Articles in 2012

Chris Lipinski, originator of the 'rule of five' guidelines for predicting the oral bioavailability of drug candidates, discusses their impact as well as efforts to expand drug-like chemical space and drug repositioning initiatives.

Tankyrases — members of the poly(ADP-ribose) polymerase (PARP) protein superfamily — are involved in diverse cellular processes, including WNT signalling and telomere maintenance. Here, the authors describe the biology of tankyrases and the discovery of tankyrase-specific inhibitors, which could have broad clinical utility. The challenges that lie ahead for the clinical development of PARP family inhibitors in general are also examined.

In vitropharmacological profiling is playing an increasing part in identifying undesirable off-target effects of candidate drugs earlier in the drug discovery process. In this article, authors from four large pharmaceutical companies share their views on the rationale, strategies and methodologies forin vitropharmacological profiling, and recommend a minimal panel of targets for screening.

Here, the authors discuss how cytokines could be used as therapeutic targets for individuals with asthma that is inadequately controlled using current therapies. They also highlight the need for phenotyping asthma subtypes in order to achieve the best possible patient-focused treatment.

The protein kinase C (PKC) family of highly related protein kinases are implicated in several diseases and have been a major focus of drug discovery efforts. However, no single drug specifically targeting a PKC isozyme has yet received approval. Here, Mochly-Rosen and colleagues review the efforts, challenges and opportunities in developing PKC modulators.

Long-standing efforts to develop drugs that target MEKs could soon come to fruition, moving the frontier to how best to combine them with other cancer therapies.

Garry Neil, acting CEO of TransCelerate, discusses the new precompetitive venture's aims to make clinical trials more efficient.

Less than a decade on from genetic studies indicating the potential of PCSK9 as a target to affect cholesterol metabolism, two PCSK9 inhibitors are moving into late-stage development.

Preclinical research indicates that various drugs approved for indications such as hypertension and diabetes could also have potentially beneficial effects in Alzheimer's disease, and for some drugs the evidence is also supported by epidemiological data or preliminary clinical trials. This article presents a formal consensus evaluation of these drug repositioning opportunities, and highlights several compounds for which sufficient evidence is available to encourage further investigation and potential progression to clinical trials in Alzheimer's disease.