keyword
MENU ▼
Read by QxMD icon Read
search

Targetted small molecules

keyword
https://www.readbyqxmd.com/read/28103571/identification-of-aurintricarboxylic-acid-as-a-selective-inhibitor-of-the-tweak-fn14-signaling-pathway-in-glioblastoma-cells
#1
Alison Roos, Harshil D Dhruv, Ian T Mathews, Landon J Inge, Serdar Tuncali, Lauren K Hartman, Donald Chow, Nghia Millard, Holly H Yin, Jean Kloss, Joseph C Loftus, Jeffrey A Winkles, Michael E Berens, Nhan L Tran
The survival of patients diagnosed with glioblastoma (GBM), the most deadly form of brain cancer, is compromised by the proclivity for local invasion into the surrounding normal brain, which prevents complete surgical resection and contributes to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) superfamily, can stimulate glioma cell invasion and survival via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103204/transthoracic-ultrasonography-for-the-immunocompromised-patient-a-pilot-project-that-introduces-transthoracic-ultrasonography-for-the-follow-up-of-hematological-patients-in-romania
#2
Ioana Frinc, Petru Ilies, Florin Zaharie, Delia Dima, Alina Tanase, Ljubomir Petrov, Alexandru Irimie, Cristian Berce, Cosmin Lisencu, Ioana Berindan-Neagoe, Ciprian Tomuleasa, Anca Bojan
In the last decade, there is significant progress in clinical hematology with the discovery of targeted molecules and thus the achievement of both hematologic and molecular responses. Nevertheless, chemotherapy remains the treatment of choice for many types of hematological malignancies. Aggressive chemotherapy leads to immunosuppression, accompanied by a high rate of infections and an increased rate of treatment-related mortality. Invasive fungal infections, as well as more common bacterial and viral infections are frequent in immunocompromised patients as they are difficult to diagnose and treat...
January 18, 2017: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/28103010/a-fluorescent-hsp90-probe-demonstrates-the-unique-association-between-extracellular-hsp90-and-malignancy-in-vivo
#3
Lauren B Crowe, Philip F Hughes, David A Alcorta, Takuya Osada, Aaron P Smith, Juliane Totzke, David R Loiselle, Isaac D Lutz, Madhusudhana Gargesha, Debasish Roy, Jose Roques, David Darr, H Kim Lyerly, Neil L Spector, Timothy Aj Haystead
Extracellular expression of heat shock protein 90 (eHsp90) by tumor cells is correlated with malignancy. Development of small molecule probes that can detect eHsp90 in vivo may therefore have utility in the early detection of malignancy. We synthesized a cell impermeable far-red fluorophore-tagged Hsp90 inhibitor to target eHsp90 in vivo. High resolution confocal and lattice light sheet microscopy show that probe-bound eHsp90 accumulates in punctate structures on the plasma membrane of breast tumor cells and is actively internalized...
January 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28102887/clinical-trial-of-nintedanib-in-patients-with-recurrent-or-metastatic-salivary-gland-cancer-of-the-head-and-neck-a-multicenter-phase-2-study-korean-cancer-study-group-hn14-01
#4
Youjin Kim, Su Jin Lee, Ji Yun Lee, Se-Hoon Lee, Jong-Mu Sun, Keunchil Park, Ho Jung An, Jae Yong Cho, Eun Joo Kang, Ha-Young Lee, Jinsoo Kim, Bhumsuk Keam, Hye Ryun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung-Ju Ahn
BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß)...
January 19, 2017: Cancer
https://www.readbyqxmd.com/read/28102849/berberine-sonodynamic-therapy-induces-autophagy-and-lipid-unloading-in-macrophage
#5
Jiayuan Y Kou, Ying Li, Zhaoyu Y Zhong, Yueqing Q Jiang, Xuesong S Li, Xiaobo B Han, Zhongni N Liu, Ye Tian, Liming M Yang
Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102674/2d-ir-spectroscopy-shows-that-optimised-dna-minor-groove-binding-of-hoechst33258-follows-an-induced-fit-model
#6
Lennart A I Ramakers, Gordon Hithell, John J May, Gregory M Greetham, Paul M Donaldson, Michael Towrie, Anthony W Parker, Glenn A Burley, Neil T Hunt
The induced fit binding model describes a conformational change occurring when a small molecule binds to its biomacromolecular target. The result is enhanced non-covalent interactions between ligand and biomolecule. Induced fit is well-established for small molecule-protein interactions, but its relevance to small molecule-DNA binding is less clear. We investigate the molecular determinants of Hoechst33258 binding to its preferred A-tract sequence relative to a sub-optimal alternating A-T sequence. Results from 2-dimensional infrared spectroscopy, which is sensitive to H-bonding and molecular structure changes, show that Hoechst33258 binding results in loss of minor groove spine of hydration in both sequences, but an additional perturbation of the base propeller twists occurs in the A-tract binding region...
