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https://www.readbyqxmd.com/read/28340496/recent-developments-in-nanomedicine-for-melanoma-treatment
#1
REVIEW
Jian-Qin Tang, Xiao-Yang Hou, Chun-Sheng Yang, Ya-Xi Li, Yong Xin, Wen-Wen Guo, Zhi-Ping Wei, Yan-Qun Liu, Guan Jiang
Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340400/pharmacoinformatics-exploration-of-polyphenol-oxidases-leading-to-novel-inhibitors-by-virtual-screening-and-molecular-dynamic-simulation-study
#2
Mubashir Hassan, Qamar Abbas, Zaman Ashraf, Ahmed A Moustafa, Sung-Yum Seo
Polyphenol oxidases (PPOs)/tyrosinases are metal-dependent enzymes and known as important targets for melanogenesis. Although considerable attempts have been conducted to control the melanin-associated diseases by using various inhibitors. However, the exploration of the best anti-melanin inhibitor without side effect still remains a challenge in drug discovery. In present study, protein structure prediction, ligand-based pharmacophore modeling, virtual screening, molecular docking and dynamic simulation study were used to screen the strong novel inhibitor to cure melanogenesis...
March 15, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28340378/current-fda-approved-treatments-for-non-small-cell-lung-cancer-and-potential-biomarkers-for-its-detection
#3
REVIEW
Karla A Ruiz-Ceja, Yolanda I Chirino
BACKGROUND: Lung cancer is the leading worldwide cancer with almost 1.5 million deaths every year. Some drugs for lung cancer treatment have been available on the market for decades, but novel drugs have emerged promising better outcomes, especially for Non-Small Cell Lung Cancer (NSCLC), which represents 75% of lung cancer cases. However, how much do drugs have evolved for NSCLC treatment? Are they sharing the same mechanism of action? AIM: In this review we analyzed how the approved drugs by Federal Drug Agency for NSCLC have advanced in the last four decades identifying shared mechanism of action of medicines against NSCLC treatment and some of the potential biomarkers for early detection...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28339517/omics-studies-their-use-in-diagnosis-and-reclassification-of-sle-and-other-systemic-autoimmune-diseases
#4
Maria Teruel, Chris Chamberlain, Marta E Alarcón-Riquelme
Omics studies of systemic autoimmune diseases (SADs) in general, and SLE in particular, have delivered isolated information from transcriptome, epigenome, genome, cytokine and metabolome analyses. Such analyses have resulted in the identification of disease susceptibility genes and the description of IFN expression signatures, allowing extensive insight into the mechanisms of disease and the development of new therapies. Access to such technologies allows the recognition of patterns of disease at a pathway level, thereby, to reclassify SLE and other SADs and to develop new therapeutics from a personalized perspective...
October 19, 2016: Rheumatology
https://www.readbyqxmd.com/read/28339283/development-optimization-and-implementation-of-a-centralized-metabolic-soft-spot-assay
#5
Anthony A Paiva, Cheryl Klakouski, Shu Li, Benjamin M Johnson, Yue-Zhong Shu, Jonathan Josephs, Tatyana Zvyaga, Ismael Zamora, Wilson Z Shou
AIM: High clearance is a commonly encountered issue in drug discovery. Here we present a centralized metabolic soft spot identification assay with adequate capacity and turnaround time to support the metabolic optimization needs of an entire discovery organization. METHODOLOGY: An integrated quan/qual approach utilizing both an orthogonal sample-pooling methodology and software-assisted structure elucidation was developed to enable the assay. Major metabolic soft spots in liver microsomes (rodent and human) were generated in a batch mode, along with kinetics of parent disappearance and metabolite formation, typically within 1 week of incubation...
