keyword
MENU ▼
Read by QxMD icon Read
search

Targetted small molecules

keyword
https://www.readbyqxmd.com/read/28347131/preclinical-in-vivo-cancer-straightway-to-patients
#1
Marion de Jong, Stephen Mather, Theodosia Maina
Detection of useful cellular targets has strongly stimulated personalized tumor-targeted imaging and therapy approaches, also involving synthesis and evaluation of nuclear imaging probes with potential for clinical applications. Reviews of preclinical and translational studies concerning such probes, including radiolabeled antibodies, nanobodies, affibodies, peptides, small molecule inhibitors, and nanoparticles, are presented in this issue. As most tracers described in these articles have been developed for the field of cancer imaging and radionuclide therapy, the current article on preclinical studies will focus on cancer research as well...
June 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28346812/identification-of-a-novel-benzimidazole-pyrazolone-scaffold-that-inhibits-kdm4-lysine-demethylases-and-reduces-proliferation-of-prostate-cancer-cells
#2
David M Carter, Edgar Specker, Jessica Przygodda, Martin Neuenschwander, Jens Peter von Kries, Udo Heinemann, Marc Nazaré, Ulrich Gohlke
Human lysine demethylase (KDM) enzymes (KDM1-7) constitute an emerging class of therapeutic targets, with activities that support growth and development of metastatic disease. By interacting with and co-activating the androgen receptor, the KDM4 subfamily (KDM4A-E) promotes aggressive phenotypes of prostate cancer (PCa). Knockdown of KDM4 expression or inhibition of KDM4 enzyme activity reduces the proliferation of PCa cell lines and highlights inhibition of lysine demethylation as a possible therapeutic method for PCa treatment...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346786/break-down-in-order-to-build-up-decomposing-small-molecules-for-fragment-based-drug-design-with-emolfrag
#3
Tairan Liu, Misagh Naderi, Chris Alvin, Supratik Mukhopadhyay, Michal Brylinski
Constructing high-quality libraries of molecular building blocks is essential for successful fragment-based drug discovery. In this communication, we describe eMolFrag, a new open-source software to decompose organic compounds into non-redundant fragments retaining molecular connectivity information. Given a collection of molecules, eMolFrag generates a set of unique fragments comprising larger moieties, bricks, and smaller linkers connecting bricks. These building blocks can subsequently be used to construct virtual screening libraries for targeted drug discovery...
March 27, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28346741/small-molecules-targeting-human-n-acetylmannosamine-kinase
#4
Stephan Hinderlich, Martin Neuenschwander, Paul-Robin Wratil, Andreas Oder, Michael Lisurek, Long D Nguyen, Jens Peter von Kries, Christian Hackenberger
N-Acetylmannosamine kinase (MNK) plays a key role in the biosynthesis of sialic acids and glycosylation of proteins. Sialylated glycoconjugates affect a large number of biological processes, including immune modulation and cancer transformation. For the search of effective inhibitors of MNK we applied high-throughput screening of drug-like small molecules. Applying different orthogonal assays for their validation we identified four potential MNK-specific inhibitors with IC50 values in the low micromolar range...
March 27, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28346540/fragment-library-screening-identifies-hits-that-bind-to-the-non-catalytic-surface-of-pseudomonas-aeruginosa-dsba1
#5
Biswaranjan Mohanty, Kieran Rimmer, Róisín M McMahon, Stephen J Headey, Mansha Vazirani, Stephen R Shouldice, Mathieu Coinçon, Stephanie Tay, Craig J Morton, Jamie S Simpson, Jennifer L Martin, Martin J Scanlon
At a time when the antibiotic drug discovery pipeline has stalled, antibiotic resistance is accelerating with catastrophic implications for our ability to treat bacterial infections. Globally we face the prospect of a future when common infections can once again kill. Anti-virulence approaches that target the capacity of the bacterium to cause disease rather than the growth or survival of the bacterium itself offer a tantalizing prospect of novel antimicrobials. They may also reduce the propensity to induce resistance by removing the strong selection pressure imparted by bactericidal or bacteriostatic agents...
2017: PloS One
https://www.readbyqxmd.com/read/28346406/diabetes-reversal-by-inhibition-of-the-low-molecular-weight-tyrosine-phosphatase
#6
Stephanie M Stanford, Alexander E Aleshin, Vida Zhang, Robert J Ardecky, Michael P Hedrick, Jiwen Zou, Santhi R Ganji, Matthew R Bliss, Fusayo Yamamoto, Andrey A Bobkov, Janna Kiselar, Yingge Liu, Gregory W Cadwell, Shilpi Khare, Jinghua Yu, Antonio Barquilla, Thomas D Y Chung, Tomas Mustelin, Simon Schenk, Laurie A Bankston, Robert C Liddington, Anthony B Pinkerton, Nunzio Bottini
Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases...
