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Trends in Pharmacological Sciences

Mehmet Coskun, Severine Vermeire, Ole Haagen Nielsen
Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easily administered therapeutics that may be viable candidates for the management of IBD, such as antibodies against interleukin 6 (IL-6) and IL-12/23, small molecules including Janus kinase inhibitors, antisense oligonucleotide against SMAD7 mRNA, and inhibitors of leukocyte trafficking to intestinal sites of inflammation (e...
December 1, 2016: Trends in Pharmacological Sciences
Matthew L Banks, S Stevens Negus
Substance-use disorders are a global public health problem that arises from behavioral misallocation between drug use and more adaptive behaviors maintained by nondrug alternatives (e.g., food or money). Preclinical drug self-administration procedures that incorporate a concurrently available nondrug reinforcer (e.g., food) provide translationally relevant and distinct dependent measures of behavioral allocation (i.e., to assess the relative reinforcing efficacy of the drug) and behavioral rate (i.e., to assess motor competence)...
December 1, 2016: Trends in Pharmacological Sciences
Susanna Molas, Steven R DeGroot, Rubing Zhao-Shea, Andrew R Tapper
While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal...
November 24, 2016: Trends in Pharmacological Sciences
David G Strauss, Ksenia Blinova
Clinical trials 'in a dish' involve testing medical therapies for safety or effectiveness in the laboratory with human tissue. This has become possible owing to recent biotechnology advances including induced pluripotent stem cells, organs-on-a-chip, and whole-genome sequencing. We provide here an overview of the landscape and highlight steps the FDA is taking to advance the science of clinical trials in a dish and to support the development and validation of new regulatory paradigms to assess drug safety using these new technologies...
November 19, 2016: Trends in Pharmacological Sciences
Dearbhaile C Collins, Raghav Sundar, Joline S J Lim, Timothy A Yap
Precision medicine continues to be the benchmark to which we strive in cancer research. Seeking out actionable aberrations that can be selectively targeted by drug compounds promises to optimize treatment efficacy and minimize toxicity. Utilizing these different targeted agents in combination or in sequence may further delay resistance to treatments and prolong antitumor responses. Remarkable progress in the field of immunotherapy adds another layer of complexity to the management of cancer patients. Corresponding advances in companion biomarker development, novel methods of serial tumor assessments, and innovative trial designs act synergistically to further precision medicine...
November 18, 2016: Trends in Pharmacological Sciences
Manuela S Murgueitio, Christin Rakers, Anne Frank, Gerhard Wolber
As essential proteins of the innate immune system, Toll-like receptors (TLRs) are involved in a plethora of physiological pathologies and their modulation is an ongoing quest in the field of drug discovery. Although TLRs recognize an unusually broad range of different molecular patterns, only a few small-molecule TLR modulators have been reported to date. Recent advances in crystallography and in silico techniques provide promising opportunities for TLR investigations and drug design. Here, three application areas for computational approaches are considered: (i) exploration of TLR structure and activation; (ii) understanding TLR modulation; and (iii) TLR drug discovery...
November 15, 2016: Trends in Pharmacological Sciences
István Gyertyán
Despite the abundance of cognitive enhancer mechanisms identified in basic research, drugs approved for cognitive disorders are scarce and of limited efficacy. Although the so-called 'gold-standard' animal assays are well suited to the study of fundamental learning processes, they fail to predict clinical efficacy against complex and robust cognitive defects. Preclinical validation of potential drug targets requires new approaches with higher translational value. Here I propose a rodent cognitive test system that encompasses several learning paradigms each modeling a certain human cognitive domain...
November 14, 2016: Trends in Pharmacological Sciences
Xiaolan Deng, Yusuke Nakamura
With the accelerating progress in basic and clinical cancer research, a huge body of new discoveries and powerful technologies has allowed us to implement a 'Cancer Precision Medicine (CPM)' system for cancer patients. The CPM system covers a wide range of cancer management including cancer screening, monitoring of relapse/recurrence, selection/prediction of effective drugs/treatments, and personalized immunotherapy. In this system individual cancer patients expect to receive personalized care: an appropriate dose of the right drug at the right time...
November 11, 2016: Trends in Pharmacological Sciences
Robert A Quinn, Louis-Felix Nothias, Oliver Vining, Michael Meehan, Eduardo Esquenazi, Pieter C Dorrestein
Molecular networking is a tandem mass spectrometry (MS/MS) data organizational approach that has been recently introduced in the drug discovery, metabolomics, and medical fields. The chemistry of molecules dictates how they will be fragmented by MS/MS in the gas phase and, therefore, two related molecules are likely to display similar fragment ion spectra. Molecular networking organizes the MS/MS data as a relational spectral network thereby mapping the chemistry that was detected in an MS/MS-based metabolomics experiment...
