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Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

0 | Aug 19 2019

Chen YN et al. demonstrated that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. [Read the Full Post]

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

12 | Aug 09 2019

Chen YN et al. demonstrated that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. [Read the Full Post]

Treatment of γ-Hydroxybutyric Acid (GHB) and γ-Butyrolactone (GBL) Overdose with Two Potent Monocarboxylate Transporter 1 (MCT1) Inhibitors, AZD3965 and AR-C155858

102 | Apr 29 2019

Follman KE et al. indicated that inhibition of MCT1 is an effective treatment for GHB/GBL overdose. SIGNIFICANCE STATEMENT: This research demonstrates the efficacy of a potent MCT1 inhibitor, AZD2965, as a treatment for GHB overdose. AZD3965 was shown to reduce the brain exposure of GHB, and therefore reduce the toxic impact of GHB. This compound may have the potential to be developed to treat GHB overdose clinically. [Read the Full Post]

MicroRNA-24-1 suppresses mouse hepatoma cell invasion and metastasis via directly targeting O-GlcNAc transferase

0 | Jan 14 2019

Liu Y et al. suggested that as a tumor suppressor, miR-24-1 may regulate mouse hepatocarcinoma cells migration and invasion, at least partially through targeting OGT, which could regulate the O-GlcNAcylation and the stability of this oncoprotein c-Myc. This may give insight into a novel mechanism and therapy of tumor lymphatic metastasis. [Read the Full Post]

MicroRNA-24-1 suppresses mouse hepatoma cell invasion and metastasis via directly targeting O-GlcNAc transferase

145 | Jan 14 2019

Liu Y et al. suggested that as a tumor suppressor, miR-24-1 may regulate mouse hepatocarcinoma cells migration and invasion, at least partially through targeting OGT, which could regulate the O-GlcNAcylation and the stability of this oncoprotein c-Myc. This may give insight into a novel mechanism and therapy of tumor lymphatic metastasis. [Read the Full Post]

Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner

0 | Dec 25 2018

Vinholt PJ et al. indicated that dabigatran exclusively inhibits thrombin-induced platelet activation and aggregation with a dose-dependent response. Platelet stimulation with other agonists was not affected by dabigatran. [Read the Full Post]

MicroRNA-24-1 suppresses mouse hepatoma cell invasion and metastasis via directly targeting O-GlcNAc transferase

90 | Dec 17 2018

Liu Y et al. suggested that as a tumor suppressor, miR-24-1 may regulate mouse hepatocarcinoma cells migration and invasion, at least partially through targeting OGT, which could regulate the O-GlcNAcylation and the stability of this oncoprotein c-Myc. This may give insight into a novel mechanism and therapy of tumor lymphatic metastasis. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

295 | Dec 17 2018

Wang J et al. demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model. One possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Dec 09 2018

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

0 | Dec 07 2018

Lee S et al. revealed that CCN1-GFs treated with sclareol showed decreased levels of UVB-induced CCN1 expression. Sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. [Read the Full Post]

Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer

141 | Nov 05 2018

Zhang F et al. provided new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis. [Read the Full Post]

Dichloroacetate induces regulatory T-cell differentiation and suppresses Th17-cell differentiation by pyruvate dehydrogenase kinase-independent mechanism

262 | Sep 12 2018

Makita N et al. indicated that Dichloroacetate possesses Treg induction and Th17 suppression, which is independent of PDHK and dependent on ROS production. [Read the Full Post]

Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells

280 | Sep 07 2018

Gu HR et al. found that the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future. [Read the Full Post]

Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenström Macroglobulinemia

696 | Aug 17 2018

Kuiatse I et al. supported the translation of approaches targeting Syk with fostamatinib to the clinic for patients with relapsed and possibly even newly diagnosed WMG. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Jul 14 2018

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. [Read the Full Post]

Role and mechanism of PTEN in adiponectin-induced osteogenesis in human bone marrow mesenchymal stem cells

325 | Jul 11 2018

Liu X et al. suggested that APN enhanced osteogenic differentiation of hBMSCs in vitro partially by inhibiting PTEN expression. APN could be a therapeutic agent in tissue regeneration engineering and bone regeneration by inhibiting PTEN expression and then promoting the osteogenic differentiation of hBMSCs. [Read the Full Post]