March 24, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28339216/embarking-on-a-chemical-space-odyssey
#6
Shiao Y Chow, Adam Nelson
The chemical space explored in drug discovery programs is restricted by a narrow reaction toolkit and the frequent failure of even these reactions with polar and functionalized substrates. Recently, high-throughput reaction optimization has been integrated into discovery workflows, thereby increasing the value of specific reaction classes in the toolkit. It is likely that high-throughput experimentation will enable expansion of the synthetic chemistry that is widely exploited in discovery, thereby increasing innovation in medicinal chemistry...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28339215/discovery-and-pre-clinical-characterization-of-a-3-rd-generation-4-h-heteroaryldihydropyrimidine-hap-analogues-as-hepatitis-b-virus-hbv-capsid-inhibitors
#7
Zongxing Qiu, Xianfeng Lin, Weixing Zhang, Mingwei Zhou, Lei Guo, Buelent Kocer, Guolong Wu, Zhisen Zhang, Haixia Liu, Houguang Shi, Buyu Kou, Taishan Hu, Yimin Hu, Mengwei Huang, S Frank Yan, Zhiheng Xu, Zheng Zhou, Ning Qin, Yue Fen Wang, Shuang Ren, Hongxia Qiu, Yuxia Zhang, Yi Zhang, Xiaoyue Wu, Kai Sun, Sheng Zhong, Jianxun Xie, Giorgio Ottaviani, Yuan Zhou, Lina Zhu, Xiaojun Tian, Liping Shi, Fang Shen, Yi Mao, Xue Zhou, Lu Gao, John A T Young, Jim Zhen Wu, Guang Yang, Alexander V Mayweg, Hong C Shen, Guozhi Tang, Wei Zhu
Described herein are the discovery and structure-activity relationship (SAR) studies of the 3(rd) generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the 1(st) and 2(nd) generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28338341/natural-product-inhibitors-of-carbonic-anhydrase-i-and-ii-isoenzymes-osajin-and-pomiferin
#8
Esra Dilek, Hüseyin Serkan Erol, Ahmet Cakir, Murat Koc, Mesut Bünyami Halici
The aim of this study is to purify carbonic anhydrase I and II isoenzymes from human erythrocyte, isolate two natural products osajin (OSJ) and pomiferin (PMF) from Maclura pomifera fruits, and evaluate the in vitro effect of these natural metabolites on these isoenzymes. These natural products may be used as starting points for drug discovery (like drugs used in several therapeutic applications, including antiglaucoma activity). For the purification procedure, the Sepharose-4B-l-tyrosine-sulphonamide affinity chromatography was used...
March 24, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28338146/a-gold-nanoparticle-mediated-rapid-in-vitro-assay-of-anti-aggregation-reagents-for-amyloid-%C3%AE-and-its-validation
#9
Hye Young Kim, Donghee Lee, Kwon-Yul Ryu, Inhee Choi
Herein, we report a rapid in vitro assay of amyloid β anti-aggregation reagents using gold nanoparticles as nucleation cores and optical reporters. Based on the colorimetric responses observed with the naked eye, effective anti-aggregation reagents were rapidly (<15 min) distinguished. For these reagents, conventional methods showed fewer amyloid β aggregates and an increased viability of neuroblastoma cells after treatment. We envision that our proposed method will facilitate the discovery of efficient drug components for the treatment of Alzheimer's disease...
