Author Archive

Upcoming event: The Discovery of Abiraterone

6 pm, 20th September 2012
Chemistry Centre, Burlington House, London

The nature of drug discovery is changing, but the UK remains a world leader in the development of new medicines. The discovery of Abiraterone is one recent success, developed at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital (RMH). In 2011, it completed its journey from an idea to a life-extending treatment for men with advanced prostate cancer.

Keynote speaker: Professor Johann de Bono, Institute of Cancer Research  

Professor de Bono led on the drug’s development, taking it from Phase I first-in-man trials to the successful completion of Phase III trials. During his lecture he will highlight the Institute of Cancer Research’s unique partnership with the Royal Marsden hospital, with an emphasis on the bench-to-bedside approach that has already made a real impact on cancer patients’ lives. Professor de Bono’s talk will be followed by a chaired panel discussion which will address the question:

How can discovery programmes such as the successful work that led to the discovery of Abiraterone be repeated within the UK academic environment?

The evening will finish with a wine reception. This event is free to attend, but delegates must pre-register to guarantee admittance. Further details and online registration can be found at www.rsc.org/discovery-of-abiraterone

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The unusual case of a diterpenoid produced by Mycobacterium tuberculosis and its role in human infection

Reuben J. Peters  (Iowa State University) and Francis Mann (Winona Sate University) provide a short and topical account of the discovery of the isotuberculosinol diterpenoid prodution by bacteria Mycobacterium tuberculosis (Mtb).

The authors review the recent findings showing evidence of the biological role of this diterpenoid in the infection process of Mtb. Based on genetic and genomic analysis, the authors also provide insight into the origin of the tuberculosinol gene cluster and its role in human infection.

Curious? Why not read the review article now and let us know what you think…

Isotuberculosinol: the unusual case of an immunomodulatory diterpenoid from Mycobacterium tuberculosis
Francis M. Mann and Reuben J. Peters
DOI: 10.1039/C2MD20030A

This review is part of MedChemComm’s Natural Products themed issue, guest-edited by Prof. Christopher Walsh and Dr Sylvie Garneau-Tsodikova.

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Review: Natural products inhibitors of glucose-6-phosphate translocase

This mini-review authored by Prof. Chaitan Khosla and coworkers at Stanford University (CA, USA) provides a
concise overview of natural product inhibitors of the glucose-6-phosphate translocase (G6P T1) system.

Non-insulin dependant diabetes (type II) and carcinogenesis are two major diseases in which abberant glucose levels are observed, and for which glucose-6-phosphate translocase could be a promising therapeutic target.  Enzyme G6P T1 hydrolyses glucose-6-phosphate to glucose, which is then released into the bloodstream: modulating its activity may prove an attractive therapeutic strategy. 

Following an overview of the role of glucose-6-phosphate translocase in human physiology and its potential as a therapeutic target, the review covers its Natural Product inhibitors, including: 

  •    Chlorogenic acid and chlorogenic acid derivatives
  •    Phloretin
  •    Salicilic acid derived G6P T1 inhibitors
  •    Kodaistatins
  •    Mumbaistatins and Mumbaistatins derivatives 



Natural product inhibitors of glucose-6-phosphate translocase
Louise K. Charkoudian, Bailey P. Farrell and Chaitan Khosla
Med. Chem. Commun., 2012   
 






 Access the article by Chaitan Khosla et al. –  Access the full collection on Natural Products

 

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RSC US Roadshow 2012 – Week 4: North East

MedChemComm Editor Richard Kelly will be visiting several North East universities next week as part of the RSC US Roadshows 2012.

Week 4 sees the Royal Society of Chemistry visiting four universities in Pennsylvania and New York:

May 7th – University of Pittsburgh

May 8th – Pennsylvania State University

May 10th – University of Pennsylvania

May 11th – Columbia University

Read more about the US roadshows 2012:

Starting in mid April 2012, RSC Publishing has been touring the United States of America to share more than 170 years experience of publishing in the chemical sciences. Sixteen universities across the country are hosting these one-day events, which are open to all members of the hosting institute.

