Chemistry & Biology

27 January, 2012
Volume 19, Issue 1

Volume 19, Issue 1

On the cover: The current reality of modern drug discovery and development is that the process of bringing a new drug to the market is increasingly painstaking, with efforts to develop new medicines often taking more than a decade. This is compounded by the increasing need for new therapeutics either to address new clinical indications or to readdress the number of conditions battling with a surge in resistance to available drugs. This special issue of Chemistry & Biology provides a look at drug discovery and development from diverse chemical biology perspectives. Included contributions highlight numerous innovative approaches poised to tackle the challenges.

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Reviews in Chemistry & Biology

Generation, Translocation, and Action of Nitric Oxide in Living Systems

Andrew G. Tennyson, Stephen J. Lippard

Traffic Jam at the Bacterial Sec Translocase: Targeting the SecA Nanomotor by Small-Molecule Inhibitors

Kenneth Segers, Jozef Anné

Regenerative Chemical Biology: Current Challenges and Future Potential

Ada Ao, Jijun Hao, Charles C. Hong

Lipidomics at the Interface of Structure and Function in Systems Biology

Richard W. Gross and Xianlin Han

Confronting the Challenges of Natural Product-Based Antifungal Discovery

Terry Roemer, Deming Xu, Sheo B. Singh, Craig A. Parish, Guy Harris, Hao Wang, Julian E. Davies, Gerald F. Bills

Biocompatible Quantum Dots for Biological Applications

Sandra J. Rosenthal, Jerry C. Chang, Oleg Kovtun, James R. McBride, Ian D. Tomlinson

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Special Reviews Issue

Volume 19 Issue 1: January 26, 2012

Next issue: February 23, 2012

Drug Discovery and Development

Current reality of modern drug discovery and development is that the process of bringing a new drug to the market is increasingly painstaking and time consuming, with efforts to develop new medicines taking more than a decade. This is compounded by the increasing need for new therapeutics to address either new clinical needs or to readdress number of conditions battling with surge in resistance to available drugs. The Special Issue of Chemistry & Biology provides a look at drug discovery and development from diverse chemical biology perspectives, poised to tackle these challenges by numerous innovative approaches highlighted in included contributions. The access to all perspective and review articles in this issue is FREE!

Innovations: Drug Discovery in the Cloud

		Antibiotic Renaissance Antibiotic resistance is one of the most significant challenges to the health care sector in the 21st Century. In this Perspective, Wright discusses how this knowledge is fueling a renaissance of interest and innovation in antibiotic discovery, synthesis, and mechanism that is poised to inform drug discovery to address pressing clinical needs.
		Chemoproteomics to the Rescue An important issue faced by the current drug discovery efforts is how to navigate large genetic information space to produce new first-in-class medicines. In this Perspective, Moellering and Cravatt argue for the critical role of pharmacology in early phases of drug discovery campaigns, and highlight the value of chemoproteomics in this context.
		Systems Biology in Drug Discovery Current drug design strategies often optimize structure of a small molecule to improve the specificity. Although this "one-to-one" approach has been fruitful, adverse drug reactions due to ligand and protein promiscuity have been documented. Brown and Okuno discuss the need to refine the drug design principles and integrate systems biology into the process.
		Computational Drug Discovery Bioinformatics and chemoinformatics approaches contribute to hit discovery, hit-to-lead optimization, safety profiling, target identification and enhance our overall understanding of the health and disease states. The review by Taboureau et al. explores several computational methods used in the field of drug discovery and chemical biology.
		Structural Biology in Drug Discovery Over the past decade researchers have identified features which make drug targets "unligandable". Here, Surade and Blundell discuss challenges of targeting protein-protein interfaces, protein-ligand interactions where adaptive changes are required to configure a binding site, and binding sites with metal ions, high lipophilicity and other features that lead to lack of selectivity.
		Targeting the Orphans The nuclear receptor (NR) superfamily has been a rich source of drug targets for myriad diseases including inflammation, cancer, and metabolic disorders. Here, Burris et al. review recent discoveries that yield important insight into the druggability of three orphan nuclear receptors: RORs, PPARγ, and LRH-1.
		The Power of RNA Over the last three decades RNAs have gone from being viewed as a DNA/protein go-between to key player in regulating cellular function, displaying functional and structural diversity. In this review, Burnett et al. discuss RNA-based therapeutics, their mechanism of action, current state of the development, and challenges faced with moving these drugs to the clinic
		Proteomics in Pre-clinical Drug Discovery The environment in which drugs need to act is extremely complex. In this review, Schirle et al. summarize current status of proteomics in drug discovery, and provide overview of early applications, recent methodological improvements, and how proteomics can be successfully applied in both target-based and phenotype-based workflows for pre-clinical drug discovery to take the complexity head on.
		Finding Drugs in the Sea The world’s marine habitats are rich source of natural products with remarkable chemical diversity. Here, Moore and Gerwick provide a historical perspective of marine natural product research, discuss state of the art efforts, and provide a vision of an exciting future fueled by rapid development of methodology.
		Proteasome Inhibitors Bortezomib is the oldest FDA approved drug that targets proteasome, approved in 2003 for treatment of multiple myeloma. Interest in small molecule proteasome inhibitors has been high ever since. Here, van der Linden et al. review the current state of drug discovery and development aimed at the proteasome as the target.
		Ganging up on Malaria Malaria is a notorious mosquito-borne disease that with a large death burden and economical impact. Here, Guiguemde et al. describe key challenges for currently available chemotherapy and summarize recent success form both academia and industry in applying phenotypic screening campaigns to identify compounds acting on Plasmodium falciparum.