Hepatitis B Virus Middle Protein Enhances IL-6 Production via p38 MAPK/NF-κB Pathways in an ER Stress-Dependent Manner

301 | Jun 05 2018

Li YX et al. provided a possibility that MHBs could be involved in liver disease progression. [Read the Full Post]

WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma

400 | Jun 02 2018

Wen J et al. suggested an important cross-talk between SHH and WIP1 pathways that accelerates tumorigenesis and supports WIP1 inhibition as a potential treatment strategy for MB. [Read the Full Post]

Calcineurin complex isolated from T-cell acute lymphoblastic leukemia (T-ALL) cells identifies new signaling pathways including mTOR/AKT/S6K whose inhibition synergize with calcineurin inhibition to promote T-ALL cell death

563 | May 26 2018

Tosello V et al. identified AKT inhibition as a novel promising drug combination to potentiate the pro-apoptotic effects of Cn inhibitors. [Read the Full Post]

Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells

0 | May 26 2018

Song Y et al. revealed that accumulation of AGEs in NP tissue may initiate inflammation-related degeneration of the intervertebral disc via activation of the NLRP3 inflammasome. [Read the Full Post]

Knockdown of eIF4E suppresses cell proliferation, invasion and enhances cisplatin cytotoxicity in human ovarian cancer cells

311 | May 25 2018

Wan J, et al. found that knockdown eIF4E gene can be used as a potential therapeutic target for the treatment of human ovarian cancer. [Read the Full Post]

Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model

0 | May 24 2018

Zhang Y et al. indicated that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. [Read the Full Post]

The neuroprotection of Sinomenine against ischemic stroke in mice by suppressing NLRP3 inflammasome via AMPK signaling

322 | Apr 12 2018

Qiu J et al. demonstrated that SINO exerts a neuroprotective effect in ischemic stroke by inhibiting NLRP3 inflammasomes via the AMPK pathway, which also provides evidence of a novel treatment for clinical stroke therapy. [Read the Full Post]

Induction of p53-independent apoptosis by ectopic expression of HOXA5 in human liposarcomas

318 | Apr 04 2018

Lee DH et al. demonstrated for the first time that the downregulation of HOXA5 in LPS cells, partly by overexpression of miR-26a-2 in DDLPS, confers LPS cells resistance to apoptotic death. [Read the Full Post]

Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures

443 | Mar 21 2018

Fraveto A et al. identified a dual PI3-kinase/mTOR inhibitor that both in vitro and in vivo, exerts dramatic antiproliferative effects against both mucin- and mixed-IHCCA. [Read the Full Post]

Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner

470 | Feb 18 2018

Vinholt PJ et al. found dabigatran exclusively inhibits thrombin-induced platelet activation and aggregation with a dose-dependent response. [Read the Full Post]

tRNA modification profiles of the fast-proliferating cancer cells

0 | Oct 06 2017

Dong C et al. indicated that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. [Read the Full Post]

The serum and glucocorticoid-regulated protein kinases (SGK) stimulate bovine herpesvirus 1 and herpes simplex virus 1 productive infection

0 | Jul 29 2017

Kook I et al. suggest SGK may stimulate viral replication following stressful stimuli. [Read the Full Post]

Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate

0 | Jun 06 2017

Hoffman M et al. found that a cell-based model reflects the effects on thrombin generation of clinically relevant levels of FVIIa and PCC in the presence of dabigatran. [Read the Full Post]

Endoplasmic reticulum stress in mouse decidua during early pregnancy

0 | Apr 01 2017

Xiao Wei Gu et al showed that ER stress induces DNA damage and polyploidization in stromal cells. In conclusion, our data suggest that the GRP78/Ire1/Xbp1 signaling pathway of ER stress-UPR is activated and involved in mouse decidualization. [Read the Full Post]

Reversal of Dabigatran Effects in Models of Thrombin Generation and Hemostasis by Factor VIIa and Prothrombin Complex Concentrate

0 | Mar 25 2017

Hoffman M et al suggested that a cell-based model reflects the effects on thrombin generation of clinically relevant levels of FVIIa and PCC in the presence of dabigatran. Enhancing the rate of thrombin generation and peak thrombin level appear to correlate best with hemostasis in vivo. The ineffectiveness of FVIIa at supratherapeutic dabigatran levels may explain conflicting reports of its efficacy in dabigatran reversal. [Read the Full Post]