March 24, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28338050/schisandrin-a-inhibits-dengue-viral-replication-via-upregulating-antiviral-interferon-responses-through-stat-signaling-pathway
#10
Jung-Sheng Yu, Yu-Hsuan Wu, Chin-Kai Tseng, Chun-Kuang Lin, Yao-Chin Hsu, Yen-Hsu Chen, Jin-Ching Lee
Dengue virus (DENV) infects 400 million people worldwide annually. Infection of more than one serotype of DENV highly corresponds to dengue hemorrhagic fever and dengue shock syndrome, which are the leading causes of high mortality. Due to lack of effective vaccines and unavailable therapies against DENV, discovery of anti-DENV agents is urgently needed. We first characterize that Schisandrin A can inhibit the replication of four serotypes of DENV in a concentration- and time-dependent manner, with an effective half-maximal effective concentration 50% (EC50) value of 28...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337796/direct-asymmetric-aza-vinylogous-type-michael-additions-of-nitrones-from-isatins-to-nitroalkenes
#11
Ying-Chun Chen, Gu Zhan, Ming-Lin Shi, Wei-Jia Lin, Yang Ouyang, Wei Du
Nitrones commonly act as 1,3-dipoles and electrophiles to furnish valuable isoxazolidine and N-hydroxyl products, respectively. They also can be converted to nitrone ylide species, and undergo [3+2] formal cycloadditions to access N-hydroxyl pyrrolidines. Here we first present asymmetric direct aza-vinylogous-type additions of nitrones from isatins to nitroalkenes catalyzed by a bifunctional thiourea-tertiary amine, producing highly functionalized nitrones with extended carbon skeletons in excellent stereoselectivity...
March 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28337449/prediction-of-radix-astragali-immunomodulatory-effect-of-cd80-expression-from-chromatograms-by-quantitative-pattern-activity-relationship
#12
Michelle Chun-Har Ng, Tsui-Yan Lau, Kei Fan, Qing-Song Xu, Josiah Poon, Simon K Poon, Mary K Lam, Foo-Tim Chau, Daniel Man-Yuen Sze
The current use of a single chemical component as the representative quality control marker of herbal food supplement is inadequate. In this CD80-Quantitative-Pattern-Activity-Relationship (QPAR) study, we built a bioactivity predictive model that can be applicable for complex mixtures. Through integrating the chemical fingerprinting profiles of the immunomodulating herb Radix Astragali (RA) extracts, and their related biological data of immunological marker CD80 expression on dendritic cells, a chemometric model using the Elastic Net Partial Least Square (EN-PLS) algorithm was established...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337329/antiparasitic-lead-discovery-toward-optimization-of-a-chemotype-with-activity-against-multiple-protozoan-parasites
#13
William Devine, Sarah M Thomas, Jessey Erath, Kelly A Bachovchin, Patricia J Lee, Susan E Leed, Ana Rodriguez, Richard J Sciotti, Kojo Mensa-Wilmot, Michael P Pollastri
Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis present a significant burden across the developing world. Existing therapeutics for these protozoal neglected tropical diseases suffer from severe side effects and toxicity. Previously, NEU-1045 (3) was identified as a promising lead with cross-pathogen activity, though it possessed poor physicochemical properties. We have designed a library of analogues with improved calculated physicochemical properties built on the quinoline scaffold of 3 incorporating small, polar aminoheterocycles in place of the 4-(3-fluorobenzyloxy)aniline substituent...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337325/tetrahydroisoquinoline-7-carboxamide-derivatives-as-new-selective-discoidin-domain-receptor-1-ddr1-inhibitors
#14
Zhen Wang, Yali Zhang, Sergio G Bartual, Jinfeng Luo, Tingting Xu, Wenting Du, Qiuju Xun, Zhengchao Tu, Rolf A Brekken, Xiaomei Ren, Alex N Bullock, Guang Liang, Xiaoyun Lu, Ke Ding
Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release in mouse primary peritoneal macrophages (MPMs)...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337020/delivery-technologies-for-genome-editing
#15
REVIEW
Hao Yin, Kevin J Kauffman, Daniel G Anderson
With the recent development of CRISPR technology, it is becoming increasingly easy to engineer the genome. Genome-editing systems based on CRISPR, as well as transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), are becoming valuable tools for biomedical research, drug discovery and development, and even gene therapy. However, for each of these systems to effectively enter cells of interest and perform their function, efficient and safe delivery technologies are needed. This Review discusses the principles of biomacromolecule delivery and gene editing, examines recent advances and challenges in non-viral and viral delivery methods, and highlights the status of related clinical trials...
