RSC Medicinal Chemistry Blog

Small molecules targeting phosphoinositide 3-kinases

01 Aug 2012

The phosphoinositide 3-kinase (PI3K) pathway is one of the most important signalling cascades in cancer. It has been well established as an attractive oncology target and inhibitors of PI3K have been suggested as promising agents for therapeutic intervention in cancer. Since the discovery of wortmannin and LY294002, the first compounds to inhibit PI3K, a vast number of inhibitors have been identified.

This review from Peng Wu and Yongzhou Hu, Zhejiang University, outlines the current landscape of the development of small molecule PI3K inhibitors, with a focus on structure–activity relationships (SAR) and discussion of co-crystal structures of the twenty-two molecules that are currently under clinical trials and newly emerged ones.

Read the review and let us know your thoughts by commenting below on this blog!

Small molecules targeting phosphoinositide 3-kinases
Peng Wu and Yongzhou Hu
DOI: 10.1039/C2MD20044A

Comments Off on Small molecules targeting phosphoinositide 3-kinases

MedChemComm’s Natural Products themed issue now published online

30 Jul 2012

By James Anson.

Issue 8 of MedChemComm has arrived and it’s a Natural Products themed issue that is filled to bursting with: nine reviews elegantly summarising the synthesis, biosynthesis, inhibitory properties and targets, and biological functions of natural products, as well as new bioinformatics methods for their identification; and fourteen concise articles describing some of the newest discoveries in the field of natural products.

An example of such a concise article is featured on the inside cover of the issue:

Synthesis and anti-Helicobacter pylori activity of analogues of spirolaxine methyl ether
Ivaylo Dimitrov, Daniel P. Furkert, John D. Fraser, Fiona J. Radcliff, Orla Finch and Margaret A. Brimble
DOI: 10.1039/C2MD00314G

To check out the entire themed issue now click here…

A big thank you must go to the guest editors Professor Christopher Walsh (Harvard University) & Dr Sylvie Garneau-Tsodikova (University of Michigan) for all their hard work, and to all those who have contributed to this issue for making this issue such a success.

Finally, below is a cover suggestion from Amanda J. Hughes et al., which we really liked but which we were unfortunately unable to use on the cover, so we thought we would share it with you here.

Employing a polyketide synthase module and thioesterase in the semipreparative biocatalysis of diverse triketide pyrones
Amanda J. Hughes, Joshua F. Detelich and Adrian T. Keatinge-Clay
DOI: 10.1039/C2MD20013A

Comments Off on MedChemComm’s Natural Products themed issue now published online

Congratulations to Dr Patrick Gunning, recipient of the inaugural MedChemComm Emerging Investigator Lectureship

25 Jul 2012

By Richard Kelly.

We are delighted to announce that Dr Patrick Gunning from the University of Toronto (Canada) is the recipient of the inaugural MedChemComm Emerging Investigator Lectureship.

The MedChemComm mission is to publish and promote research which pushes the boundaries of what is thought possible in medicinal chemistry, opening up new avenues of research. The committee felt Dr Gunning to be an outstanding candidate for the Lectureship, with his prominent work into the investigation and manipulation of protein function exemplifying the journal’s mission.

On receiving the Lectureship Dr Gunning said “I am absolutely delighted and honoured to be the recipient of the 2012 RSC MedChemComm Lectureship. It is a wonderful surprise!” Commenting on Dr Gunning’s Lectureship, Professor Andrew Hamilton, Vice Chancellor of Oxford University, said “Over the past several years Patrick has made an outstanding start to his independent research career. His work on disruptors of STAT3 function is both innovative and effective, and has the potential to open a new line of attack on some of the most aggressive cancers. I have also enjoyed reading his exciting and novel approach to targeting cancer through redirecting various oncoproteins from their targets to harmless anchoring into the cell membrane.”

Dr Gunning will deliver the Lecture at an international conference in the next year. This will be announced in due course.

The MedChemComm Emerging Investigator Lectureship is an annual Lectureship which is given to a researcher who has made a significant contribution to medicinal chemistry research in the early part of their career. The recipient must also have published an article in MedChemComm. Nominations are received from members of the public and the recipient is chosen by a committee formed of members of the Editorial Board. Nominations for the 2013 Lectureship will open in late 2012.

View Dr Gunning’s recent articles:

Src homology 2 domain proteomimetics: developing phosphopeptide selective receptors
Joel A. Drewry, Steven Burger, Amir Mazouchi, Eugenia Duodu, Paul Ayers, Claudiu C. Gradinaru and Patrick T. Gunning
Med. Chem. Commun., 2012, 3, 763-770

Inhibitors of Stat5 protein signalling
Abbarna A. Cumaraswamy, Aleksandra Todic, Diana Resetca, Mark D. Minden and Patrick T. Gunning
Med. Chem. Commun., 2012, 3, 22-27

Comments Off on Congratulations to Dr Patrick Gunning, recipient of the inaugural MedChemComm Emerging Investigator Lectureship

Delivering insulin in a skin cream

24 Jul 2012

By James Anson.