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

844 | Mar 24 2017

Guo Y et al. suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance. [Read the Full Post]

Autophagy dysfunction upregulates beta-amyloid peptides via enhancing the activity of γ-secretase complex

1103 | Mar 08 2017

Cai Z et al. found that autophagy inhibitor may activate γ-secretase and promote Aβ production and accumulation, but has no influence on Aβ clearance. [Read the Full Post]

Antiviral activity of micafungin against enterovirus 71

0 | Mar 04 2017

Kim C et al. revealed a new indication of micafungin as an effective inhibitor of EV71, which is the first case reporting antiviral activity of micafungin, an antifungal drug. [Read the Full Post]

Solitary inhibition of the breast cancer resistance protein (BCRP) efflux transporter results in a clinically significant drug-drug interaction with rosuvastatin by causing up to a two-fold increase in statin exposure

1785 | Feb 25 2017

Elsby R, et al.'s result shows that solitary inhibition of the intestinal BCRP transporter can result in clinically significant DDIs with rosuvastatin, causing up to a maximum 2-fold increase in exposure, which may warrant statin dose adjustment in clinical practice [Read the Full Post]

Metformin regulates differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms

1000 | Feb 23 2017

Li WD, et al.'s results here showed that metformin could regulate the differentiation of EPCs. Autophagy related pathway and AMPK-eNOS-NO pathway were involved in the mechanisms. [Read the Full Post]

Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent

0 | Feb 22 2017

Thangamani S, et al.'s study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections. [Read the Full Post]

Repurposing celecoxib as a topical antimicrobial agent

0 | Feb 21 2017

Thangamani S, et al.'s results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections. [Read the Full Post]

Anidulafungin-Induced Suicidal Erythrocyte Death

0 | Feb 18 2017

Anidulafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to Ca2+ entry and activation of p38 kinase. [Read the Full Post]

Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate

1924 | Jan 30 2017

The ineffectiveness of FVIIa at supratherapeutic dabigatran levels may explain conflicting reports of its efficacy in dabigatran reversal. [Read the Full Post]

Antiviral activity of micafungin against enterovirus 71

0 | Jan 21 2017

The research of Kim C et al. revealed a new indication of micafungin as an effective inhibitor of EV71, which is the first case reporting antiviral activity of micafungin, an antifungal drug. [Read the Full Post]

Solitary Inhibition of the Breast Cancer Resistance Protein Efflux Transporter Results in a Clinically Significant Drug-Drug Interaction with Rosuvastatin by Causing up to a 2-Fold Increase in Statin Exposure

956 | Jan 13 2017

Elsby R et al. found that solitary inhibition of the intestinal BCRP transporter can result in clinically significant DDIs with rosuvastatin, causing up to a maximum 2-fold increase in exposure, which may warrant statin dose adjustment in clinical practice. [Read the Full Post]

Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent

1148 | Jan 12 2017

The study of Thangamani S et al. lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections. [Read the Full Post]

Metformin regulates differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms

864 | Jan 12 2017

Li WD, et al.'s results here showed that metformin could regulate the differentiation of EPCs. Autophagy related pathway and AMPK-eNOS-NO pathway were involved in the mechanisms [Read the Full Post]

Repurposing celecoxib as a topical antimicrobial agent

1663 | Jan 11 2017

Thangamani S, et al.'s results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections. [Read the Full Post]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

1049 | Dec 26 2016

Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]

The serum and glucocorticoid-regulated protein kinases (SGK) stimulate bovine herpesvirus 1 and herpes simplex virus 1 productive infection

1111 | Dec 13 2016

Kook I et al.’s studies suggested that SGK may stimulate viral replication following stressful stimuli. [Read the Full Post]

Antiviral activity of micafungin against enterovirus 71

2460 | Dec 10 2016

The research of Kim C et al. revealed a new indication of micafungin as an effective inhibitor of EV71, which is the first case reporting antiviral activity of micafungin, an antifungal drug. [Read the Full Post]

