keyword
MENU ▼
Read by QxMD icon Read
search

cancer drug discovery

keyword
https://www.readbyqxmd.com/read/29243581/anticancer-natural-coumarins-as-lead-compounds-for-the-discovery-of-new-drugs
#1
Diana C G A Pinto, Artur M S Silva
Cancer is one of the most serious illnesses of our civilization. The International Agency for Research on Cancer estimated that 14.1 million new cancer cases were diagnosed. Therefore, the cure efficiency of cancer chemotherapy depends not only on how the anticancer drug is delivered to its targets but also on the anticancer drug itself. Among the approved drugs 80% are derived from natural compounds. In this sense, coumarins, natural polyphenols for which anticancer activity has been proved, can be a source or inspire the synthesis of new anticancer agents...
December 14, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29242316/colorectal-cancer-consensus-molecular-subtypes-translated-to-preclinical-models-uncover-potentially-targetable-cancer-cell-dependencies
#2
Anita Sveen, Jarle Bruun, Peter W Eide, Ina A Eilertsen, Lorena Ramirez, Astrid Murumägi, Mariliina A Arjama, Stine A Danielsen, Kushtrim Kryeziu, Elena Elez, Josep Tabernero, Justin Guinney, Hector G Palmer, Arild Nesbakken, Olli Kallioniemi, Rodrigo Dienstmann, Ragnhild A Lothe
PURPOSE: Response to standard oncological treatment is limited in colorectal cancer (CRC). The gene expression-based consensus molecular subtypes (CMS) provide a new paradigm for stratified treatment and drug repurposing, however, drug discovery is currently limited by the lack of translation of CMS to preclinical models. EXPERIMENTAL DESIGN: We analyzed CMS in primary CRCs, cell lines and patient-derived xenografts (PDXs). For classification of preclinical models, we developed an optimized classifier enriched for cancer cell-intrinsic gene expression signals, and performed high-throughput in vitro drug screening (n=459 drugs) to analyze subtype-specific drug sensitivities...
December 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29239784/new-perspectives-for-natural-triterpene-glycosides-as-potential-adjuvants
#3
Marie-Aleth Lacaille-Dubois, Hildebert Wagner
BACKGROUND: Triterpene glycosides are a vast group of secondary metabolites widely distributed in plants including a high number of biologically active compounds. The pharmacological potential is evaluated by using many bioassays particularly in the field of cancerology, immunology, and microbiology. The adjuvant concept is well known for these molecules in vaccines, but there is little preclinical evidence to support this concept in the management of cancer, infections and inflammation...
November 7, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29236213/structural-probing-screening-and-structure-based-drug-repositioning-insights-into-the-identification-of-potential-cox-2-inhibitors-from-selective-coxibs
#4
Uma Devi Bommu, Kranthi Kumar Konidala, Rishika Pamanji, Suneetha Yeguvapalli
The rate-limiting enzyme cyclooxygenase-2 (COX-2) is considered as an insightful prognostic target for non-small cell lung cancer (NSCLC) therapy. Now, administration and prolonged utilization of selective COX-2 inhibitors (COXIBs) towards moderating the NSCLC has been associated with different side effects. In the present study, we focused on the structure-based drug repositioning approaches for predicting therapeutic potential de novo candidates for human COX-2. Due to discrepancies in the eminence of x-ray diffraction structures, creates a big barrier in drug discovery approach...
December 13, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29235148/structural-analysis-of-protein-tyrosine-phosphatase-1b-reveals-potentially-druggable-allosteric-binding-sites
#5
Ammu Prasanna Kumar, Minh N Nguyen, Chandra Verma, Suryani Lukman
Catalytic proteins such as human protein tyrosine phosphatase 1B (PTP1B), with conserved and highly polar active sites, warrant the discovery of druggable non-active sites, such as allosteric sites, and potentially, therapeutic small molecules that can bind to these sites. Catalyzing the dephosphorylation of numerous substrates, PTP1B is physiologically important in intracellular signal transduction pathways in diverse cell types and tissues. Aberrant PTP1B is associated with obesity, diabetes, cancers, and neurodegenerative disorders...
December 13, 2017: Proteins
https://www.readbyqxmd.com/read/29234063/the-sam-sam-interaction-between-ship2-and-the-epha2-receptor-design-and-analysis-of-peptide-inhibitors
#6
Flavia Anna Mercurio, Concetta Di Natale, Luciano Pirone, Roberta Iannitti, Daniela Marasco, Emilia Maria Pedone, Rosanna Palumbo, Marilisa Leone
The lipid phosphatase Ship2 represents a drug discovery target for the treatment of different diseases, including cancer. Its C-terminal sterile alpha motif domain (Ship2-Sam) associates with the Sam domain from the EphA2 receptor (EphA2-Sam). This interaction is expected to mainly induce pro-oncogenic effects in cells therefore, inhibition of the Ship2-Sam/EphA2-Sam complex may represent an innovative route to discover anti-cancer therapeutics. In the present work, we designed and analyzed several peptide sequences encompassing the interaction interface of EphA2-Sam for Ship2-Sam...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233296/protein-protein-and-protein-chromatin-interactions-of-ledgf-p75-as-novel-drug-targets
#7
REVIEW
Jolien Blokken, Jan De Rijck, Frauke Christ, Zeger Debyser
Lens epithelium-derived growth factor p75 (LEDGF/p75), a transcriptional co-activator, plays an important role in tethering protein complexes to the chromatin. Through this tethering function LEDGF/p75 is implicated in a diverse set of human diseases including HIV infection and mixed lineage leukemia, an aggressive form of cancer with poor prognosis. Here we provide an overview of recent progress in resolving protein-protein and protein-chromatin interaction mechanisms of LEDGF/p75. This review will focus on two well-characterized domains, the PWWP domain and the integrase binding domain (IBD)...