January 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28102325/viral-micrornas-target-a-gene-network-inhibit-stat-activation-and-suppress-interferon-responses
#7
Dhivya Ramalingam, Joseph M Ziegelbauer
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs during latency that are processed to yield ~25 mature microRNAs (miRNAs). We were interested in identifying cellular networks that were targeted by KSHV-miRNAs and employed network building strategies using validated KSHV miRNA targets. Here, we report the identification of a gene network centering on the transcription factor- signal transducer and activator of transcription 3 (STAT3) that is targeted by KSHV miRNAs. KSHV miRNAs suppressed STAT3 and STAT5 activation and inhibited STAT3-dependent reporter activation upon IL6-treatment...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#8
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101643/polymorphisms-in-genes-encoding-mir-155-and-mir-146a-are-associated-with-protection-to-type-1-diabetes-mellitus
#9
Taís S Assmann, Guilherme C K Duarte, Letícia A Brondani, Pedro H O de Freitas, Égina M Martins, Luís H Canani, Daisy Crispim
AIMS: Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation...
January 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28101541/inner-salt-shaped-small-molecular-photosensitizer-with-extremely-enhanced-two-photon-absorption-for-mitochondrial-targeted-photodynamic-therapy
#10
Wenbo Hu, Tingchao He, Rongcui Jiang, Jun Yin, Lin Li, Xiaomei Lu, Hui Zhao, Lei Zhang, Ling Huang, Handong Sun, Wei Huang, Quli Fan
Herein, we experimentally and theoretically demonstrate an unprecedentedly enhanced two-photon absorption in a small organic molecule by a simple introduction of an inner salt-shaped structure. Moreover, such an inner salt-shaped small molecule also exhibits superior singlet oxygen quantum yield and fascinating structure-inherent mitochondrial-targeting ability for highly efficient two-photon photodynamic therapy via a mitochondrial apoptosis pathway.
January 19, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28100780/a-novel-microrna-located-in-trkc-gene-regulates-wnt-signaling-pathway-and-is-differentially-expressed-in-colorectal-cancer-specimens
#11
Sadat Dokanehiifard, Atena Yasari, Hadi Najafi, Meisam Jafarzadeh, Maryam Nikkhah, Seyed Javad Mowla, Bahram M Soltani
Tropomyosin receptor kinase C (TrkC) is involved in cell survival, apoptosis, differentiation and tumorigenesis. TrkC diverse functions might be attributed to the hypothetical non-coding RNAs, embedded within the gene. Using bioinformatics approaches, a novel miRNA named TrkC-miR2 was predicted within TrkC gene, capable of regulating Wnt pathway. For experimental verification of this miRNA, predicted TrkC-premir2 sequence was overexpressed in SW480 cells, which led to the detection of two mature TrkC-miR2 isomiRs, and their endogenous forms were detected in human cell lines as well...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100396/small-molecules-remain-on-target-for-c-myc
#12
Linchong Sun, Ping Gao
Targeting the transcription factor c-Myc via one of its coactivator proteins is a promising strategy for cancer therapy.
January 19, 2017: ELife
https://www.readbyqxmd.com/read/28100269/a-spleen-tyrosine-kinase-inhibitor-attenuates-the-proliferation-and-migration-of-vascular-smooth-muscle-cells
#13
Hyang-Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Eunhyun Choi, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang
BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay...
