journal
MENU ▼
Read by QxMD icon Read
search

Biochemical Pharmacology

journal
https://www.readbyqxmd.com/read/28223017/novel-bcl2-inhibitor-disarib-induces-apoptosis-by-disruption-of-bcl2-bak-interaction
#1
Supriya V Vartak, Divyaanka Iyer, T R Santhoshkumar, Sheetal Sharma, Archita Mishra, Gunaseelan Goldsmith, Mrinal Srivastava, Shikha Srivastava, Subhas S Karki, Avadhesha Surolia, Bibha Choudhary, Sathees C Raghavan
Apoptosis is a highly regulated pathway of programmed cell death relying on the fine balance between pro and antiapoptotic binding partners. Overexpression of the antiapoptotic protein BCL2 in several cancers makes it an ideal target for chemotherapy, with minimum side effects. In one of our previous studies, we designed, synthesized and characterized Disarib, a BCL2-specific small molecule inhibitor. Interestingly, Disarib showed a novel mode of BCL2 inhibition, by predominantly binding to its BH1 domain, as compared to the BH3-specific action of other known BCL2 inhibitors...
February 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28216017/usp7-inhibitor-p5091-inhibits-wnt-signaling-and-colorectal-tumor-growth
#2
An Tao, Gong Yaxiao, Li Xue, Kong Lingmei, Ma Pengcheng, Gong Liang, Zhu Huifang, Yu Chunlei, Liu Jianmei, Zhou Hongyu, Mao Bingyu, Li Yan
Aberrant activation of Wnt/β-catenin signaling is closely associated with the development of various human cancers, especially colorectal cancers (CRC). The ubiquitin proteasome system (UPS) is essential in the regulation of Wnt signaling and inhibitors targeting the UPS could have great potential in CRC therapy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, plays a significant role in neoplastic diseases due to its well-known function of regulating the MDM2-p53 complex. Inspired by our recent study identifying the positive role of USP7 in the Wnt signaling, we report here that USP7 is overexpressed in colorectal carcinoma cell lines and tissues, which is closely related with the poor prognosis...
February 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28216016/the-n-terminal-region-of-organic-anion-transporting-polypeptide-1b3-oatp1b3-plays-an-essential-role-in-regulating-its-plasma-membrane-trafficking
#3
Se-Eun Chun, Nilay Thakkar, Yunseok Oh, Ji Eun Park, Songhee Han, Gongmi Ryoo, Hyunggu Hahn, Sang Hyun Maeng, Young-Ran Lim, Byung Woo Han, Wooin Lee
Organic anion transporting polypeptide 1B3 (OATP1B3) is a major influx transporter mediating the hepatic uptake of various endogenous substrates as well as clinically important drugs such as statins and anticancer drugs. However, molecular mechanisms controlling the membrane trafficking of OATP1B3 have been largely unknown. Several reports recently indicated the presence of a distinct, cancer-type OATP1B3 variant lacking the N-terminal 28 amino acids compared to OATP1B3 expressed in non-malignant hepatocytes...
February 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28214518/potentiating-slc-transporter-activity-emerging-drug-discovery-opportunities
#4
REVIEW
Marie-Laure Rives, Jonathan A Javitch, Alan D Wickenden
Maintaining the integrity of cellular membranes is critical to protecting metabolic activities and genetic information from the environment. Regulation of transport across membranes of essential chemicals, including water, nutrients, hormones and many drugs, is therefore key to cellular homeostasis and physiological processes. The two main transporter superfamilies are ATP-binding cassette (ABC) transporters that primarily function as efflux transporters, and the solute carrier (SLC) transporters. SLC transporters encompass 52 gene families with almost 400 different human transporter genes...
February 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28213273/2-methoxyestradiol-protects-against-ischemia-reperfusion-injury-in-alcoholic-fatty-liver-by-enhancing-sirtuin-1-mediated-autophagy
#5
Hong-Ik Cho, Min-Jong Seo, Sun-Mee Lee
Alcoholic fatty liver (AFL) is susceptible to ischemia/reperfusion (I/R) injury, responding with inflammation and extensive hepatocellular damage. Autophagy maintains cellular homeostasis and regulates inflammation and lipid metabolism. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of estradiol, exhibits antioxidant and anti-inflammatory properties. This study examined the cytoprotective mechanisms of 2-ME2 on hepatic I/R in AFL, focusing on autophagy signaling. C57BL/6 mice were fed an ethanol diet (ED) to induce AFL, or a control diet (CD) for 6 weeks, and then subjected to 60 min of ischemia and 5 h of reperfusion...