Cannabinoid receptor-2 stimulation suppresses neuroinflammation by regulating microglial M1/M2 polarization through the cAMP/PKA pathway in an experimental GMH rat model

1426 | Nov 23 2016

The results of Tao Y et al. will help to further understand the mechanisms that underlie neuroprotection by CB2R in GMH and promote clinical translational research for CB2R agonists. [Read the Full Post]

tRNA modification profiles of the fast-proliferating cancer cells

1660 | Nov 22 2016

Dong C et al.'s results indicated that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. [Read the Full Post]

Anidulafungin-Induced Suicidal Erythrocyte Death

2286 | Nov 09 2016

Anidulafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to Ca2+ entry and activation of p38 kinase. [Read the Full Post]

Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II-mediated hypertension

1650 | Oct 26 2016

Porpino SK et al. suggested that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase. [Read the Full Post]

The effect of hyperlipidemia on the pharmacokinetics, hepatic and pulmonary uptake of posaconazole in rat

1419 | Oct 18 2016

Khalil HA et al. found that poloxamer induced lipoprotein level elevation caused alterations in the PSZ pharmacokinetics and decreased its hepatic and pulmonary uptake. [Read the Full Post]

Endoplasmic reticulum stress in mouse decidua during early pregnancy

1332 | Sep 06 2016

Xiao Wei Gu, et al. suggested that the GRP78/Ire1/Xbp1 signaling pathway of ER stress-UPR is activated and involved in mouse decidualization. [Read the Full Post]

The role of heat shock protein beta-1 in erastin-induced ferroptosis

3596 | Mar 09 2015

Sun et al. found heat shock protein beta-1 (HSPB1) as a key negative mediator of ferroptotic cancer cell death. [Read the Full Post]

STIM2 promotes store-operated calcium entry via enhancing recruitment of STIM1 to the ER-PM junctions

1906 | Jan 26 2015

Ong et al. found STIM2 promotes STIM1 recruitment in endoplasmic reticulum- plasma membrane junctions at low stimulus intensities, results in the enhancement of store-operated calcium entry. [Read the Full Post]

Snail also acts as a transactivator for the expression of tumor-associated cytokines

5505 | Jan 16 2015

Hsu et al. demonstrated the underlying mechanism of Snail-mediated target gene transactivation, and also identified several target genes. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

7829 | Jan 06 2015

Haskins et al. found ERBB4 activated the transcriptional coactivator YAP by binding to its ligand neuregulin 1 (NRG1), to regulate gene expression of cancer cells. [Read the Full Post]

Resvertrol targets a human tRNA synthetase for activation of NAD+-dependent PARP1

4369 | Jan 05 2015

Mathew Sajish and Paul Schimmel found resvertrol interacts with tyrosyl transfer-RNA (tRNA) synthetase (TyrRS), which translocates to the nucleus in response to stress, to initiating its effect in nuclear. [Read the Full Post]

Retinoic acid and Wnt signaling are key regulators in development of hematopoietic stem cells

5282 | Dec 02 2014

Chanda et al. identified retinoic acid (RA) and Wnt signaling pathways as key mediators of HSC development. [Read the Full Post]

Docetaxel is a clinically well established anti mitotic chemotherapy medication

2167 | Dec 25 2013

Docetaxel, an analog of taxol, is an inhibitor of depolymerisation of microtubules through binding to stabilized microtubules. [Read the Full Post]

Salubrinal is a drug which acts as a specific inhibitor of eIF2a

2807 | Dec 11 2013

Salubrinal is a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit α (eIF2α). [Read the Full Post]

AM803 is under development as an oral controller for the treatment

2249 | Oct 25 2013

GSK2190915 (AM803), a potent FLAP inhibitor, prevents the synthesis of leukotrienes and 5-oxo-ETE, with IC50 of 76 nM for inhibition of LTB4 in human blood, provides treatment for asthma. [Read the Full Post]

LY2886721 is used to treat Alzheimers Disease in preclinical experiments

2309 | Aug 23 2013

LY2886721 is an BACE inhibitor used for the treatment of Alzheimer's Disease. [Read the Full Post]

