Small-molecule modulation of protein–protein interactions
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Christian Ottmann (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Molecular crime scene investigation – dusting for fingerprints
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Jürgen Bajorath In chemoinformatics and drug design, fingerprints (FPs) are defined as string representations of molecular structure and properties and are popular descriptors for similarity searching. FPs are generally characterized by the simplicity of their design and ease of use. Despite a long history in chemoinformatics, the potential and limitations of FP searching are often not well understood. Standard FPs can also be subjected to engineering techniques to tune them for specific search applications. (Sour...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Scaffold variations in amine warhead of histamine H3 receptor antagonists
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Kerstin Wingen , Holger Stark The histamine H3 receptor (H3R) is involved in numerous regulatory neurotransmission processes and therefore, is a prominent target for centrally occurring disease with some promising clinical candidates. Previous research resulted in the identification of a core pharmacophore blueprint for H3R antagonists/inverse agonists, which when inserted in a molecule, mostly ensures acceptable affinity. Nevertheless, variations of scaffold and peripheral areas can increase potency and pharmacok...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Molecular topology – dissimilar similarities
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Jorge Galvez , Maria Galvez-Llompart , Riccardo Zanni , Ramon Garcia-Domenech The present paper depicts the role of molecular topology in the study of similarity–dissimilarity between molecular structures. It proves that molecular topology represents a very useful tool for getting common patterns of pharmacological activity and hence an efficient approach for the search of novel lead drugs. (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
De-peptidising protein–protein interactions – big jobs for small molecules
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Darren Fayne Virtually all biological processes rely on protein–protein interactions (PPIs) for signal propagation, therefore representing a vast array of potentially viable therapeutic intervention points. Targeting PPIs is a relatively novel drug development strategy so computational approaches towards analysing the interface between protein partners and predicting the likelihood of developing a small molecule inhibitor are still progressing. This review provides an overview of recent successful examples of com...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Building in molecular diversity for targeted libraries
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): David W. Sheppard , Jacqueline A. MacRitchie The use of gene-focussed libraries for screening against protein targets can improve timelines for drug discovery projects. This is especially true when the library is based on a novel core scaffold, avoiding the potential need to scaffold hop from early hits. Identification of an appropriate novel scaffold is therefore integral to the success of such a library. In this article we outline a new method to aid scaffold design that combines structure-based virtual screenin...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
De novo design – hop(p)ing against hope
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Gisbert Schneider Current trends in computational de novo design provide a fresh approach to ‘scaffold-hopping’ in drug discovery. The methodological repertoire is no longer limited to receptor-based methods, but specifically ligand-based techniques that consider multiple properties in parallel, including the synthetic feasibility of the computer-generated molecules and their polypharmacology, provide innovative ideas for the discovery of new chemical entities. The concept of fragment-based and virtual reaction...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Approaches to Scaffold Hopping
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): David G. Lloyd (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
A need for new generation antibiotics against MRSA resistant bacteria
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Cornelia Pasberg-Gauhl New antibiotics are highly needed due to continuously emerging resistances, in particular for methicillin-resistant Staphylococcus aureus (MRSA). Only a few new generation antibiotics with new mechanisms of action are available or in development in the recent years. Promising emerging drug candidates with a new mechanism of action are the synthetic guanidine-based polymers based on Akacid. They are highly potent against a wide range of microorganisms and have a beneficial safety profile as reflected in t...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Overcoming drug resistance through in silico prediction
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Pablo Carbonell , Jean-Yves Trosset Prediction tools are commonly used in pre-clinical research to assist target selection, to optimize drug potency or to predict the pharmacological profile of drug candidates. In silico prediction and overcoming drug resistance is a new opportunity that creates a high interest in pharmaceutical research. This review presents two main in silico strategies to meet this challenge: a structure-based approach to study the influence of mutations on the drug-target interaction and a system-biology ...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Current aspects in resistance against tyrosine kinase inhibitors in chronic myelogenous leukemia
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Stefan Balabanov , Melanie Braig , Tim H. Brümmendorf Resistance against tyrosine kinase inhibitors (TKIs) represents a relevant clinical problem in treatment of chronic myelogenous leukemia (CML). On the basis of their activity against the spectrum of BCR-ABL mutations that have shown to be the most prominent mechanism of resistance to imatinib, new TKIs have been classified as second generation (such as nilotinib, dasatinib and bosutinib) or third generation (also covering T315I such as ponatinib) TKIs. However, mutations...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Antimalarial drug resistance: new treatments options for Plasmodium
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Francisco-Javier Gamo Malaria is one of the world's most deadly infectious diseases. Millions of lives are threatened by the continued development of resistance in the malaria parasite which is overcoming the effectiveness of current antimalarial treatments. The scientific community is facing this challenge by developing new and superior therapies to combat, and potentially eradicate, this wide spread plague. New anti-Plasmodium agents derived from phenotypic screening hits (e.g. spiroindolones) or from target based projects (...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Resistance to minor groove binders
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Benedetta Colmegna , Sarah Uboldi , Eugenio Erba , Maurizio D’Incalci In this paper multiple resistance mechanisms to minor groove binders (MGBs) are overviewed. MGBs with antitumor properties are natural products or their derivatives and, as expected, they are all substrates of P-glycoprotein (P-gp). However, a moderate expression of P-gp does not appear to reduce the sensitivity to trabectedin, the only MGB so far approved for clinical use. Resistance to this drug is often related to transcriptional mechanisms and to DN...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Overcoming antifungal resistance
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Anand Srinivasan , Jose L. Lopez-Ribot , Anand K. Ramasubramanian Fungal infections have become one of the major causes of morbidity and mortality in immunocompromised patients. Despite increased awareness and improved treatment strategies, the frequent development of resistance to the antifungal drugs used in clinical settings contributes to the increasing toll of mycoses. Although a natural phenomenon, antifungal drug resistance can compromise advances in the development of effective diagnostic techniques and novel antifun...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Personalized HIV therapy to control drug resistance
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Thomas Lengauer , Nico Pfeifer , Rolf Kaiser The therapy of HIV patients is characterized by both the high genomic diversity of the virus population harbored by the patient and a substantial volume of therapy options. The virus population is unique for each patient and time point. The large number of therapy options makes it difficult to select an optimal or near optimal therapy, especially with therapy-experienced patients. In the past decade, computer-based support for therapy selection, which assesses the level of viral r...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
