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https://www.readbyqxmd.com/read/28346821/structure-activity-relationships-on-cynnamoyl-derivatives-as-inhibitors-of-p300-histone-acetyltransferase
#1
Valentina Noemi Madia, Rosaria Benedetti, Maria Letizia Barreca, Liza Ngo, Luca Pescatori, Antonella Messore, Giovanni Pupo, Francesco Saccoliti, Sergio Valente, Antonello Mai, Luigi Scipione, Yujun George Zheng, Cristina Tintori, Maurizio Botta, Violetta Cecchetti, Lucia Altucci, Roberto Di Santo, Roberta Costi
Human p300 is a polyhedric transcriptional coactivator, playing a crucial role by acetylating histones on specific lysine residues. A great deal of evidences shows that p300 is involved in several diseases as leukemia, tumors and viral infection. Its involvement in pleiotropic biological roles and connections to diseases provide the rationale as to how its modulation could represent an amenable drug target. Several p300 inhibitors (HATi) have been described so far, but all suffer from low potency, lack of specificity or low cell-permeability, highlighting the need to find more effective inhibitors...
March 27, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28346810/an-automated-multiplexed-hepatotoxicity-and-cyp-induction-assay-using-heparg-cells-in-2d-and-3d
#2
Lindsey M Ott, Karthik Ramachandran, Lisa Stehno-Bittel
Drug-induced liver injury (DILI) and drug-drug interactions (DDIs) are concerns when developing safe and efficacious compounds. We have developed an automated multiplex assay to detect hepatotoxicity (i.e., ATP depletion) and metabolism (i.e., cytochrome P450 1A [CYP1A] and cytochrome P450 3A4 [CYP3A4] enzyme activity) in two-dimensional (2D) and three-dimensional (3D) cell cultures. HepaRG cells were cultured in our proprietary micromold plates and produced spheroids. HepaRG cells, in 2D or 3D, expressed liver-specific proteins throughout the culture period, although 3D cultures consistently exhibited higher albumin secretion and CYP1A/CYP3A4 enzyme activity than 2D cultures...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346764/mapping-the-interactions-of-selective-biochemical-probes-of-antibody-conformation-by-hydrogen-deuterium-exchange-mass-spectrometry
#3
Ulrike Leurs, Hermann Beck, Lea Bonnington, Ingo Lindner, Ewa Pol, Kasper Dyrberg Rand
Protein-based pharmaceuticals represent the fastest growing group of drugs in development in the pharmaceutical industry. One of the major challenges in the discovery, development and distribution of biopharmaceuticals is the assessment of changes in their higher-order structure due to chemical modifications. Here, we investigate the interactions of three different biochemical probes (Fabs) generated to detect conformational changes in a therapeutic IgG1 antibody (mAbX) by local hydrogen-deuterium exchange mass spectrometry (HDX-MS)...
March 27, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28346390/the-effect-and-mechanism-of-transdermal-penetration-enhancement-of-fu-s-cupping-therapy-new-physical-penetration-technology-for-transdermal-administration-with-traditional-chinese-medicine-tcm-characteristics
#4
Wei-Jie Xie, Yong-Ping Zhang, Jian Xu, Xiao-Bo Sun, Fang-Fang Yang
BACKGROUND: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. METHODS: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346305/a-case-approach-to-perioperative-drug-drug-interactions
#5
Eugenia Yiannakopoulou
No abstract text is available yet for this article.
March 24, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28346104/bioengineered-3d-glial-cell-culture-systems-and-applications-for-neurodegeneration-and-neuroinflammation
#6
P Marc D Watson, Edel Kavanagh, Gary Allenby, Matthew Vassey
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346097/an-optimized-3d-coculture-assay-for-preclinical-testing-of-pro-and-antiangiogenic-drugs
#7
Daniela Unterleuthner, Nina Kramer, Karoline Pudelko, Alexandra Burian, Markus Hengstschläger, Helmut Dolznig
Angiogenesis is a promising target for anticancer therapies, but also for treating other diseases with pathologic vessel development. Targeting the vascular endothelial growth factor (VEGF) pathway did not proof as effective as expected due to emerging intrinsic resistance mechanisms, as well as stromal contributions leading to drug insensitivity. Therefore, alternative strategies affecting the interaction of endothelial cells (ECs) with other stromal cells seem to be more promising. Human preclinical in vitro angiogenesis models successfully recapitulating these interactions are rare, and two-dimensional (2D) cell cultures cannot mimic tissue architecture in vivo...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346018/antiretroviral-treatment-in-hiv-infected-children-who-require-a-rifamycin-containing-regimen-for-tuberculosis
#8
Helena Rabie, Eric H Decloedt, Anthony J Garcia-Prats, Mark F Cotton, Lisa Frigati, Marc Lallemant, Anneke Hesseling, H Simon Schaaf
In high prevalence settings, tuberculosis and HIV dual infection and co-treatment is frequent. Rifamycins, especially rifampicin, in combination with isoniazid, ethambutol and pyrazinamide are key components of short-course antituberculosis therapy. Areas covered: We reviewed available data, for which articles were identified by a Pubmed search, on rifamycin-antiretroviral interactions in HIV-infected children. Rifamycins have potent inducing effects on phase I and II drug metabolising enzymes and transporters...
