discovery of small molecule regenerative drugs

... diversity of the molecules Factor analysis is widely used to study the patterns of relationship among many dependent variables, with the goal of discovering something about the nature of the independent ... and is broadly regarded as a source of ordinary molecules [45]) Seventy descriptors characterizing the structural features of these molecules were calculated, of which 13 were calculated by Sybyl ... Number of carbons atoms 0.943 -0.228 Oxygens Number of oxygen atoms 0.425 0.793 Nitrogens Number of nitrogen atoms 0.475 0.324 Sulfurs Number of sulfur atoms 0.141 -0.009 Phosphorus Number of phosphorus...

Ngày tải lên: 14/08/2014, 08:20

... ALDH3A1 is involved in metabolism of aldophosphamide (activated form of cyclophosphamide), we hypothesized that inhibition of catalytic activity of ALDH3A1 using a small molecule inhibitor will increase ... knockdown studies Selective small molecule inhibitors for these ALDH isoenzymes are not currently available We hypothesized that novel and selective small molecule inhibitors of ALDH3A1 would enhance ... ALDH3A1 in a broad–spectrum of cancer chemoresistance and support the development of selective, potent small molecule inhibitors Cyclophosphamide and its mechanism of cytotoxicity Cyclophosphamide...

Ngày tải lên: 24/08/2014, 09:51

... Type of docking ∆Gb (kcal/mol) Kd (µmol) focc Ntot Blind Fine -6.36 -6.32 22 23.3 50 93 ture of RITA and to improve the activity of a new family of potent anti-cancer drugs Conclusion The aim of ... population of 300 individuals, a maximum number of 50,000,000 energy evaluations, a maximum number of 50,000 generations, a translation step of Å, a quarternion step of 50° and a torsion step of 50° ... effectiveness of its binding to MDM2 and p53, but also to elucidate the common structural features of p53 and MDM2 in order to improve the anti-cancer activity of a new family of RITA-derived drugs Materials...

Ngày tải lên: 13/08/2014, 23:20

... NANOPARTICLES OF BIODEGRADABLE POLYMERS FOR CONTROLLED AND TARGETED DELIVERY OF PROTEIN DRUGS SMALL AND MOLECULE DRUGS BY LEE SIE HUEY (B.Sc (Hons.), NUS) A THESIS SUBMITTED FOR THE DEGREE OF MASTER ... chemotherapy is often understood in a narrower sense of treatment of cancer with drugs that can destroy cancer cells These drugs are often called anticancer drugs (http://www.cancer.gov) Anticancer drug ... bioavailability enhancer of hydrophobic drugs (Traber et al., 1994) TPGS can also enhance the oral bioavailability of anticancer drugs by improving the solubilization or emulsification of the drug in the...

Ngày tải lên: 26/11/2015, 22:41

... Identification of a small molecule inhibitor of Sir2p Proc Natl Acad Sci USA 98, 15113– 15118 53 Posakony J, Hirao M, Stevens S, Simon JA & Bedalov A (2004) Inhibitors of Sir2: evaluation of splitomicin ... physiological regulation of sirtuins by NAD+ metabolites and by enzymes in the NAD+ salvage pathway In addition, we will cover the use and efficacy of small molecule inhibitors and activators of sirtuin activity ... presence of exogenous nicotinamide [43], whereas deletion of PNC1 had the opposite effect [44] Although deletion of PNC1 did not change FEBS Journal 272 (2005) 4607–4616 ª 2005 FEBS Small molecule...

Ngày tải lên: 20/02/2014, 01:20

... identification and functional characterization of such small- molecule modulators of zymogen activation in the fibrinolytic and coagulation systems Table Small- molecule zymogen modulators identified in ... searching for small- molecule natural products that enhance the fibrinolytic system We initially aimed at identifying a candidate small molecule that could contribute to the treatment of thrombotic ... activation and fibrin binding of Glu-plasminogen, but not Lys-plasminogen Unlike the modulation of plasminogen function by other small molecules described above, the action of stachybotrydial involves...