AMG517 is a potent and selective transient receptor potential TRPV1 antagonist

2213 | Jul 31 2013

Oral administration of AMG 517 produces a dose-dependent increase in plasma concentrations, it also produces a dose-dependent decrease in the number of flinches induced by capsaicin treatment. [Read the Full Post]

HIGH THROUGHPUT SCREENING HELPING THE DRUG DISCOVERY

3422 | Oct 14 2012

HIGH THROUGHPUT SCREENING: INTRODUCTION: In pharmaceutical industries different techniques are important and used for the novel drug discovery. Among these techniques the most effective one in this area is high throughput chemical screening. It is also named as HTS assays or high throughput assays which are being used for the biological, pharmacological assessment or the assessment of biochemical activities of a large number of drugs by the help of the latest automatic technology. Such technology is not only helpful in discovery of appropriate receptors, enzymes, ligands for different ion channels and the other pharmacologically important targets but also used in the extensive studies of various desired biochemical or cellular pathways by the aid of unknown and novel chemical agents. Regarding this an important example is of the screening of kinase inhibitor library for screening that is much easier than various other traditional methodologies. Reviews of high throughput screening are an efficient source of acknowledging the importance of HTS. These reviews reveal the speed and accuracy of high throughput screening in the pharmaceutical industries in improving the scientific approaches and business structures. [Read the Full Post]

KINASE INHIBITORS IN CANCER THERAPY

3180 | Oct 10 2012

KINASES IN CELL SIGNALLING: Kinases can rightly be called as the gateways of the cells due to their role in signal transduction in the cell. They function by activating or stimulating the critical pathway by phosphorylating the protein molecules. After getting stimulated enzymes allow the cells to perform some specific functions necessary for its proliferation, survival and growth etc. kinases are of many types which are Receptor tyrosine kinases (RTKs), non-receptor tyrosine kinases (NRTKs) and serine/threonine kinases. Mixed kinases and histidine kinases are also some of the examples of kinases. Basically kinases themselves get activated by a signaling molecule like a ligand from the extracellular environment or some other kinases and further activate subsequent molecule by phosphorylating or dephosphorylating them. Aurora kinase is an important example of kinase enzymes. Different types of agonist and antagonist molecules are used to study and unveil different functions of kinases in the cells. Kinase inhibitor is one of the examples of outcomes of such research on kinases and their inhibition. Different types of kinase assays are also there to study and analyze some specific kinds of kinases. [Read the Full Post]

DRUG DISCOVERY AND COMPOUND LIBRARIES

3407 | Sep 29 2012

INTRODUCTION: A large number of compounds stored for the purpose of discovering something beneficial and more efficient we are looking for is known as compound library screening. A compound library is constructed for the purpose of drug discovery and is screened for the best drug by high through put screening techniques of recent era. Compounds included in the library are fully organized by a specific database system containing information about the compounds and their related properties like purity, chemical structure, physical, chemical and pharmacological properties, and the preparation of that compound . Lots of libraries of different compounds are available commercially that contain different common or unique type of biochemical compounds. Description of these compounds and complete information is available in a file named research chemical library which can be bought from the suppliers of relevant compound libraries. [Read the Full Post]

COMPOUND LIBRARIES AND THEIR USAGE

3120 | Sep 25 2012

COMPOUND LIBRARY: A compound library is like a library of books where different titles and different content is available at a single place. Storage of compounds and their related data makes a compound library where different compounds are collected and arranged for some specific purposes. The compound screening of the library are placed, maintained and stored in a very scientific way. Drug discovery is one of the major purposes of making compound libraries. Recent technologies to organize and design chemical compound library have made the process of drug discovery a more interesting and attractive research area for the scientists and remarkable successes have been seen after the fast growing technologies have made its research easier. The most important thing after construction of compound library is its screening that is looking for the best suited compound relevant to question we are seeking the answer for and the compound that is biologically more active. [Read the Full Post]

KINASES INHIBITION FOR CANCER THERAPY

2973 | Sep 24 2012

SIGNALING THROUGH KINASES: Kinase enzymes are the protein phosphorylating enzymes which act as gateways for the transmission of metabolic signals from the extracellular to intracellular environment of the cell. Kinases stimulate the cells to perform the processes which are necessary for the cell survival, proliferation and cell growth etc. Many types of kinase enzymes exist in the cells like serine/threonine kinases, receptor tyrosine kinases and non-receptor tyrosine kinases, Histidine kinases and the mixed kinases. Basic mechanism of action of kinase proteins is to aquire activated state by some sort of signaling compound that can be a special ligand or some other kind of kinase and send the stimulus to the subsequent molecule in form of its dephosphorylation or phosphorylation. One of the important examples of such kinases is p38 MAP kinase. [Read the Full Post]

