Targets

Stay on target - p193

doi:10.1038/nchembio.1226

Applying a rigorous chemical biology approach to the selection and validation of clinical targets will increase the success of drug discovery initiatives.

Full Text - Stay on target | PDF (75 KB) - Stay on target

Targets

Target validation using chemical probes - pp195 - 199

Mark E Bunnage, Eugene L Piatnitski Chekler & Lyn H Jones

doi:10.1038/nchembio.1197

Fully profiled chemical probes are essential to support the unbiased interpretation of biological experiments necessary for rigorous preclinical target validation. We believe that by developing a 'chemical probe tool kit', and a framework for its use, chemical biology can have a more central role in identifying targets of potential relevance to disease, avoiding many of the biases that complicate target validation as practiced currently.

Full Text - Target validation using chemical probes | PDF (716 KB) - Target validation using chemical probes

Targets

Determining target engagement in living systems - pp200 - 205

Gabriel M Simon, Micah J Niphakis & Benjamin F Cravatt

doi:10.1038/nchembio.1211

Chemical probes are critical tools for elucidating the biological functions of proteins and can lead to new medicines for treating disease. The pharmacological validation of protein function requires verification that chemical probes engage their intended targets in vivo. Here we discuss technologies, both established and emergent, for measuring target engagement in living systems and propose that determining this parameter should become standard practice for chemical probe and drug discovery programs.

Full Text - Determining target engagement in living systems | PDF (649 KB) - Determining target engagement in living systems

Targets

The why and how of phenotypic small-molecule screens - pp206 - 209

Ulrike S Eggert

doi:10.1038/nchembio.1206

Small-molecule phenotypic screening has high potential in the discovery of new chemical probes and new biological small-molecule targets. This commentary will discuss the basic principles underlying the design of phenotypic screens and propose some guidelines to facilitate the discovery of small molecules from phenotypic screens.

Full Text - The why and how of phenotypic small-molecule screens | PDF (212 KB) - The why and how of phenotypic small-molecule screens

Targets

Translational synthetic chemistry - pp210 - 213

Sarathy Kesavan & Lisa A Marcaurelle

doi:10.1038/nchembio.1207

Providing chemical matter to modulate newly identified biological targets—as well as pre-existing but chemically intractable ones—remains a challenge in the discovery of therapeutics. Here, we discuss opportunities for synthetic chemists to make a direct impact in addressing targets that are considered 'undruggable'.

Full Text - Translational synthetic chemistry | PDF (385 KB) - Translational synthetic chemistry

Targets

Systems-level antimicrobial drug and drug synergy discovery - pp222 - 231

Terry Roemer & Charles Boone

doi:10.1038/nchembio.1205

Abstract - Systems-level antimicrobial drug and drug synergy discovery | Full Text - Systems-level antimicrobial drug and drug synergy discovery | PDF (868 KB) - Systems-level antimicrobial drug and drug synergy discovery

Targets

Target identification and mechanism of action in chemical biology and drug discovery - pp232 - 240

Monica Schenone, Vlado Dančík, Bridget K Wagner & Paul A Clemons

doi:10.1038/nchembio.1199

Abstract - Target identification and mechanism of action in chemical biology and drug discovery | Full Text - Target identification and mechanism of action in chemical biology and drug discovery | PDF (1.40 MB) - Target identification and mechanism of action in chemical biology and drug discovery