March 27, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28345929/utility-of-cyp3a4-and-pxr-car-cyp3a4-3a7-transgenic-mouse-models-to-assess-the-magnitude-of-cyp3a4-mediated-drug-drug-interactions
#9
Justin Q Ly, Kirsten Messick, Ann Qin, Ryan H Takahashi, Edna F Choo
Species differences in the expression, activity, regulation and substrate specificity of metabolizing enzymes preclude the use of animal models to predict clinical drug-drug interactions (DDI). The objective of this work is to determine if the transgenic (Tg) Cyp3a-/-Tg-3A4Hep/Int and Nr1i2/Nr1i3-/--Cyp3a-/-Tg-PXR-CAR-3A4/3A7Hep/Int (PXR-CAR-CYP3A4/3A7) mouse models could be used to predict in vivo DDI of 10 drugs; alprazolam, bosutinib, crizotinib, dasatinib, gefitinib, ibrutinib, regorafenib, sorafenib, triazolam, and vandetinib (as victims), with varying magnitudes of reported CYP3A4 clinical DDI...
March 27, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28345916/molecular-mechanism-of-nucleotide-dependent-allosteric-regulation-in-amp-activated-protein-kinase
#10
Navjeet Ahalawat, Rajesh Kumar Murarka
The AMP-activated protein kinase (AMPK), a central enzyme in the regulation of energy homeostasis, is an important drug target for type 2 diabetes, obesity and cancer. Binding of adenosine nucleotides to the regulatory γ-subunit tightly regulates the activity of this enzyme. Though recent crystal structures of AMPK have provided important insights into the allosteric activation of AMPK, molecular details of the regulatory mechanism of AMPK activation is still elusive. Here, we have performed extensive all-atom molecular dynamics (MD) simulations and shown that the kinase domain (KD) and γ-subunit comes closer resulting in a more compact heterotrimeric AMPK complex in AMP-bound state compared to the ATP-bound state...
March 27, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28345876/engineering-cellular-microenvironments-with-photo-and-enzymatically-responsive-hydrogels-toward-biomimetic-3d-cell-culture-models
#11
Roger Y Tam, Laura J Smith, Molly S Shoichet
Conventional cell culture techniques using 2D polystyrene or glass have provided great insight into key biochemical mechanisms responsible for cellular events such as cell proliferation, differentiation, and cell-cell interactions. However, the physical and chemical properties of 2D culture in vitro are dramatically different than those found in the native cellular microenvironment in vivo. Cells grown on 2D substrates differ significantly from those grown in vivo, and this explains, in part, why many promising drug candidates discovered through in vitro drug screening assays fail when they are translated to in vivo animal or human models...