February 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28213272/rev-erb-regulation-of-cholesterologenesis
#6
Sadichha Sitaula, Jinsong Zhang, Fernanda Ruiz, Thomas P Burris
REV-ERBα and REV-ERBβ are heme regulated nuclear receptors that are known to regulate metabolic pathways. We previously demonstrated that treatment of mice with synthetic REV-ERB agonists suppressed plasma cholesterol levels and the hepatic levels of the rate limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-Mmethylglutaryl-CoA reductase). Here, we characterize the role of REV-ERB on the cholesterol biosynthetic pathway in greater detail. The REV-ERB agonist SR9009 reduced plasma cholesterol levels in both wild type C57Bl/6 and low density lipoprotein receptor (LDLR) null mice as well as reducing the expression of an array of genes within the cholesterol biosynthetic pathway...
February 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28202288/tiam1-vav2-rac1-axis-a-tug-of-war-between-islet-function-and-dysfunction
#7
REVIEW
Anjaneyulu Kowluru
Glucose-stimulated insulin secretion [GSIS] from the islet β-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Rac1 and Cdc42] have been shown to regulate islet β-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur...
February 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28193451/prolonged-pharmacological-inhibition-of-cathepsin-c-results-in-elimination-of-neutrophil-serine-proteases
#8
Carla Guarino, Yveline Hamon, Cécile Croix, Anne-Sophie Lamort, Sandrine Dallet-Choisy, Sylvain Marchand-Adam, Adam Lesner, Thomas Baranek, Marie-Claude Viaud-Massuard, Conni Lauritzen, John Pedersen, Nathalie Heuzé-Vourc'h, Mustapha Si-Tahar, Erhan Fıratlı, Dieter E Jenne, Francis Gauthier, Marshall S Horwitz, Niels Borregaard, Brice Korkmaz
Cathepsin C (CatC) is a tetrameric cysteine dipeptidyl aminopeptidase that plays a key role in activation of pro-inflammatory serine protease zymogens by removal of an N-terminal pro-dipeptide sequence. Loss of function mutations in the CatC gene are associated with lack of immune cell serine proteases activities and cause Papillon-Lefèvre syndrome (PLS). Also, only very low levels of elastase-like protease zymogens are detected by proteome analysis of neutrophils from PLS patients. Thus, CatC inhibitors represent new alternatives for the treatment of neutrophil protease-driven inflammatory or autoimmune diseases...
February 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28192085/influence-of-peptide-transporter-2-pept2-on-the-distribution-of-cefadroxil-in-mouse-brain-a-microdialysis-study
#9
Xiaomei Chen, Richard F Keep, Yan Liang, Hao-Jie Zhu, Margareta Hammarlund-Udenaes, Yongjun Hu, David E Smith
Peptide transporter 2 (PEPT2) is a high-affinity low-capacity transporter belonging to the proton-coupled oligopeptide transporter family. Although many aspects of PEPT2 structure-function are known, including its localization in choroid plexus and neurons, its regional activity in brain, especially extracellular fluid (ECF), is uncertain. In this study, the pharmacokinetics and regional brain distribution of cefadroxil, a ß-lactam antibiotic and PEPT2 substrate, were investigated in wildtype and Pept2 null mice using in vivo intracerebral microdialysis...
February 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28189726/osteocalcin-and-its-endocrine-functions
#10
REVIEW
Akiko Mizokami, Tomoyo Kawakubo-Yasukochi, Masato Hirata
Bone has traditionally been regarded as a static structural organ that supports movement of the body and protects the internal organs. However, evidence has been accumulated in the past decade showing that bone also functions as an endocrine organ that regulates systemic glucose and energy metabolism. Osteocalcin, an osteoblast-specific secreted protein, acts as a hormone by stimulating insulin production and increasing energy expenditure and insulin sensitivity in target organs. Animal studies have shown that an increase in the circulating concentration of osteocalcin, including via exogenous application of the protein, prevents obesity and glucose intolerance...