Attendees have the opportunity to explore RSC’s apps on mobile devices and meet informally with RSC editors. Lunchtime discussion groups explore reading habits and opportunities in the 21st century and an afternoon seminar give an insight into the world of scholarly publishing, with tips on how to get published in high impact journals. A demonstration of ChemSpider, and a guest lecture from an RSC associate editor or board member are available at many of the roadshows.

Follow the RSC Roadshows on Twitter – just look for #RSC2012.

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Review: Biosynthetic medicinal chemistry for lead advancement

‘Natural products are an unsurpassed source of lead structures for drug discovery. However, these molecules, many of which fall into the beyond-rule-of-5 chemical space, are often difficult to optimize by chemical means because of their complex structures.’, explains Frank E. Koehn (Pfizer, Natural Products, Oncology Worldwide Medicinal Chemistry Groton, USA).

In this MedChemComm review article, Frank E. Koehn provides the reader with an overview on biosynthesis-oriented strategies to access analogues of natural products, which would be unattainable by chemical semisynthesis. Five relevant examples of distinct drugs, namely:

  • salinosporamide
  • geldanamycin
  • FK506
  • rapamycin
  • epothilone

are described, for which libraries of analogues have been prepared via biosynthetic engineering approaches and which are under intensive biological investigation or already in clinical use.

This review is part of our forthcoming themed issue on Natural Products, guest edited by Professor Christopher T. Walsh and Dr Sylvie Garneau-Tsodikova – keep checking back for more hot research in this theme:

Biosynthetic medicinal chemistry of natural product drugs
Frank E. Koehn
Med. Chem. Commun., 2012, Review Article

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The Discovery of Brilinta – Daring to be Different

You are invited to attend the Royal Society of Chemistry’s Healthcare Innovation event on Wednesday 18 April, 5.30 pm at The Chemistry Centre, Burlington House, London, W1J 0BE

The Discovery of Brilinta – Daring to be Different
Dr John Dixon CChem FRSC

Over the last 30 years, improvements in healthcare and technology have led to an increase in life expectancy and a general rise in the level of health. The UK has for decades been a world leader in medicines discovery and research. The Discovery of Brilinta is a unique example of UK drug discovery excellence and is a potential blockbuster for the treatment of antithrombotic conditions for use in reducing heart attacks and cardiovascular death.
Our keynote speaker, Dr John Dixon will outline aspects of the discovery of Brilinta (ticagrelor) from the chemical starting point of ATP leading to a complex carbocyclic nucleoside analogue which was developed into a immediate release tablet. Ticagrelor is a reversible, selective P2Y12-receptor antagonist which was finally approved by the FDA in 2011 and is marketed in most countries.

The RSC has organised this event to highlight the pivotal role played by medicinal chemists in the discovery of Brilinta as well as provide a discussion forum for anyone who has an interest in the future of UK drug discovery. The nature of drug discovery is changing and is under considerable pressure due to escalating R&D costs and high drug discovery failure rates. Will it be possible to peruse complex drug discovery programmes in a fragmented environment?
I do hope you are able to join us for what will prove to be a very exciting and interesting lecture and discussion. Refreshments are available from 5.30 pm. The lecture will start at 6.00 pm and will be followed by a wine reception.

Please register here by 13 April or RSVP to sciencepolicy@rsc.org. Spaces are limited and will be allocated on a first come, first served basis.

About the Keynote speaker:
Dr John Dixon has 36 years experience of medicinal chemistry and drug discovery. He was Head of Medicinal Chemistry for 20 years at Fisons, Vice President of Pre Clinical R&D at Astra Charnwood for 4 years and Vice President of Drug Discovery at AstraZeneca Charnwood for 9 years. As VP of AstraZeneca Charnwood he was involved in development of 35 candidate drugs, particularly in the respiratory area. In July 2008, John became Director of JD International Consulting Ltd, an independent consultancy working with pharmaceutical and biotech organisations around the world. John is a Fellow of the Royal Society of Chemistry and Member of the American Chemical Society and has served on several professional and academic advisory committees.