March 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28346086/a-small-molecule-microarray-approach-for-the-identification-of-e2-enzyme-inhibitors-in-ubiquitin-like-conjugation-pathways
#7
Katherine Zlotkowski, William M Hewitt, Ranu S Sinniah, Joseph E Tropea, Danielle Needle, George T Lountos, Joseph J Barchi, David S Waugh, John S Schneekloth
E2 enzymes in ubiquitin-like conjugation pathways are important, highly challenging pharmacological targets, and despite significant efforts, few noncovalent modulators have been discovered. Small-molecule microarray (SMM)-based screening was employed to identify an inhibitor of the "undruggable" small ubiquitin-like modifier (SUMO) E2 enzyme Ubc9. The inhibitor, a degradation product from a commercial screening collection, was chemically synthesized and evaluated in biochemical, mechanistic, and structure-activity relationship studies...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345904/ligand-selectivity-mechanism-and-conformational-changes-in-guanine-riboswitch-by-molecular-dynamics-simulations-and-free-energy-calculations
#8
Guodong Hu, Aijing Ma, Ji Hua Wang
Riboswitches regulate gene expression through direct and specific interactions with small metabolite molecules. Binding of a ligand to its RNA target is high selectivity and affinity and induces conformational changes of the RNA's secondary and tertiary structure. The structural difference of two purine riboswitches aptamers is caused by only one single mutation, where cytosine 74 in the guanine riboswitch is corresponding to a uracil 74 in adenine riboswitch. Here we employed molecular dynamics (MD) simulation, molecular mechanics Poisson Boltzmann surface area (MM-PBSA) and thermodynamic integration computational methodologies to evaluate the energetic and conformational changes of ligands binding to purine riboswitches...
March 27, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#9
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345158/circular-rnas-in-heart-failure
#10
REVIEW
Yvan Devaux, Esther E Creemers, Reinier A Boon, Stanislas Werfel, Thomas Thum, Stefan Engelhardt, Stefanie Dimmeler, Iain Squire
Cardiovascular disease, and particularly heart failure, is still a serious health care issue for which novel treatments and biomarkers are needed. The RNA family comprises different subgroups, among which the small-sized microRNAs and the larger long non-coding RNAs have shown some potential to aid in moving personalized health care of heart failure patients a step forward. Here, members of the Cardiolinc network review the recent findings suggesting that the less well-known circular RNAs may constitute a novel reservoir of therapeutic targets and biomarkers of heart failure...
March 27, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28345051/aflatoxin-free-transgenic-maize-using-host-induced-gene-silencing
#11
Dhiraj Thakare, Jianwei Zhang, Rod A Wing, Peter J Cotty, Monica A Schmidt
Aflatoxins, toxic secondary metabolites produced by some Aspergillus species, are a universal agricultural economic problem and a critical health issue. Despite decades of control efforts, aflatoxin contamination is responsible for a global loss of millions of tons of crops each year. We show that host-induced gene silencing is an effective method for eliminating this toxin in transgenic maize. We transformed maize plants with a kernel-specific RNA interference (RNAi) gene cassette targeting the aflC gene, which encodes an enzyme in the Aspergillus aflatoxin biosynthetic pathway...
March 2017: Science Advances
https://www.readbyqxmd.com/read/28344889/loss-of-tapasin-in-human-lung-and-colon-cancer-cells-and-escape-from-tumor-associated-antigen-specific-ctl-recognition
#12
Yosuke Shionoya, Takayuki Kanaseki, Sho Miyamoto, Serina Tokita, Ayumi Hongo, Yasuhiro Kikuchi, Vitaly Kochin, Kazue Watanabe, Ryota Horibe, Hiroshi Saijo, Tomohide Tsukahara, Yoshihiko Hirohashi, Hiroki Takahashi, Noriyuki Sato, Toshihiko Torigoe
Cytotoxic T-lymphocytes (CTLs) lyse target cells after recognizing the complexes of peptides and MHC class I molecules (pMHC I) on cell surfaces. Tapasin is an essential component of the peptide-loading complex (PLC) and its absence influences the surface repertoire of MHC class I peptides. In the present study, we assessed tapasin expression in 85 primary tumor lesions of non-small cell lung cancer (NSCLC) patients, demonstrating that tapasin expression positively correlated with patient survival. CD8(+) T-cell infiltration of tumor lesions was synergistically observed with tapasin expression and correlated positively with survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344354/hdac1-3-inhibitor-ms-275-enhances-il10-expression-in-raw264-7-macrophages-and-reduces-cigarette-smoke-induced-airway-inflammation-in-mice
#13
Niek G J Leus, Thea van den Bosch, Petra E van der Wouden, Kim Krist, Maria E Ourailidou, Nikolaos Eleftheriadis, Loes E M Kistemaker, Sophie Bos, Rutger A F Gjaltema, Solomon A Mekonnen, Rainer Bischoff, Reinoud Gosens, Hidde J Haisma, Frank J Dekker
Chronic obstructive pulmonary disease (COPD) constitutes a major health burden. Studying underlying molecular mechanisms could lead to new therapeutic targets. Macrophages are orchestrators of COPD, by releasing pro-inflammatory cytokines. This process relies on transcription factors such as NF-κB, among others. NF-κB is regulated by lysine acetylation; a post-translational modification installed by histone acetyltransferases and removed by histone deacetylases (HDACs). We hypothesized that small molecule HDAC inhibitors (HDACi) targeting class I HDACs members that can regulate NF-κB could attenuate inflammatory responses in COPD via modulation of the NF-κB signaling output...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28343990/impact-of-freeze-thaw-process-on-drug-substance-storage-of-therapeutics
#14
William J Rayfield, Sunitha Kandula, Heera Khan, Nihal Tugcu
The storage of drug substance at subzero temperatures mitigates potential risks associated with liquid storage, such as degradation and shipping stress, making it the best solution for long term storage. However, slower (generally uncontrolled) rates of freezing and thawing of drug substance in conventional large storage containers (> 2L) can lead to greater cryoconcentration (exclusion of solute molecules) resulting in zones of higher protein and excipient concentrations and changes to the desired formulation pH and excipient concentration...