February 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28189725/role-of-p-glycoprotein-inhibitors-in-ceramide-based-therapeutics-for-treatment-of-cancer
#11
Samy A F Morad, Traci S Davis, Matthew R MacDougall, Su-Fern Tan, David J Feith, Dhimant H Desai, Shantu G Amin, Mark Kester, Thomas P Loughran, Myles C Cabot
The anticancer properties of ceramide, a sphingolipid with potent tumor-suppressor properties, can be dampened via glycosylation, notably in multidrug resistance wherein ceramide glycosylation is characteristically elevated. Earlier works using the ceramide analog, C6-ceramide, demonstrated that the antiestrogen tamoxifen, a first generation P-glycoprotein (P-gp) inhibitor, blocked C6-ceramide glycosylation and magnified apoptotic responses. The present investigation was undertaken with the goal of discovering non-anti-estrogenic alternatives to tamoxifen that could be employed as adjuvants for improving the efficacy of ceramide-centric therapeutics in treatment of cancer...
February 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28189727/selective-upregulation-of-tnf%C3%AE-expression-in-classically-activated-human-monocyte-derived-macrophages-m1-through-pharmacological-interference-with-v-atpase
#12
Lea Thomas, Zhigang Rao, Jana Gerstmeier, Martin Raasch, Christina Weinigel, Silke Rummler, Dirk Menche, Rolf Müller, Carlo Pergola, Alexander Mosig, Oliver Werz
Pharmacological interference with vacuolar-type H(+)-ATPase (V-ATPase), a proton-translocating enzyme involved in protein transport and pH regulation of cell organelles, is considered a potential strategy for cancer therapy. Macrophages are critically involved in tumor progression and may occur as pro-tumoral M2 phenotype, whereas classically-activated M1 can inhibit tumor development for example by releasing tumor-suppressing molecules, including tumor necrosis factor (TNF)α. Here, we show that targeting V-ATPase by selective inhibitors such as archazolid upregulates the expression and secretion of TNFα in lipopolysaccharide (LPS)- or LPS/interferon (INF)γ-activated M1-like macrophages derived from human blood monocytes...
February 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28188779/inhalation-of-high-concentrations-of-hydrogen-ameliorates-liver-ischemia-reperfusion-injury-through-a2a-receptor-mediated-pi3k-akt-pathway
#13
He Li, Ouyang Chen, Zhouheng Ye, Rongjia Zhang, Huijun Hu, Ning Zhang, Junlong Huang, Wenwu Liu, Xuejun Sun
BACKGROUND AND AIMS: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism. METHODS: To explore the role of the PI3K-Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R+HCH, LY294002 (PI3K inhibitor)+I/R+HCH, and LY+I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1h immediately after surgery...
February 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28159624/phenotypic-screening-of-cannabinoid-receptor-2-ligands-shows-different-sensitivity-to-genotype
#14
Julia M Hillger, Beau le Roy, Zi Wang, Thea Mulder-Krieger, Dorret I Boomsma, P Eline Slagboom, Erik H J Danen, Adriaan P IJzerman, Laura H Heitman
The Cannabinoid Receptor 2 (CB2R) is a G protein-coupled receptor (GPCR) investigated intensively as therapeutic target, however no drug has reached the market yet. We investigated personal differences in CB2R drug responses using a label-free whole-cell assay (xCELLigence) combined with cell lines (Lymphoblastoid Cell Lines) from individuals with varying CB2R genotypes. Responses to agonists, partial agonists and antagonists of various chemical classes were characterized. Endogenous cannabinoids such as 2-AG induced cellular effects vastly different from all synthetic cannabinoids, especially in their time-profile...
January 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28159623/synthetic-biology-era-improving-antibiotic%C3%AC-s-world
#15
REVIEW
Silvia Guzmán-Trampe, Corina D Ceapa, Monserrat Manzo-Ruiz, Sergio Sánchez
The emergence of antibiotic-resistant pathogen microorganisms is a problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules has made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions...
January 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28159622/the-discovery-complex-crystal-structure-and-recognition-mechanism-of-a-novel-natural-pde4-inhibitor-from-selaginella-pulvinata
#16
Yiyou Huang, Xin Liu, Deyan Wu, Guihua Tang, Zengwei Lai, Xuehua Zheng, Yin Sheng, Hai-Bin Luo
Phosphodiesterase-4 (PDE4) is an important drug target for treatment of inflammation-related diseases. Till now, natural PDE4 inhibitors are rare and their co-crystal structures with PDE4 are hardly available. In the present study, selaginpulvilins K and L (1 and 2), two novel fluorene derivatives, were isolated from a traditional Chinese medicine Selaginella pulvinata and exhibited remarkable inhibition against phosphodiesterase-4D (PDE4D) at IC50 11 nM and 90 nM, respectively. Compound 1 also showed a good selectivity across PDE families with the selective fold ranging from 30 to 909...
