See what was being read in January, February and March this year – free access:
Molecular obesity, potency and other addictions in drug discovery
Michael M. Hann
Med. Chem. Commun., 2011, 2, 349-355
Chemical space as a source for new drugs
Jean-Louis Reymond, Ruud van Deursen, Lorenz C. Blum and Lars Ruddigkeit
Med. Chem. Commun., 2010, 1, 30-38
Aromatic chloride to nitrile transformation: medicinal and synthetic chemistry
Lyn H. Jones, Nicholas W. Summerhill, Nigel A. Swain and James E. Mills
Med. Chem. Commun., 2010, 1, 309-318
Boronic acids in medicinal chemistry: anticancer, antibacterial and antiviral applications
Paul C. Trippier and Christopher McGuigan
Med. Chem. Commun., 2010, 1, 183-198
Small molecule modulation of stem cells in regenerative medicine: recent applications and future direction
Timothy E. Allsopp, Mark E. Bunnage and Paul V. Fish
Med. Chem. Commun., 2010, 1, 16-29
Silver nanoparticles—the real “silver bullet” in clinical medicine?
Kenneth K. Y. Wong and Xuelai Liu
Med. Chem. Commun., 2010, 1, 125-131
The importance of solvation in the design of ligands targeting membrane proteins
Angel González, Marta Murcia, Bellinda Benhamú, Mercedes Campillo, María L. López-Rodríguez and Leonardo Pardo
Med. Chem. Commun., 2011, 2, 160-164
The discovery of a novel prototype small molecule TLR7 agonist for the treatment of hepatitis C virus infection
David C. Pryde et al.
Med. Chem. Commun., 2011, 2, 185-189
Targeting epigenetic modifiers: Inhibitors of histone methyltransferases
Elisabeth-Maria Bissinger, Ralf Heinke, Wolfgang Sippl and Manfred Jung
Med. Chem. Commun., 2010, 1, 114-124
The p53-MDM2/MDMX axis – A chemotype perspective
Kareem Khoury, Grzegorz M. Popowicz, Tad A. Holak and Alexander Dömling
Med. Chem. Commun., 2011, 2, 246-260
The p53 signalling pathway is responsible for regulating the cell cycle, initiating DNA repair and triggering apoptosis where necessary. Its crucial importance can clearly be seen by the fact that about half of human cancers contain alterations in the p53 pathway. The proteins MDM2 and MDMX (a.k.a. MDM4) negatively regulate p53, and altered levels of these proteins are often deemed responsible for p53 alterations. As a result MDM2 has been extensively studied, but few MDM2 inhibitors have made it as far as clinical trials.
In this HOT paper David S. Millan and colleagues at Pfizer R&D explore the influence of intramolecular hydrogen bonding on the membrane permeability and bioavailability of some of these drugs. By determining the propensity of molecules to form intramolecular hydrogen bonds they are able to revise previous assumptions about where certain molecules sit in chemical space. They find that when hydrogen bonding is taken into account these drugs sit much closer to rule of five space – thereby explaining the successful absorption of drugs that otherwise violate rule of five principles.
The majority of therapeutics clinically available for cancer treatment are platinum-based and work via a DNA alkylation mechanism that leads to cell apoptosis. But a number of cancers are resistant to apoptosis and not treatable with platinum-based drugs.