Insulin could be administered topically rather than by needles in the future

Scientists in Japan have developed a way to administer insulin to patients through the skin. Such a method avoids one of the problems associated with injections and oral administration in which a drug’s concentration is reduced as it passes through the digestive system. It would also be a more pleasant experience for patients.

Masahiro Goto from Kyushu University in Fukuoka and SO Pharmaceutical Corporation in Kobe, and colleagues, prepared a capsule loaded with insulin that is able to penetrate the skin with its cargo.

The team made their capsule by surrounding insulin molecules with proteins and coating the protein molecules with a hydrophobic surfactant to form protein–surfactant complexes. Then, they added oligo-arginine peptides as protein transduction domains and dispersed the complexes in oil – isopropyl myristate – which is known to have a permeation-enhancing effect. ‘The main function of this new system is to promote protein penetration through the hydrophobic stratum corneum [outermost layer of the skin],’ explains Goto.

The team tested their delivery vehicle on pig skin and found that the solid-in-oil dispersion delivered six times more insulin into the skin than an aqueous solution. The peptides further enhanced the concentration of insulin delivered through the skin.

‘Transcutaneous protein delivery is a difficult problem, the solution of which could enhance the quality of life for patients in need of protein therapeutics,’ says Paschalis Alexandridis from the chemical and biological engineering department at the University of Buffalo, US, whose work includes pharmaceutical formulations. He adds that Goto’s work demonstrates the versatility of solid-in-oil nanodispersions as a platform for enhanced transdermal delivery of protein therapeutics and vaccines.

Goto and his team say that in theory such dispersion could be used for any drug that is soluble in water and can form a water-in-oil emulsion. They hope to be able to produce a transdermal vaccine in the future.

Original story from Chemistry World, written by Jennifer Newton

Comments Off on Delivering insulin in a skin cream

Natural product-like cyclic peptide libraries by biochemical & biosynthetic preparation

16 Jul 2012

By James Anson.

Albert A. Bowers, Purdue University, provides a review focussing on emerging biochemical and biosynthetic methods for the development of peptidomimetic libraries, in particular constrained cyclic peptide libraries that contain natural product-like features, with an emphasis given to small molecules of 30 residues or less.

Discussion includes:

Non-ribosomal peptide synthetases (NRPS) or hybrid polyketide (NRPS/PKS) derived libraries
Ribosomal peptide libraries
Non-natural product-based technologies for library preparation

Want to know more? Have a look now and let us know your thoughts…

Biochemical and biosynthetic preparation of natural product-like cyclic peptide libraries
Albert A. Bowers
DOI: 10.1039/C2MD20068F

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

Comments Off on Natural product-like cyclic peptide libraries by biochemical & biosynthetic preparation

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

06 Jul 2012

By Marie Cote, Deputy Editor.

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.

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

Submit a poster for Lipids and Membrane Biophysics: Faraday Discussion 161

04 Jul 2012

By James Anson.

There’s still just time to submit a poster for Lipids and Membrane Biophysics: Faraday Discussion 161 – by the deadline date 13 July.

This Faraday Discussion will consider recent developments in the study of biomembrane structure, ordering and dynamics, with particular emphasis on the roles of lipids in these phenomena. Registration is quick and simple via our online booking system, so act today and benefit from early bird savings.

Why choose to come to a Faraday Discussion? They have a unique format – all papers are circulated in advance and all discussion contributions are recorded for publication in the abstract book after the event. You can also have your own poster space at the meeting, so submit yours now before the deadline of 13 July.

Come and discuss new experimental and theoretical findings and novel methodologies, as we focus on exploring the relevance of concepts from amphiphile self-assembly and soft matter physics to understanding biomembranes.

Comments Off on Submit a poster for Lipids and Membrane Biophysics: Faraday Discussion 161

2011 Impact Factor for OBC, MedChemComm & NPR

29 Jun 2012

By James Anson.

The 2011 Journal Citation Reports ® (Thomson Reuters, 2012) have just been released, which showed:

Organic & Biomolecular Chemistry: 3.696

MedChemComm: 2.8 (Partial IF only, based on five issues)

Natural Product Reports: 9.79

The Cambridge Editorial Office would like to thank everyone involved for their hard work and dedication to all three journals over the years. In particular, we would like to thank all of our Associate Editors, Editorial and Advisory Board members, authors and referees, without whom none of this would have been possible.

With another successful year in the bag, we hope you will join us in making this year even better…

Read more about the 2011 Impact Factors from across RSC Publishing on the RSC Publishing Blog.

Comments Off on 2011 Impact Factor for OBC, MedChemComm & NPR

RSC Medicinal Chemistry Blog

Small molecules targeting phosphoinositide 3-kinases

MedChemComm’s Natural Products themed issue now published online

Congratulations to Dr Patrick Gunning, recipient of the inaugural MedChemComm Emerging Investigator Lectureship

Top ten most accessed articles in June

Delivering insulin in a skin cream

Natural product-like cyclic peptide libraries by biochemical & biosynthetic preparation

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

Submit a poster for Lipids and Membrane Biophysics: Faraday Discussion 161

Top ten most accessed articles in May

2011 Impact Factor for OBC, MedChemComm & NPR

Links

Categories

Archives

Meta