January 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28159621/potential-biomarkers-and-novel-pharmacological-targets-in-protein-aggregation-related-neurodegenerative-diseases
#17
REVIEW
Chiara Giacomelli, Simona Daniele, Claudia Martini
The aggregation of specific proteins plays a pivotal role in the etiopathogenesis of several neurodegenerative diseases (NDs). β-Amyloid (Aβ) peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated protein tau are the two main neuropathological lesions in Alzheimer's disease. Meanwhile, Parkinson's disease is defined by the presence of intraneuronal inclusions (Lewy bodies), in which α-synuclein (α-syn) has been identified as a major protein component. The current literature provides considerable insights into the mechanisms underlying oligomeric-related neurodegeneration, as well as the relationship between protein aggregation and ND, thus facilitating the development of novel putative biomarkers and/or pharmacological targets...
January 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28131848/dehydroandrographolide-inhibits-oral-cancer-cell-migration-and-invasion-through-nf-%C3%AE%C2%BAb-ap-1-and-sp-1-modulated-matrix-metalloproteinase-2-inhibition
#18
Ming-Ju Hsieh, Jui-Chieh Chen, Wei-En Yang, Su-Yu Chien, Mu-Kuan Chen, Yu-Sheng Lo, Yi-Ting Hsi, Yi-Ching Chuang, Chia-Chieh Lin, Shun-Fa Yang
BACKGROUND AND PURPOSE: Oral cancer is a type of head and neck cancer that is characterized by cancerous tissue growth in the oral cavity. Andrographolide and dehydroandrographolide (DA) are the two principal components of Andrographis paniculata (Burm.f.) Nees and are the main contributors to its therapeutic properties. However, the pharmacological activities of DA remain unclear. EXPERIMENTAL APPROACH: In this study, we used wound closure assay and Boyden chamber assay to determine the effects of DA on oral cancer cell migration and invasion...
January 25, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28131847/inhibition-of-11%C3%AE-hydroxysteroid-dehydrogenase-2-by-the-fungicides-itraconazole-and-posaconazole
#19
Katharina R Beck, Murielle Bächler, Anna Vuorinen, Sandra Wagner, Muhammad Akram, Ulrich Griesser, Veronika Temml, Petra Klusonova, Hideaki Yamaguchi, Daniela Schuster, Alex Odermatt
Impaired 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)-dependent cortisol inactivation can lead to electrolyte dysbalance, hypertension and cardiometabolic disease. Furthermore, placental 11β-HSD2 essentially protects the fetus from high maternal glucocorticoid levels, and its impaired function has been associated with altered fetal growth and a higher risk for cardio-metabolic diseases in later life. Despite its important role, 11β-HSD2 is not included in current off-target screening approaches. To identify potential 11β-HSD inhibitors amongst approved drugs, a pharmacophore model was used for virtual screening, followed by biological assessment of selected hits...
January 25, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28131846/novel-human-bioactive-peptides-identified-in-apolipoprotein-b-evaluation-of-their-therapeutic-potential
#20
Rosa Gaglione, Eliana Dell'Olmo, Andrea Bosso, Marco Chino, Katia Pane, Flora Ascione, Francesco Itri, Sergio Caserta, Angela Amoresano, Angelina Lombardi, Henk P Haagsman, Renata Piccoli, Elio Pizzo, Edwin J A Veldhuizen, Eugenio Notomista, Angela Arciello
Host defence peptides (HDPs) are short, cationic amphipathic peptides that play a key role in the response to infection and inflammation in all complex life forms. It is increasingly emerging that HDPs generally have a modest direct activity against a broad range of microorganisms, and that their anti-infective properties are mainly due to their ability to modulate the immune response. Here, we report the recombinant production and characterization of two novel HDPs identified in human Apolipoprotein B (residues 887-922) by using a bioinformatics method recently developed by our group...
January 25, 2017: Biochemical Pharmacology
journal
journal
21606
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"