June 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/29233023/improving-the-efficacy-safety-balance-of-polypharmacology-in-multi-target-drug-discovery
#8
Balaguru Ravikumar, Tero Aittokallio
Polypharmacology has emerged as an essential paradigm for modern drug discovery process. Multiple lines of evidence suggest that agents capable of modulating multiple targets in a selective manner may offer also improved balance between therapeutic efficacy and safety compared to single-targeted agents. Areas covered: Herein, the authors review the recent progress made in experimental and computational strategies for addressing the critical challenges with rational discovery of selective multi-targeted agents within the context of polypharmacological modelling...
December 12, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29233008/non-polar-compounds-of-persian-gulf-sea-cucumber-holothuria-parva-selectively-induce-toxicity-on-skin-mitochondria-isolated-from-animal-model-of-melanoma
#9
Yalda Arast, Nina Seyed Razi, Melika Nazemi, Enayatollah Seydi, Jalal Pourahmad
PURPOSE: Melanoma is a highly aggressive and deadly cancer with a poor prognosis given its drug resistance. A defect in apoptosis is one of the key mechanisms that contribute to drug resistance in Melonama. An important sea marine animal is the Holothuria parva, also known as the sea cucumber, which has various pharmacological activities. Compounds obtained from sea cucumbers have shown to have anticancer activity through induction of apoptosis singling. MATERIALS AND METHODS: In the present study, selective toxicity and apoptotic effect of three extracts of Holothuria parva (H...
December 12, 2017: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/29232514/discovery-of-novel-selective-acetyl-coa-carboxylase-acc-1-inhibitors
#10
Ryo Mizojiri, Moriteru Asano, Daisuke Tomita, Hiroshi Banno, Noriyuki Nii, Masako Sasaki, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Takeo Moriya, Yoshinori Satomi, Hironobu Maezaki
We initiated our structure-activity relationship (SAR) studies for selective ACC1 inhibitors from 1a as a lead compound. SAR studies of bicyclic scaffolds revealed many potent and selective ACC1 inhibitors represented by 1f, however most of them had physicochemical issues, particularly low aqueous solubility and potent CYP inhibition. To address these two issues and improve the drug-likeness of this chemical series, we converted the bicyclic scaffold into a monocyclic framework. Ultimately, this lead us to discover a novel monocyclic derivative 1q as a selective ACC1 inhibitor, which showed highly potent and selective ACC1 inhibition as well as acceptable solubility and CYP inhibition profiles...
December 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29231137/therapeutic-role-of-harmalol-targeting-nucleic-acids-biophysical-perspective-and-in-vitro-cytotoxicity
#11
Sarita Sarkar, Kakali Bhadra
BACKGROUND: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary biomedical research and drug discovery programs. With time, there is growing interest in search for anti-cancer drugs of plant origin with high efficacy, low toxicity and minimum side effects. Most of the chemotherapeutic agents due to their non-selective nature and dose limiting toxicity, use is often restricted, necessitating search for newer drugs having greater potentiality. OBJECTIVE: The review highlighted the interaction of harmalol with nucleic acids of different motifs as sole target biomolecules and in vitro cytotoxicity of the alkaloid in human cancer cell lines with special emphasis on its apoptotic induction ability...