March 27, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28345866/biocompatible-hydroxylated-boron-nitride-nanosheets-polyvinyl-alcohol-interpenetrating-hydrogels-with-enhanced-mechanical-and-thermal-responses
#12
Lin Jing, Hongling Li, Roland Yingjie Tay, Bo Sun, Siu Hon Tsang, Olivier Cometto, Jinjun Lin, Edwin Hang Tong Teo, Alfred Iing Yoong Tok
Polyvinyl alcohol (PVA) hydrogels with tissue-like viscoelasticity, excellent biocompatibility and high hydrophilicity have been considered as promising cartilage replacement materials. However, lack of sufficient mechanical properties is a critical barrier to their usage as load-bearing cartilage substitutes. Herein, we report hydroxylated boron nitride nanosheets (OH-BNNS)/PVA interpenetrating hydrogels by cyclically freezing/thawing the aqueous mixture of PVA and highly hydrophilic OH-BNNS (up to 0.6 mg/mL, two times the highest reported so far)...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28345742/a-qualitative-exploration-of-chronic-pain-and-opioid-treatment-among-hiv-patients-with-drug-use-disorders
#13
Sarina R Isenberg, Allysha C Maragh-Bass, Kathleen Ridgeway, Mary C Beach, Amy R Knowlton
OBJECTIVE: The study explored high-risk participants' experiences with pain management regarding clinical access to and use of prescription opioids. DESIGN: Qualitative semistructured interviews and focus groups. SETTING: Data were collected August 2014 to May 2015 at an urban community-based research facility in Baltimore City, MD. PARTICIPANTS: HIV participants with chronic pain and a history of illicit drug use. METHODS: Qualitative coding and analysis used an iterative, inductive, and thematic approach and coders achieved inter-coder consistency...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28345368/sponsors-and-investigative-staffs-perceptions-of-the-current-investigational-new-drug-safety-reporting-process-in-oncology-trials
#14
Raymond Perez, Patrick Archdeacon, Nancy Roach, Robert Goodwin, Jonathan Jarow, Nina Stuccio, Annemarie Forrest
BACKGROUND/AIMS: The Food and Drug Administration's final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes...
March 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28345306/the-burden-and-management-of-cytochrome-p450-2d6-cyp2d6-mediated-drug-drug-interaction-ddi-co-medication-of-metoprolol-and-paroxetine-or-fluoxetine-in-the-elderly
#15
Muh Akbar Bahar, Eelko Hak, Jens H J Bos, Sander D Borgsteede, Bob Wilffert
PURPOSE: Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of metoprolol-paroxetine/fluoxetine interaction in the elderly and how these interactions are managed in Dutch community pharmacies. METHOD: Dispensing data were collected from the University of Groningen pharmacy database (IADB...
March 26, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28345177/pharmacogenomics-of-off-target-adrs
#16
REVIEW
Sarah L Garon, Rebecca K Pavlos, Katie D White, Nancy J Brown, Cosby A Stone, Elizabeth J Phillips
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory although they can manifest with a variety of shared clinical features including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus, and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programs for their prevention...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28344933/precision-medicine-the-golden-gate-for-detection-treatment-and-prevention-of-alzheimer-s-disease
#17
H Hampel, S E O'Bryant, J I Castrillo, C Ritchie, K Rojkova, K Broich, N Benda, R Nisticò, R A Frank, B Dubois, V Escott-Price, S Lista
During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy...
December 2016: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/28344923/impact-of-drug-treatment-at-neonatal-ages-on-variability-of-drug-metabolism-and-drug-drug-interactions-in-adult-life
#18
Stephanie Piekos, Chad Pope, Austin Ferrara, Xiao-Bo Zhong
PURPOSE OF REVIEW: As the number of patients taking more than one medication concurrently continues to increase, predicting and preventing drug-drug interactions (DDIs) is now more important than ever. Administration of one drug can cause changes in the expression and activity of drug metabolizing enzymes (DMEs) and alter the efficacy or toxicity of other medications that are substrates for these enzymes, resulting in a DDI. In today's medical practice, potential DDIs are evaluated based on the current medications a patient is taking with little regard to drugs the patient has been exposed to in the past...
February 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28344755/effect-of-topical-application-of-nigella-sativa-oil-and-oral-acetaminophen-on-pain-in-elderly-with-knee-osteoarthritis-a-crossover-clinical-trial
#19
Akram Kooshki, Reza Forouzan, Mohammad Hassan Rakhshani, Maryam Mohammadi
BACKGROUND: Limited evidence supports Nigella sativa's role as an effective complementary and alternative medicine and the anti-inflammatory effects of Nigella sativa on patients with allergic rhinitis. OBJECTIVE: The aim of this study was to investigate the effect of topical application of Nigella sativa oil and oral acetaminophen on pain in the elderly with knee osteoarthritis residing in a parents' home in Sabzevar. METHODS: This study is done as a crossover clinical trial...
November 2016: Electronic Physician
https://www.readbyqxmd.com/read/28344466/an-overview-of-pharmacodynamic-modelling-ligand-binding-approach-and-its-application-in-clinical-practice
#20
REVIEW
Mohammed Saji Salahudeen, Prasad S Nishtala
The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect ([Formula: see text]) of a drug as a function of the drug concentration ([Formula: see text]) and estimate an unknown PD parameter ([Formula: see text]). The PD models have been described as fixed, linear, log-linear, [Formula: see text], sigmoid [Formula: see text], and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
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