January 18, 2017: Biological Research
https://www.readbyqxmd.com/read/28100240/reactivation-of-dormant-anti-tumor-immunity-a-clinical-perspective-of-therapeutic-immune-checkpoint-modulation
#14
REVIEW
Richard Greil, Evelyn Hutterer, Tanja Nicole Hartmann, Lisa Pleyer
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28099841/targeted-inhibition-of-egfr-and-glutaminase-induces-metabolic-crisis-in-egfr-mutant-lung-cancer
#15
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Clara Magyar, Daniel Braas, Thomas Graeber, Nicholas J Jackson, Johannes Czernin, Ethan Emberley, Matthew Gross, Julie Janes, Andy Mackinnon, Alison Pan, Mirna Rodriguez, Melissa Works, Winter Zhang, Francesco Parlati, Susan Demo, Edward Garon, Kostyantyn Krysan, Tonya C Walser, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28098972/hepta-mutant-staphylococcus-aureus-sortase-a-srta7m-as-a-tool-for-in-vivo-protein-labeling-in-caenorhabditis-elegans
#16
Qin Wu, Hidde L Ploegh, Matthias C Truttmann
In vivo protein ligation is of emerging interest as a means of endowing proteins with new properties in a controlled fashion. Tools to site-specifically and covalently modify proteins with small molecules, peptides, or other proteins in living cells are few and far between. Here, we describe the development of a Staphylococcus aureus sortase (SrtA)-based protein ligation approach for site-specific conjugation of fluorescent dyes and ubiquitin (Ub) to modify proteins in Caenorhabditis elegans. Hepta-mutant SrtA (SrtA7m) expressed in C...
January 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28098453/surface-engineered-multifunctional-eu-gd2o3-nanoplates-for-targeted-and-ph-responsive-drug-delivery-and-imaging-applications
#17
Arindam Saha, Subas Chandra Mohanta, Kashmiri Deka, Pritam Deb, Parukuttyamma Sujatha Devi
In this paper, we report the synthesis of surface-engineered multifunctional Eu:Gd2O3 triangular nanoplates with small size and uniform shape via a high-temperature solvothermal technique. Surface engineering has been performed by a one-step polyacrylate coating, followed by controlled conjugation chemistry. This creates the desired number of surface functional groups that can be used to attach folic acid as a targeting ligand on the nanoparticle surface. To specifically deliver the drug molecules in the nucleus, the folate density on the nanoparticle surface has been kept low...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28098291/investigation-into-the-bioavailability-of-milk-protein-derived-peptides-with-dipeptidyl-peptidase-iv-inhibitory-activity-using-caco-2-cell-monolayers
#18
Isabelle M E Lacroix, Xiu-Min Chen, David D Kitts, Eunice C Y Li-Chan
In recent years, peptides derived from a variety of dietary proteins have been reported to exhibit inhibitory activity against the dipeptidyl-peptidase IV (DPP-IV) enzyme, a target in the management of type 2 diabetes. While much attention has been given to the production and identification of peptides with DPP-IV inhibitory activity from food proteins, particularly dairy proteins, little is known on the bioavailability of these molecules. In this study, the stability and transport of five previously identified milk-derived peptides (LKPTPEGDL, LPYPY, IPIQY, IPI and WR) and a whey protein isolate (WPI) digest with DPP-IV-inhibitory activity were investigated using Caco-2 cell monolayers as a model system for human intestinal absorption...
January 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28098154/structural-basis-of-ligand-interaction-with-atypical-chemokine-receptor-3
#19
Martin Gustavsson, Liwen Wang, Noortje van Gils, Bryan S Stephens, Penglie Zhang, Thomas J Schall, Sichun Yang, Ruben Abagyan, Mark R Chance, Irina Kufareva, Tracy M Handel
Chemokines drive cell migration through their interactions with seven-transmembrane (7TM) chemokine receptors on cell surfaces. The atypical chemokine receptor 3 (ACKR3) binds chemokines CXCL11 and CXCL12 and signals exclusively through β-arrestin-mediated pathways, without activating canonical G-protein signalling. This receptor is upregulated in numerous cancers making it a potential drug target. Here we collected over 100 distinct structural probes from radiolytic footprinting, disulfide trapping, and mutagenesis to map the structures of ACKR3:CXCL12 and ACKR3:small-molecule complexes, including dynamic regions that proved unresolvable by X-ray crystallography in homologous receptors...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28097652/mdm4-is-a-rational-target-for-treating-breast-cancers-with-mutant-p53
#20
Panimaya Jeffreena Miranda, Daniel Buckley, Dinesh Raghu, Jia-Min B Pang, Elena A Takano, Reshma Vijayakumaran, Amina F A S Teunisse, Atara Posner, Tahlia Procter, Marco J Herold, Cristina Gamell, Jean-Christophe Marine, Stephen B Fox, Aart Jochemsen, Sue Haupt, Ygal Haupt
Mutation of the key tumour suppressor p53 defines a transition in the progression toward aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, p53 mutation frequency exceeds 50% in Triple Negative BC (TNBC). Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells...
January 18, 2017: Journal of Pathology
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"