HIGH THROUGHPUT SCREENING AND DRUG DISCOVERIES

0 | Sep 19 2012

INTRODUCTION: Various techniques are important in pharmaceutical industries which are used for the discovery of novel drugs, one of the most effective technique in this field is high throughput screening. This is also known as high throughput assay or HTS assays which are utilized for the assessment of pharmacological, biological or biochemical activities of a huge number of drugs by the aid of latest and automatic technology. This technique is not only useful for the discovery of appropriate ligands for ion channels, receptors, enzymes and other important pharmaceutical targets but also used for extensive studies of biochemical or desired cellular pathways by the help of novel and unknown chemical molecules. In this regard an example is of screening of kinase inhibitor library which is quiet easier than many traditional methodologies. High throughput screening reviews are an efficient source of understanding the importance of HTS screening, these reviews describe the accuracy and speed of the HTS screening in pharmaceutical industries in terms of business improvement structures and scientific approaches. [Read the Full Post]

KINASE INHIBITORS AND CANCER THERAPY

2905 | Aug 23 2012

KINASE-DOWNSTREAM SIGNALING: Kinases act as windows for cells to the outer world, these enzymes are triggered by the signals coming from other cells, stimuli from the environment and as a result these kinases carry out phosphorylaiton of various molecules to transmit downstream signals. There are many types of kinase enzymes such as pim kinase and out of these most common are protein kinases. These protein kinases can also be further subdivided into various categories like receptor tyrosine kinase enzyme, threonine/serine protein kinases, mixed kinases and histidine protein kinases. Many of the kinase agonists and kinase antagonists have been employed for the understanding of multiple cellular pathways during research under physiological environment. Reviews on kinase inhibitors can prove the importance of these small compounds. There are various kinase assays are available which can be used for the activity assessment of a kinase enzyme in a given state. [Read the Full Post]

COMPOUND LIBRARY AND ITS BENIFITS

3013 | Aug 21 2012

THE BASIC CONCEPT OF COMPOUND LIBRARY: The collection of data about different compounds at a place where all these compounds can be analyzed by the good worth of their storage is known as a compound library. Hence compound library is basically a collection or arrangement of different compounds. The maintenance, storage and placing of these screening compounds is actually a proper scientific way. The development of different new and emerging technologies in designing and managing of a chemical screening library has brought very remarkable success and changes in the procedure of drug discovery and these new changes have a great and positive impact on the ongoing research on drug discovery [1]. The most determining and crucial step in this procedure of compound library screening is the selection of biologically relevant and useful compounds and molecules that is usually guided by some experts of this area who would must devise some detailed protocols and schemes to make this process of selection faster, more efficient and better than ever in generating a resourceful research chemicals library. State-of-the-art methodologies that include both the fragment-based library designing and the structure-based small molecule library designing procedure is supported by the latest and efficient software tools which ensure a promising implementation of a small molecule drug screening library. [Read the Full Post]

COMPOUND LIBRARIES AND THEIR ADVANTAGES

3737 | Aug 19 2012

COMPOUND LIBRARIES: INTRODUCTION AND FUNCTIONS A fair to a big group of the stored compounds which can be used for industrial manufacturing of drugs or the high-throughput screening assay based drug discovery, is defined as a compound library. This collection or group of compounds is supported by the specific kind of database that contains the relevant information and knowledge about the included compounds and that information includes the compound’s purity, preparation, chemical structure, chemical, physical and pharmacological properties [1]. A lot of compound libraries are commercially available and they might contain a mixture of some common or some unique biochemical compounds. A detailed file containing the complete information regarding the compounds is presented in the research chemical library and this file is purchasable from the relevant suppliers. These compound libraries are most advantageous in the high throughput screening assays in which the target of a drug is screened against a number of different compounds that are taking space in the library. More the number of compounds in a compound library more are the chances of getting a ‘hit’ in screening compound procedure. [Read the Full Post]