March 23, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28343901/gper-blockers-as-nox-downregulators-a-new-drug-class-to-target-chronic-non-communicable-diseases
#15
Matthias R Meyer, Matthias Barton
Oxidative stress is a hallmark of chronic non-communicable diseases such as arterial hypertension, diabetes, coronary artery disease, and stroke. Cardiovascular diseases are characterized by increased production of reactive oxygen species (ROS) by NAPDH oxidase 1 (Nox1) and additional Nox isoforms among other sources. Activation of the G protein-coupled estrogen receptor (GPER) can mediate multiple salutary effects on the cardiovascular system. However, GPER also has constitutive activity, e.g. in the absence of specific agonists, that was recently shown to promote hypertension and aging-induced tissue damage by enabling Nox1-derived production of ROS...
March 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28343701/toll-like-receptor-8-agonist-nanoparticles-mimic-immunomodulating-effects-of-the-live-bcg-vaccine-and-enhance-neonatal-innate-and-adaptive-immune-responses
#16
David J Dowling, Evan A Scott, Annette Scheid, Ilana Bergelson, Sweta Joshi, Carlo Pietrasanta, Spencer Brightman, Guzman Sanchez-Schmitz, Simon D Van Haren, Jana Ninković, Dina Kats, Cristiana Guiducci, Alexandre de Titta, Daniel K Bonner, Sachiko Hirosue, Melody A Swartz, Jeffrey A Hubbell, Ofer Levy
BACKGROUND: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. OBJECTIVE: Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form...
March 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28343170/mirnas-single-nucleotide-polymorphisms-snps-and-age-related-macular-degeneration-amd
#17
John Paul SanGiovanni, Peter M SanGiovanni, Przemysław Sapieha, Vincent De Guire
Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers for AAMD. The presence of certain single nucleotide polymorphisms (SNPs) may influence the explanatory value of these biomarkers. Here we present findings from an integrated approach used to determine whether AAMD-associated SNPs have the capacity to influence miRNA-mRNA pairing and, if so, to what extent such pairing may be manifested in a discrete AAMD transcriptome...
March 27, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28342876/increased-activity-of-unlinked-zika-virus-ns2b-ns3-protease-compared-to-linked-zika-virus-protease
#18
Benjamin D Kuiper, Kristin Slater, Nicholas Spellmon, Joshua Holcomb, Prasanna Medapureddy, Kendall M Muzzarelli, Zhe Yang, Reuben Ovadia, Franck Amblard, Iulia A Kovari, Raymond F Schinazi, Ladislau C Kovari
Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28341558/biomethane-the-energy-storage-platform-chemical-and-greenhouse-gas-mitigation-target
#19
Zoltán Bagi, Norbert Ács, Tamás Böjti, Balázs Kakuk, Gábor Rákhely, Orsolya Strang, Márk Szuhaj, Roland Wirth, Kornél L Kovács
Results in three areas of anaerobic microbiology in which methane formation and utilization plays central part are reviewed. a.) Bio-methane formation by reduction of carbon dioxide in the power-to-gas process and the various possibilities of improvement of the process is a very intensively studied topic recently. From the numerous potential methods of exploiting methane of biological origin two aspects are discussed in detail. b.) Methane can serve as a platform chemical in various chemical and biochemical synthetic processes...
March 21, 2017: Anaerobe
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#20
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
keyword
keyword
73045
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"