Current Topics in Medicinal Chemistry - Volume 14, Issue 3, 2014

The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers Read More

This article describes the unique industrial - academic collaboration that has been running for four years between Janssen Pharmaceutica NV and the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) towards identifying the next generation of schizophrenia therapeutics. This was a true collaboration, with both entities engaged in chemistry, In vitro pharmacology, DMPK and In vivo behavioral pharmacology, and alig Read More

The business model for medical therapy development has changed drastically. Large companies that once conducted their own Research and Development (R&D) and funded all the preclinical studies, all phases of clinical development and marketing of the products are increasingly turning to others for more and more of the earlier work in hopes of being able to in-license a de-risked program well downstream, take it throug Read More

Partnerships between industry and academia are becoming increasingly complex and relevant in the drive to discover innovative new medicines. We describe the structure of the collaboration between the University of California – San Francisco – Small Molecule Discovery Center (UCSF-SMDC) and Genentech to develop chemical matter that inhibits the activity of caspase-6. We focus on the scientific basis for the partnership an Read More

The National Institutes of Health (NIH), academic medical centers and industry have a long and productive history in collaborating together. Decreasing R&D budgets in both the private and public sector have made the need for such collaborations paramount to reduce the risk of further declines in the number of innovative drugs reaching the market to address pressing public health needs. Doing more with less has force Read More

In 2010, the National Institutes of Health (NIH) established the Therapeutics for Rare and Neglected Diseases (TRND) program within the National Center for Advancing Translational Sciences (NCATS), which was created to stimulate drug discovery and development for rare and neglected tropical diseases through a collaborative model between the NIH, academic scientists, nonprofit organizations, and pharmaceutical and Read More

To catalyze research on historically untargeted protein kinases, we created the PKIS, an annotated set of 367 small molecule kinase inhibitors. The set has been widely distributed to academic collaborators as an open access tool. It has been used to identify chemical starting points for development of chemical probes for orphan kinases and to investigate kinase signaling in high content phenotypic assays. Access to the Read More

Biological systems are not only controlled by the abundance of individual proteins, but also by the formation of complexes and the dynamics of protein-protein interactions. The identification of the components of protein complexes can be obtained by shotgun proteomics using affinity purification coupled to mass spectrometry. Such studies include the analyses of several samples and experimental controls in order to di Read More

Interferons (IFNs) are proteins of the family of cytokines. Their antiproliferative function has been taken into account for several clinical therapies against malignant diseases. In this family, IFNs α and γ have demonstrated the highest antitumor effects. HerberPAG® is a new co-formulation with IFNs, α2b and γ. It has been obtained to increase the antiproliferative effect of individual IFNs and decrease their associated toxicity. Glio Read More

Breast cancer is the leading cause of cancer related deaths in women. Most breast cancers stem from mammary ductal cells that secrete nipple aspirate fluid (NAF), a biological sample that contains proteins associated with the tumor microenvironment. In this study, NAF samples from both breasts of 7 Brazilian patients with unilateral breast cancer were analyzed. These samples were systematically compared using sodium Read More

The numerous efforts invested in the identification of biomarkers for neurodegenerative and neuropsychiatric disorders, such as Parkinson’s disease and schizophrenia, are justified because these disorders affect several million people worldwide. Although genetic implications and the role of the environment have been shown in the progression of those disorders, together with anatomical and neurochemical characteristics Read More

Melanoma is the third most common brain metastasis cause in the United States as it has a relatively high susceptibility to metastasize to the central nervous system. Among the different origins for brain metastasis, those originating from primary gastric melanomas are extremely rare. Here, we compare protein profiles obtained from formalin-fixed paraffin- embedded (FFPE) tissues of a primary gastric melanoma with i Read More

The field of proteomics has grown vertiginously in the last years. This has been due fundamentally to technological improvements in the instrumentation, methods, and easy-to-use software, thereby making it possible to address a large number of biological questions and to deepen the study of the proteome of several organisms. The development in the field has imposed a challenge in the computational analysis of Read More

The emergence of new DNA sequencing technologies has allowed an exponential growth of genomic and transcriptomic data that ultimately yielded important results to several areas such as medicine and biology. This continuous technological progress presents several advantages and caveats that have to be considered for each new method. In this review, we describe the so-called second and third generation DNA seq Read More

The right estimation of the evolutionary distance between DNA or protein sequences is the cornerstone of the current phylogenetic analysis based on distance methods. Herein, it is demonstrated that the Manhattan distance (dw), weighted by the evolutionary importance of the nucleotide bases in the codon, is a naturally derived metric in the standard genetic code cube inserted into the three-dimensional Euclidean space. Read More

Over the past decades DNA sequencing technologies have been improving in aspects like quality, read length, runtimes and yields, all at a lower cost. Despite these improvements, genome assembly remains a challenge in genome sequencing projects, especially when different sequencing platforms are used. At the present, there is no program that can handle and assemble different sequencing technologies better than sp Read More

Since the advent of high-throughput DNA sequencing technologies, the ever-increasing rate at which genomes have been published has generated new challenges notably at the level of genome annotation. Even if gene predictors and annotation softwares are more and more efficient, the ultimate validation is still in the observation of predicted gene product( s). Mass-spectrometry based proteomics provides the necessary Read More

Proteins are the principal mediators of the functions in the cell; therefore, any abnormal variations on their abundance levels may reflect the presence of pathological processes. In this sense, many researchers rely on the functional interpretation of protein lists generated by quantitative proteomics experiments to analyze, for instance, these variations in the context of diseases´ molecular basis and drug discovery. Since Read More