INHIBITION OF KINASES IN CANCER THERAPY

2329 | Aug 08 2012

SIGNALING VIA KINASES: Kinases are protein phosphorylating enzymes that function as gateways for the transmission of signals from extracellular to intracellular world of the cell. They stimulate the cells to carry out processes necessary for their survival, growth and proliferation etc. Different types of kinases are there in the cell for example; receptor tyrosine kinases, non-receptor tyrosine kinases, serine/threonine kinases, Histidine kinases and mixed kinases. The basic mode of action of kinases is to get activated by a signaling compound that may be a ligand or any other kinase and transmit the message to the next molecule in the form of its phosphorylation or dephosphorylation. MAP kinase is also one of the examples of such kinases. Different agonists and antagonists are there that can be used for studying the role of kinases in cell signaling. Development and production tyrosine kinase inhibitor is one of the advantages of such small compounds. Kinase assays are also there that can be used for the analysis of activity of a particular kinase in specific state. [Read the Full Post]

HIGH THROUGHPUT SCREENING IN DRUG DISCOVERIES

3237 | Jul 18 2012

HIgh throughput screening: For the treatment of life taking diseases such as cancers are always in a need to be treated with novel therapeutics, in order to full fill this task many techniques are accepted. High throughput screening is found as the most remarkable strategy in order to discover new potent drugs. Another name of this technique is High throughput screening assay and this technique is being developed more and more due to latest automatic machines which also ensures its accuracy and speed. For a drug discovery High throughput screening works under pharmaceutical, biological or biochemical environment to find out the ability of drug against specific disease. Mostly the novel drug is based on the properties of any ligand, specific receptor, peptides enzymes or ion channels involved in a specific disease condition. This is a technique with dual benefits as there is another use of high throughput screening is the detection of various pathways which are potential for specific diseases. Screening libraries of kinases is one of the most important examples of high throughput screening as compared to old techniques. [Read the Full Post]

ROLE OF HIGH THROUGHPUT SCREENING IN DRUG DISCOVERIES

3098 | Jun 07 2012

INTRODUCTION: High throughput screening is one of the novel and leading technique for the discoveries of new pharmaceutical agents for the treatment of various lethal diseases. This famous technique is also called as the High throughput screening assay, this technique has been so impressive and fast due to the advancements in automatic machines. This technique is based on the properties of different chemical agents for their ability under pharmaceuticals, biochemical and biological actions against any disorder. In the era of drug discovery this technique has been proved as the most effective for the treatment of specific diseases and these treatments are based on the drugs discovered as ligands for receptors, enzymes, proteins and ion channels. High throughput screening is also used for the detection and study of cellular or biochemical pathways for the assessment of the certain therapeutics for respective cellular mechanisms. The major example includes screening library of kinases and this is leading applied example in this regard in comparison to old methods. The importance of High throughput screening can be analyzed by studying reviews of this novel method for discovering new drugs. Business of pharmaceuticals and science and research has been greatly benefited by this method. [Read the Full Post]

HIGH THROUGHPUT SCREENING AND DRUG DISCOVERIES

3239 | May 08 2012

INTRODUCTION: In pharmaceutical industries a famous technique for discovering novel therapeutics is called as High throughput screening. This is also known as High throughput screening assay, various drugs or chemical compounds are analyzed for their potency with respect to their biological, biochemical or pharmaceutical actions by the help of unique and advanced techniques based on automatic machines. This assay has been proven as one of the most effective way of discovering new drugs against specific diseases; examples are enzyme proteins, ligands for various receptors as well as ion channels and a huge number of other pharmaceutical targets. In addition to this application High throughput screening is also being applied for the verification or detection of different biochemical or cellular mechanisms which are under investigations for therapeutic purposes such as inhibitors for different cellular pathways. [Read the Full Post]

