is a web-based theme issue, printing of articles will not be held for a specific issue thereby allowing rapid dissemination of the science presented online and in print without delay. Both reviews and primary research are suitable for this issue.

The submission deadline for the web theme issue will be Monday 6^th February 2012.

If you would like to contribute to this exciting themed issue, please contact the Editorial Office.

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Make the most of the last month of free access from MedChemComm

29 Nov 2011

By Francesca Burgoyne.

Free online access to MedChemComm will finish at the end of 2011, but there is still time to take a look at all the articles we’ve published so far free of charge.

Don’t know where to start? Why not take a look at some of the top accessed articles over the last year:

Molecular obesity is weighing down drug discovery
Michael M. Hann, DOI: 10.1039/C1MD00017A

Michael Hann from GSK suggests that the search for potency can lead to drug molecules that are too large and liphophilic to make it to market, coining the term ‘molecular obesity‘ to describe the risk that this presents to the fitness of lead compounds.

Drugs that go beyond the rule of five – or do they?
Alexander Alex et al., DOI: 10.1039/C1MD00093D

David S. Millan and colleagues at Pfizer R&D explore the influence of intramolecular hydrogen bonding on the membrane permeability and bioavailability drugs which operate outside of the traditional rule of five – are they actually much closer to rule of five space than previously thought?

New antibiotics to repair faulty genes
Jeyakumar Kandasamy et al,. DOI: 10.1039/C0MD00195C

Timor Baasov and co-workers developed new aminoglycoside derivatives to suppress nonsense mutations, which result in a variety of genetic diseases, that show enhanced targeting and reduced cell toxicity compared to a leading antibiotic.

Novel indolizine compounds as potent inhibitors of phosphodiesterase IV (PDE4): structure–activity relationship
Shoujun Chen et al., DOI: 10.1039/C0MD00215A

2-Anilinonicotinyl linked 1,3,4-oxadiazole derivatives: Synthesis, antitumour activity and inhibition of tubulin polymerization
Ahmed Kamal et al., DOI: 10.1039/C0MD00177E

Impact of ion class and time on oral drug molecular properties
Paul D. Leeson, Stephen A. St-Gallay and Mark C. Wenlock, DOI: 10.1039/C0MD00157K

Structure–activity relationships of methyl-lysine reader antagonists
J. Martin Herold and Stephen V. Frye et al., DOI: 10.1039/C1MD00195G

New insight into the mode of action of vancomycin dimers in bacterial cell wall synthesis
Osamu Yoshida et al., DOI: 10.1039/C0MD00230E

If you would like to continue to receive access to MedChemComm in 2012 please contact sales@rsc.org and ask for a quote.

Additionally, why not consider submitting your next manuscript to the journal? We now also offer optional Accepted Manuscript publication, so that your manuscript is available faster in a citable form.

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Top ten most accessed articles in October

28 Nov 2011

By Nathalie Horner.

This month sees the following articles in MedChemComm that are in the top ten most accessed:

Towards biocompatible nanovalves based on mesoporous silica nanoparticles
Ying-Wei Yang
Med. Chem. Commun., 2011, 2, 1033-1049
DOI: 10.1039/C1MD00158B

Minisci reactions: Versatile CH-functionalizations for medicinal chemists
Matthew A. J. Duncton
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00134E

Are pyridazines privileged structures?
Camille G. Wermuth
Med. Chem. Commun., 2011, 2, 935-941
DOI: 10.1039/C1MD00074H

Molecular obesity, potency and other addictions in drug discovery
Michael M. Hann
Med. Chem. Commun., 2011, 2, 349-355
DOI: 10.1039/C1MD00017A

2-Anilinonicotinyl linked 1,3,4-oxadiazole derivatives: Synthesis, antitumour activity and inhibition of tubulin polymerization
Ahmed Kamal, Y. V. V. Srikanth, Thokhir B. Shaik, M. Naseer A. Khan, Md. Ashraf, M. Kashi Reddy, K. Anil Kumar and Shasi V. Kalivendi
Med. Chem. Commun., 2011, 2, 819-823
DOI: 10.1039/C0MD00177E