November 11, 2016: Trends in Pharmacological Sciences
James R Kintzing, Maria V Filsinger Interrante, Jennifer R Cochran
Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity...
November 8, 2016: Trends in Pharmacological Sciences
Richard M O'Connor, Anand Gururajan, Timothy G Dinan, Paul J Kenny, John F Cryan
Current treatment strategies for psychiatric disorders remain inadequate. Impeding development of novel therapeutics is our incomplete knowledge of the molecular pathophysiology underlying these disorders. Changes to miRNA function and expression are increasingly being associated with pathological behavioral states. Furthermore, the prospect of using of miRNA expression profiles (the miRNome) as objective psychiatric diagnosis tools is gaining traction. In this review, we focus on recent findings surrounding the link between miRNA function and psychiatric disorders, and outline some of the key challenges that will need to be overcome if the therapeutic potential of these molecular effectors is to be fully realized...
November 7, 2016: Trends in Pharmacological Sciences
Boris Cvek
No abstract text is available yet for this article.
November 4, 2016: Trends in Pharmacological Sciences
Thomas M Kuntz, Jack A Gilbert
Understanding how individual people respond to medical therapy is a key facet of improving the odds ratio that interventions will have a positive impact. Reducing the non-responder rate for an intervention or reducing complications associated with a particular treatment or surgery is the next stage of medical advance. The Precision Medicine Initiative, launched in January 2015, set the stage for enhanced collaboration between researchers and medical professionals to develop next-generation techniques to aid patient treatment and recovery, and increased the opportunities for impactful pre-emptive care...
October 25, 2016: Trends in Pharmacological Sciences
Nicholas C Dracopoli, Mark S Boguski
Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved. The great majority of CDx tests are for drugs that inhibit signal transduction pathways by either inhibiting the intracellular kinase activity with a small molecule or preventing ligand-induced receptor activation with a monoclonal antibody. In most of these cases, prospective patient selection for the biomarker-positive subpopulation was initiated in or before Phase II...
October 24, 2016: Trends in Pharmacological Sciences
B Vijayalakshmi Ayyar, Sushrut Arora, Richard O'Kennedy
Antibody-based therapies have garnered considerable success in recent years. This is due to the availability of strategies to successfully engineer antibodies into humanized forms, better understanding of the biological processes involved in cancer development, the availability of novel recombinant antibody formats, better antibody selection platforms, and improved antibody conjugation methodologies. Such achievements have led to an explosion in the generation of antibodies and antibody-associated constructs for the treatment of cancer and other diseases...
October 10, 2016: Trends in Pharmacological Sciences
Jin Xiang, Eugene Chun, Chang Liu, Liang Jing, Zina Al-Sahouri, Lan Zhu, Wei Liu
G protein-coupled receptors (GPCRs) constitute the largest class of drug targets in the human genome, which highlights the importance of understanding the molecular basis of their activation, downstream signaling, and regulation. Since 2007, great progress has been made in the field of GPCR structure determination and their signaling complexes at the molecular level. Here, we summarize the high-resolution structures of over 30 different GPCRs with their co-crystallized ligands, and outline the successful strategies involved, including construct design, expression systems, and lipidic cubic phase (LCP) composition, and the many key technical parameters of the crystallization methods...
October 7, 2016: Trends in Pharmacological Sciences
Meghan J Chenoweth, Rachel F Tyndale
Worldwide, approximately one billion people smoke cigarettes. Cigarette smoking persists in part because long-term smoking cessation rates are modest on existing treatments. Smoking cessation outcomes are influenced by genetic factors, including genetic variation in enzymes that metabolize nicotine and smoking cessation medications, as well as in receptor targets for nicotine and treatment medications. For example, smokers with genetically slow nicotine metabolism have higher cessation success on behavioural counseling and nicotine patches compared with smokers with genetically fast nicotine metabolism...
October 3, 2016: Trends in Pharmacological Sciences
Kristin Ingolfsdottir
Recent developments confirm predictions by the IEEE that Massive Open Online Courses (MOOCs) will have extensive impact on the future landscape of higher education. New degree structures are being introduced and awarding of verified MOOC credentials is becoming more widespread, as is recognition of MOOC credits by universities and employers. The question is whether this disruptive influence is being sufficiently used as an incentive for re-evaluation of standard practices and for driving strategic change in higher education...
September 29, 2016: Trends in Pharmacological Sciences
Jacob P R Jacobsen, Andrew D Krystal, K Ranga R Krishnan, Marc G Caron
Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need. Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP) safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; however, 5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics...
September 28, 2016: Trends in Pharmacological Sciences
Catherine M Cahill, Wendy Walwyn, Anna M W Taylor, Amynah A A Pradhan, Christopher J Evans
Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry...
September 23, 2016: Trends in Pharmacological Sciences
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