Posted on behalf of the Conferences and Events team

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Review: Gd(III) chelates for MRI contrast agents

Kai-Hsiang Chuang and Chang-Tong Yang from the Singapore Bioimaging Consortium, A*STAR provide a timely review on the major developments of Gd(III) chelates as MRI contrast agents, from high relaxivity to ‘‘smart’’, from blood pool to blood–brain barrier.


The review covers:

  • Relaxivity of Gd(III) based MRI contrast agents
  • Smart contrast agents (pH-, metal ion-, enzyme- ; small biomolecule-activated)
  • Blood pool contrast agents (non-covalent binding to plasma proteins, polymeric and dendrimeric contrast agents)
  • Blood–brain barrier permeable contrast agents

Should your interests lie in coordination chemistry, polymer and supramolecular chemistry, medicinal chemistry, spectroscopy, biology or radiology, this review is for you!

Gd(III) chelates for MRI contrast agents: from high relaxivity to “smart”, from blood pool to blood–brain barrier permeable
Chang-Tong Yang and Kai-Hsiang Chuang
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00279E, Review Article

Why not also view our 2011 collection of topical review articles, across the full range of the journal scope, here.

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Review: Advances in design and drug discovery of antimalarial peroxides

In this MedChemComm review article Professor Gary H. Posner and coworkers at The Johns Hopkins Malaria Research Institute (Baltimore, MD, USA) provide an up-to-date review of the design and antimalarial activity of cyclic peroxides.

The review covers:

  • antimalarial monomeric and dimeric derivatives of artemisinin
  • peroxides not derived from artemisinin
  • hybrides containing one peroxide unit covalently linked to a non-peroxide unit.

… and highlights the effectiveness and the symplicity of synthesis of these diverse cyclic peroxides.

Reference
Antimalarial peroxides: advances in drug discovery and design
Rachel D. Slack, Alexander M. Jacobine and Gary H. Posner
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00277A, Review

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Chagas disease: selenosemicarbazones as new leads to beat drug resistant parasite

Scientists from Uruguay and the US have made new compounds that could be used to treat Chagas disease. Chagas disease is a parastic disease caused by the protozoan Trypanosoma cruzi. It affects an estimated 10 million people in South and Central America and results in 20 000 deaths each year.

The cysteine protease cruzipain is an essential T. cruzi enzyme and is one of the few validated drug targets for the disease. Current treatments include Nifurtimox and Benznidazole, but the cruzipain is becoming resistant to them.

Thiosemicarbazones have been described as cruzipain inhibitors. Now, the team have replaced the sulfur in these compounds with selenium to make selenosemicarbazones to find new drug leads. The selenosemicarbazones showed enhanced cysteine protease inhibitory activity compared to the thiosemicarbazones and to Benznidazole, one of the two current drugs on the market.

Selenosemicarbazones as Potent Cruzipain Inhibitors and their Antiparasitic Properties against Trypanosoma cruzi
Chiara Pizzo, Paula Faral-Tello, Gustavo Salinas, Martín Fló, Carlos Robello, Peter Wipf and Graciela Mahler
Med. Chem. Commun., 2011, Accepted Manuscript
DOI: 10.1039/C2MD00283C

Research on the Chagas and neglected diseases was also recently the subject of MedChemComm‘s latest poster prize.

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Meet the MedChemComm team

The MedChemComm team will be attending a number of conferences in 2012 and we would be delighted to meet you.

Dr Marie Cote, Deputy Editor

Dr Richard Kelly, Managing Editor

Here are just some of the conferences where you can meet us in the coming months:

Please let us know if you are planning on attending any of these meetings, as it would be lovely to meet you there!

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