NOVEL DRUGS AND HIGH THROUGHPUT SCREENING

1883 | Apr 09 2012

INTRODUCTION: High throughput screening assay is well known technique in pharmaceutical industries and having fame due to its role in novel drug discoveries. This is also abbreviated as high throughput screening assay, by the help of this technique or assay a good number of compounds like drugs are assessed with reference to their biochemical, biological or pharmacological activities by the aid of new automatic technologies. High throughput screening has not only proven to be effective in the field of new therapeutic agents like ligands for different receptors, enzyme proteins, ion channels and many other pharmaceutical targets, But this screening technique is also being used for profiling a cellular or biochemical pathway of interest for therapeutic targeting of this pathway by unknown compounds. The one of best example is screening libraries of kinases which are now much easier way as compared to old methods. In order to understand the value of high throughput screening one should look at reviews of this technique where accuracy and speed are the main tools which have brought the improvement in scientific research and also in the business of pharmaceutical world. [Read the Full Post]

COMPOUND LIBRARY

2128 | Apr 08 2012

INTRODUCTION OF COMPOUND LIBRARY: A pool of various compounds in a position where all these compounds can be evaluated because of the high merit of their scientific storeroom is known as a compound library. Hence compound libraries are collections of various compounds. In these libraries storage, maintenance and placing is done in a scientific way. The evolution of different new technologies in managing and designing a chemical library led to some of remarkable drug discoveries, as these libraries provide a positive procedure for research. The selection criteria for biologically active and relevant compounds and chemicals includes a huge set of synthesizable chemicals, it is an important and crucial part of research and usually needs the guidance of experts in the relevant field. These experts formulate schemes and protocols which make the selection faster and efficient than a practical chemical library. [Read the Full Post]

COMPOUND LIBRARY AND ITS UTILITY

2178 | Mar 19 2012

Introduction: The concept With the advent of the computer age a different style of thinking came into play. Technology changed the way in which scientists approached things but did not alter the rationale behind the objective. In the medical field the pressure to discover new medical treatments became a financial one rather than a humanitarian one. Pharmaceutical companies made and lost huge sums of money speculating on the potential use of a molecule for clinical purposes. To regulate all of this the USA formed the “federal drug administration” or FDA, while Europe developed the EMA. Strict rules and codes of conducted made the release of new pharmaceuticals more difficult but gave the public a greater sense of security. Pharmaceutical companies found that discovering new molecules under these rules to be an expensive proposition compared to the profits they received from the marketing the drug. Hence the competition to get a drug to the market first and claim a “lions share” of the potential profits has become the guiding rule behind drug development. Every aspect of the discovery process has been streamline to the minimize costs and every labor saving device employed to decrease expenses and increase profits. The initial stage of drug developed is the selection of a molecule or a series of molecules with biological activity. [Read the Full Post]

HIGH THROUGHPUT SCREENING FOR NEW DRUGS

3802 | Mar 18 2012

In terms of medical discovery the cost represented to a drug developing pharmaceutical company is immense; hundreds of millions of dollars can be spent in developing a new medical treatment for molecular identification to final registration after clinical trials. The “magic number” introduced in 2003 by a group of economists was $802 000 000 per new drug reaching final approval. This number has been challenged [3] but still it represents the huge financial commitment pharmaceutical companies have to make. If the drug makes it through to phase III clinical trials or even registration it can still fail due to a variety of reasons (mostly safety) and have to be withdrawn, the biggest examples of this are Vioxx (2007, Merck&co) and Thalidamide (1957, Chemie Grunenthal). The total costs to these two companies for these drugs have never been documented but it has been estimated as to be in billions. [Read the Full Post]

COMPOUND LIBRARIES AND THEIR USES

2409 | Mar 18 2012

Introduction: Concept Drug design and discovery does not happen by chance but is a process of active searching by individual scientists. Often a template molecule (of proven biological activity) will be taken and systematically altered in small ways to generate whole series of structurally related compounds. These compounds can then be either tested against the original target disease or screened against a panel of diseases to find those molecules which processes biological activity. This process is extremely labor intensive and any means by which the cost of the search or the testing for activity can reduced is actively sort. A compound library is such a labor reducing facility. A simple library will consist of information regarding properties of a number of compounds; this could include such things as structure, physical properties, chemical properties, purities or even synthesis patterns. A more complex library could be would consists if small amounts of actual compounds in known concentrations accompanied by all the known physical and chemical properties. This type library can be for the high through put screening for compounds of interest, whether they be of biological importance or synthetic chemical importance. [Read the Full Post]