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Editor-in-Chief: Natalia Ortúzar
Impact Factor: 2.968
ISI Journal Citation Reports © Ranking: 2014: 19/59 (Chemistry Medicinal); 83/255 (Pharmacology & Pharmacy)
Online ISSN: 1860-7187
January 19, 2016
2016 Wolf Prize to Nicolaou and Schreiber
Professors K. C. Nicolaou (Rice University, Department of Chemistry) and Stuart L. Schreiber (Harvard University, Department of Chemistry & Chemical Biology) are this year's recipients of the Wolf Prize in Chemistry.
The Israel Chemical Society will organize a symposium in honor of both laureates on June 1, 2016, which will be hosted by the Schulich Faculty of Chemistry of the Technion — Israel Institute of Technology. The Prize ceremony will take place in the Knesset on the following day, June 2. Read more...
Recently Published Articles
- Fragment Screening of Soluble Epoxide Hydrolase for Lead Generation—Structure-Based Hit Evaluation and Chemistry Exploration
Dr. Yafeng Xue, Dr. Thomas Olsson, Dr. Carina A Johansson, Dr. Linda Öster, Dr. Hans-Georg Beisel, Dr. Mattias Rohman, Dr. David Karis and Dr. Stefan Bäckström
Article first published online: 4 FEB 2016 | DOI: 10.1002/cmdc.201500575
The screening room: Both fragment screening and high-throughput screening are used in an integrated hit-finding and lead-generation strategy. Two distinct scaffolds are identified as tractable starting points for further chemistry work. Significant induced-fit binding is observed for the 2-phenylbenzimidazole-4-sulfonamide compounds. A new lead series may be generated if features from the two series are combined together.
- Structural Re-engineering of the α-Helix Mimetic JY-1-106 into Small Molecules: Disruption of the Mcl-1–Bak-BH3 Protein–Protein Interaction with 2,6-Di-Substituted Nicotinates
Brandon Drennen, Jacob A. Scheenstra, Dr. Jeremy L. Yap, Lijia Chen, Maryanna E. Lanning, Dr. Braden M. Roth, Dr. Paul T. Wilder and Dr. Steven Fletcher
Article first published online: 4 FEB 2016 | DOI: 10.1002/cmdc.201500461
2,6-Di-substituted nicotinates inhibit the myeloid cell leukemia-1 (Mcl-1) oncoprotein with potencies in the single-digit micromolar range, as determined by a fluorescence polarization competition assay. Direct binding to Mcl-1 was confirmed by 2D 1H–15N HSQC NMR spectroscopy. Inspired by a fragment of a previously reported α-helix mimetic, the small-molecules reported herein are more druglike and, owing to greater synthetic accessibility, future optimization is expected to be elementary.
- Substrate Activity Screening (SAS) and Related Approaches in Medicinal Chemistry
Rafaela Gladysz, Prof. Dr. Anne-Marie Lambeir, Dr. Jurgen Joossens, Prof. Dr. Koen Augustyns and Prof. Dr. Pieter Van der Veken
Article first published online: 4 FEB 2016 | DOI: 10.1002/cmdc.201500569
Building on building blocks: SAS is a straightforward fragment-based method with great potential for the design of enzyme inhibitors. A number of aspects require special attention in order to maximize the efficiency of this approach. These include proper design of the substrate library and screening assay, determination of adequate kinetic and thermodynamic substrate parameters, and selection of an appropriate warhead or isostere.
- Cancer Immunotherapy: Selected Targets and Small-Molecule Modulators
Prof. Dr. Hilmar Weinmann
Article first published online: 2 FEB 2016 | DOI: 10.1002/cmdc.201500566
Small molecules for immuno-oncology: Cancer immunotherapy is currently generating a lot of excitement in the scientific community, as well as new hope for many cancer patients given some recent clinical successes. The discovery and development of new small-molecule modulators is a rapidly growing research area for medicinal chemists in immuno-oncology. This review provides a brief introduction into recent trends related to some selected targets and pathways for cancer immunotherapy and their small-molecule pharmacological modulators.
- Fragment-Based Protein–Protein Interaction Antagonists of a Viral Dimeric Protease
Dr. Jonathan E. Gable, Dr. Gregory M. Lee, Dr. Timothy M. Acker, Kaitlin R. Hulce, Eric R. Gonzalez, Dr. Patrick Schweigler, Dr. Samu Melkko, Dr. Christopher J. Farady and Prof. Charles S. Craik
Article first published online: 28 JAN 2016 | DOI: 10.1002/cmdc.201500526
Dimer disruption: Using a fragment-based screen (FBS), we identified several structurally unrelated compounds that inhibit protein–protein interactions of a dimeric human herpesvirus protease. NMR spectroscopy verifies that these fragments bind at or near a hot-spot residue located on the dimer interface. SAR by catalogue discovered analogues with enhanced potency over the primary hits.