Potential atypical antipsychotics: synthesis, binding affinity and SAR of new heterocyclic bioisosteric butyrophenone analogues as multitarget ligands
María Barceló, Enrique Raviña, María J. Varela, José Brea, María I. Loza and Christian F. Masaguer
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00202C

Inhibitors of Stat5 protein signalling
Abbarna A. Cumaraswamy, Aleksandra Todic, Diana Resetca, Mark D. Minden and Patrick T. Gunning
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00175B

Structure–activity relationships of methyl-lysine reader antagonists
J. Martin Herold, Lindsey Ingerman James, Victoria K. Korboukh, Cen Gao, Kaitlyn E. Coil, Dennis J. Bua, Jacqueline L. Norris, Dmitri B. Kireev, Peter J. Brown, Jian Jin, William P. Janzen, Or Gozani and Stephen V. Frye
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00195G

Discovery of CP-866,087, a mu opioid receptor antagonist for the treatment of alcohol abuse and dependence
Stanton F. McHardy, Steven D. Heck, Sara Guediche, Monica Kalman, Martin P. Allen, Meihua Tu, Dianne K. Bryce, Anne W. Schmidt, Michelle Vanase-Frawley, Ernesto Callegari, Shawn Doran, Nicholas J. Grahame, Stafford McLean and Spiros Liras
Med. Chem. Commun., 2011, 2, 1001-1005
DOI: 10.1039/C1MD00164G

Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space
Alexander Alex, David S. Millan, Manuel Perez, Florian Wakenhut and Gavin A. Whitlock
Med. Chem. Commun., 2011, 2, 669-674
DOI: 10.1039/C1MD00093D

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to MedChemComm? Then why not submit to us today or alternatively email us your suggestions.

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Challenges in Organic Chemistry and Chemical Biology symposium

23 Nov 2011

By Francesca Burgoyne.

The first of the International Symposia on Advancing the Chemical Sciences (ISACS) series next year is to be Challenges in Organic Chemistry and Chemical Biology (ISACS7) on 12 – 15 June at the University of Edinburgh, UK.

See the excellent list of confirmed speakers and details of the abstract submission process here.

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HOT Review: Epigenetic modulators for cancer chemotherapy

21 Nov 2011

By Marie Cote, Deputy Editor.

In this Hot review article Professor Patrick Woster and a team of international collaborators provide insights into the design, synthesis and biological activity of a range of chromatin remodeling enzymes inhibitors that promote the re-expression of aberrantly silenced genes of importance in human cancer.

Interested in Epigenetic therapeutics? Why not read the article now:

Polyamine-based small molecule epigenetic modulators
DOI: 10.1039/C1MD00220A, Review

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Themed issue on Drug-Target Residence Times – deadline extended

15 Nov 2011

By Francesca Burgoyne.

We are pleased to inform our authors that we will be extending the submission deadline for our forthcoming drug-target residence times web theme issue to Monday 6^th February 2012.

The issue will be guest edited by Professor Dr Koen Augustyns (University of Antwerp) and aims collect together in one place some of the latest exciting research from across the breadth of drug residence research.

If you would like to contribute to this exciting themed issue, please contact the Editorial Office.

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RSC Medicinal Chemistry Blog

Reviewing the pros and cons of protein structure-based pharmacophore modelling

Epigenetics: a highly promising source of new drug targets

Nominations for the 2012 RSC Prizes and Awards now open

Bio-polymer/silica composites for drug delivery and synthetic lung surfactants on the cover of Issue 12

Drug-target residence times and covalent binders themed issue – call for papers

Make the most of the last month of free access from MedChemComm

Top ten most accessed articles in October

Challenges in Organic Chemistry and Chemical Biology symposium

HOT Review: Epigenetic modulators for cancer chemotherapy

Themed issue on Drug-Target Residence Times – deadline extended

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