March 24, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28336914/inhibition-of-serum-and-glucocorticoid-regulated-kinase-1-as-novel-therapy-for-cardiac-arrhythmia-disorders
#16
Vassilios J Bezzerides, Aifeng Zhang, Ling Xiao, Bridget Simonson, Santosh A Khedkar, Shiro Baba, Filomena Ottaviano, Stacey Lynch, Katherine Hessler, Alan C Rigby, David Milan, Saumya Das, Anthony Rosenzweig
Alterations in sodium flux (INa) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel NaV1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1). Activation of SGK1 in the heart causes a marked increase in both the peak and late sodium currents leading to prolongation of the action potential duration and an increased propensity to arrhythmia...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336474/the-evolution-of-heart-failure-with-reduced-ejection-fraction-pharmacotherapy-what-do-we-have-and-where-are-we-going
#17
REVIEW
Ahmed Selim, Ronald Zolty, Yiannis S Chatzizisis
Cardiovascular diseases represent a leading cause of mortality and increased healthcare expenditure worldwide. Heart failure, which simply describes an inability of the heart to meet the body's needs, is the end point for many other cardiovascular conditions. The last three decades have witnessed significant efforts aiming at the discovery of treatments to improve the survival and quality of life of patients with heart failure; many were successful, while others failed. Given that most of the successes in treating heart failure were achieved in patients with reduced left ventricular ejection fraction (HFrEF), we constructed this review to look at the recent evolution of HFrEF pharmacotherapy...
March 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28336360/gain-a-graph-based-method-to-automatically-analyze-neurite-outgrowth-in-cell-cultures
#18
B L Long, H Li, A Mahadevan, T Tang, K Balotin, N Grandel, J Soto, S Y Wong, A Abrego, S Li, A A Qutub
BACKGROUND: Neurite outgrowth is a metric widely used to assess the success of in vitro neural stem cell differentiation or neuron reprogramming protocols and of high-content screening assays for neural regenerative drug discovery. However, neurite measurements are tedious to perform manually, and there is a paucity of freely available, fully automated software to determine neurite measurements and neuron counting. To provide such a tool to the neurobiology, stem cell, cell engineering, and neuroregenerative communities, we developed an algorithm for performing high-throughput neurite analysis in immunofluorescence images...
March 20, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28336347/solution-conformations-of-a-linked-construct-of-the-zika-virus-ns2b-ns3-protease
#19
Mithun C Mahawaththa, Benjamin J G Pearce, Bim Graham, Christian D Klein, Christoph Nitsche, Gottfried Otting
The Zika virus presents a serious risk for global health. Crystal structures of different constructs of the Zika virus NS2B-NS3 protease (NS2B-NS3pro) have been determined with the aim to provide a basis for rational drug discovery. In these structures, the C-terminal β-hairpin of NS2B, NS2Bc, was observed to be either disordered (open conformation) or bound to NS3pro complementing the substrate binding site (closed conformation). Enzymatically active constructs of flaviviral NS2B-NS3 proteases commonly used for inhibitor testing contain a covalent peptide linker between NS2B and NS3pro...
March 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28335860/-muscling-throughout-life-integrating-studies-of-muscle-development-homeostasis-and-disease-in-zebrafish
#20
Michelle F Goody, Erin V Carter, Elisabeth A Kilroy, Lisa Maves, Clarissa A Henry
The proper development and function of skeletal muscle is vital for health throughout the lifespan. Skeletal muscle function enables posture, breathing, and locomotion; and also impacts systemic processes-such as metabolism, thermoregulation, and immunity. Diseases of skeletal muscle (myopathies, muscular dystrophies) and even some neurological, age-related, and metabolic diseases compromise muscle function and negatively affect health span and quality of life. There have been numerous, recent examples of studies on skeletal muscle development with exciting, therapeutic implications for muscle diseases...
2017: Current Topics in Developmental Biology
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