December 11, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29230203/ibalizumab-targeting-cd4-receptors-an-emerging-molecule-in-hiv-therapy
#12
REVIEW
Simona A Iacob, Diana G Iacob
The HIV infection is responsible for the most devastating global pandemic of the last century. More than 39 million people have died of HIV/AIDS since 1981. The development of the antiretroviral (ARV) treatment begins with the discovery of zidovudine a nucleoside reverse transcriptase inhibitor. This breakthrough was followed by other ARV drug classes and representatives. Presently, HIV treatment employs 27 ARV representatives belonging to five different classes. Despite the proven benefits of ARV treatment and its long-term control of the HIV infection, there is an increasing concern about the numerous adverse effects and resistance to current ARV drugs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29230082/recent-advances-in-adam17-research-a-promising-target-for-cancer-and-inflammation
#13
REVIEW
Marcia L Moss, Dmitry Minond
Since its discovery, ADAM17, also known as TNFα converting enzyme or TACE, is now known to process over 80 different substrates. Many of these substrates are mediators of cancer and inflammation. The field of ADAM metalloproteinases is at a crossroad with many of the new potential therapeutic agents for ADAM17 advancing into the clinic. Researchers have now developed potential drugs for ADAM17 that are selective and do not have the side effects which were seen in earlier chemical entities that targeted this enzyme...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29228590/precision-and-recall-oncology-combining-multiple-gene-mutations-for-improved-identification-of-drug-sensitive-tumours
#14
Stefan Naulaerts, Cuong C Dang, Pedro J Ballester
Cancer drug therapies are only effective in a small proportion of patients. To make things worse, our ability to identify these responsive patients before administering a treatment is generally very limited. The recent arrival of large-scale pharmacogenomic data sets, which measure the sensitivity of molecularly profiled cancer cell lines to a panel of drugs, has boosted research on the discovery of drug sensitivity markers. However, no systematic comparison of widely-used single-gene markers with multi-gene machine-learning markers exploiting genomic data has been so far conducted...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227286/drug-perturbation-based-stratification-of-blood-cancer
#15
Sascha Dietrich, Małgorzata Oleś, Junyan Lu, Leopold Sellner, Simon Anders, Britta Velten, Bian Wu, Jennifer Hüllein, Michelle da Silva Liberio, Tatjana Walther, Lena Wagner, Sophie Rabe, Sonja Ghidelli-Disse, Marcus Bantscheff, Andrzej K Oleś, Mikołaj Słabicki, Andreas Mock, Christopher C Oakes, Shihui Wang, Sina Oppermann, Marina Lukas, Vladislav Kim, Martin Sill, Axel Benner, Anna Jauch, Lesley Ann Sutton, Emma Young, Richard Rosenquist, Xiyang Liu, Alexander Jethwa, Kwang Seok Lee, Joe Lewis, Kerstin Putzker, Christoph Lutz, Davide Rossi, Andriy Mokhir, Thomas Oellerich, Katja Zirlik, Marco Herling, Florence Nguyen-Khac, Christoph Plass, Emma Andersson, Satu Mustjoki, Christof von Kalle, Anthony D Ho, Manfred Hensel, Jan Dürig, Ingo Ringshausen, Marc Zapatka, Wolfgang Huber, Thorsten Zenz
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29226720/memantine-induces-apoptosis-and-inhibits-cell-cycle-progression-in-lncap-prostate-cancer-cells
#16
G Albayrak, E Konac, A U Dikmen, C Y Bilen
Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer's drug...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29225130/on-the-g-protein-coupling-selectivity-of-the-native-a2b-adenosine-receptor
#17
Zhan-Guo Gao, Asuka Inoue, Kenneth A Jacobson
A2B adenosine receptor (A2BAR) activation induces Gs-dependent cyclic AMP accumulation. However, A2BAR G protein-coupling to other signaling events, e.g. ERK1/2 and calcium, is not well documented. We explored Gi, Gq/11 and Gs coupling in 1321N1 astrocytoma, HEK293, and T24 bladder cancer cells endogenously expressing human A2BAR, using NECA or nonnucleoside BAY60-6583 as agonist, selective Gi, Gs and Gq/11 blockers, and CRISPR/Cas9-based Gq- and Gs-null HEK293 cells. In HEK293 cells, A2BAR-mediated ERK1/2 activity occurred via both Gi and Gs, but not Gq/11...
December 7, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29220788/recent-discovery-of-indoleamine-2-3-dioxygenase-1-inhibitors-targeting-cancer-immunotherapy
#18
Tianwei Weng, Xiaqiu Qiu, Jubo Wang, Zhiyu Li, Jinlei Bian
There has been great attention on indoleamine-2,3-dioxygenase 1 (IDO1) around cancer immunotherapy because of its role in enabling cancers to evade the immune system. The most recent spurt of high potent IDO1 inhibitors has been driven by the solution of the increased crystal structures of inhibitors with IDO1. Though the structural information of the active site of IDO1 obtained from the crystals are quite similar, the structures of reported potent inhibitors are quite different. Besides, while thousands of bioactive small molecule inhibitors of IDO1 exist, to date, only five compounds have entered clinical trials...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29218506/in-silico-discovery-of-novel-ligands-for-antimicrobial-lipopeptides-for-computer-aided-drug-design
#19
REVIEW
Satya Eswari Jujjavarapu, Swasti Dhagat
The increase in antibiotic-resistant strains of pathogens has created havoc worldwide. These antibiotic-resistant pathogens require potent drugs for their inhibition. Lipopeptides, which are produced as secondary metabolites by many microorganisms, have the ability to act as potent safe drugs. Lipopeptides are amphiphilic molecules containing a lipid chain bound to the peptide. They exhibit broad-spectrum activities against both bacteria and fungi. Other than their antimicrobial properties, they have displayed anti-cancer properties as well, but their mechanism of action is not understood...
December 7, 2017: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/29218269/blood-based-biomarkers-for-precision-medicine-in-lung-cancer-precision-radiation-therapy
#20
REVIEW
Dirk De Ruysscher, Jianyue Jin, Tim Lautenschlaeger, Jin-Xiong She, Zhongxing Liao, Feng-Ming Spring Kong
Both tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose...
December 2017: Translational Lung Cancer Research
keyword
keyword
2862
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"