Ngày tải lên: 06/03/2014, 22:21

... development of competitors of c-Met/HGF, monoclonal antibodies directed against HGF and c-Met, and small- molecule tyrosine kinase inhibitors directed against c-Met [8] We hypothesized that inhibition of ... Research Page of 10 10 11 12 13 14 Author details Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68105 USA 2Department of Oncology, Zhongnan Hospital of Wuhan ... expressed high levels of phospho-c-Met, the IC50 of SU11274 was 2.5 μM; whereas in the RD cell line, which expressed a lower level of phospho-c-Met, the IC 50 was over 7.5 μM The effect of SU11274 on...

Ngày tải lên: 18/06/2014, 19:20

... development of competitors of c-Met/HGF, monoclonal antibodies directed against HGF and c-Met, and small- molecule tyrosine kinase inhibitors directed against c-Met [8] We hypothesized that inhibition of ... Research Page of 10 10 11 12 13 14 Author details Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68105 USA 2Department of Oncology, Zhongnan Hospital of Wuhan ... expressed high levels of phospho-c-Met, the IC50 of SU11274 was 2.5 μM; whereas in the RD cell line, which expressed a lower level of phospho-c-Met, the IC 50 was over 7.5 μM The effect of SU11274 on...

Ngày tải lên: 20/06/2014, 03:20

... approach of identifying and studying the mechanism of action of small- molecule agonists (and antagonists), we hoped to uncover some of the complexities of the Hh-signaling system Small- molecule ... incorporate native smallmolecule ligands in the regulation of Hh signaling Results Isolation of Hh agonists by high-throughput screening To identify small- molecule agonists of Hh signaling, we ... binding of the Hh agonist to Smoexpressing cells This supports the model that all of these small- molecule modulators of Hh signaling are direct ligands of Smo We next asked whether a derivative of...

Ngày tải lên: 06/08/2014, 18:20

... 10) (a) Sum of the thickness of the right and the left hind paws of each mouse after weeks of treatment Each paw was measured twice and the average was plotted (b) Sum of the number of swollen ... incubation of cells, that secondary effects of NF-κB inhibition resulting from suppressed expression of cytokines and other regulatory molecules of cellular activity may merge with the direct effect of ... TNF-α-induced activation of JNK, or nuclear transport of Smad2 or the large T antigen This molecule should therefore be considered a unique inhibitor of NF-κB that acts at the level of nuclear translocation...

Ngày tải lên: 09/08/2014, 07:20

... structure of the (-) and (+) enantiomer of gossypol Chemical structure of the (-) and (+) enantiomer of gossypol http://www.ro-journal.com/content/4/1/47 Few studies have addressed the effect of gossypol ... chemotherapy and poor prognosis The identification of gossypol as an orally available, potent small molecule inhibitor of several anti-apoptotic members of the Bcl-2 family provides a rationally designed ... combination of stat3 decoy and AT-101 as well as the triple combination of erlotinib, stat3 decoy and AT101 showed significant enhancement of growth inhibition [26] Also in vivo the combined treatment of...

Ngày tải lên: 09/08/2014, 10:20

... inhibition of MCP-1 is secondary to the inhibition of TNF by LMP-420, since TNF can itself stimulate release of MCP-1 This pattern of cytokine/ chemokine inhibition is, of course, only representative of ... azathioprine An advantage of a small- molecule inhibitor of TNF transcription and release (such as LMP-420) over biologicals such as infliximab or etanercept is that such a molecule offers greater pharmacological ... replication of M Tb Engele et al [8] demonstrated that infection of human alveolar macrophage (AM) with virulent strains of mycobacteria induced the secretion of significantly higher levels of TNF...

Ngày tải lên: 10/08/2014, 05:20

... efficacy of small molecules on stiffness of ASM at the level of a single living cell Figure S2: Modulation of pCofilin-14-3-3 protein interactions A potential mechanism of action of small molecules ... vehicle for the delivery of small molecules Among the seven scaffolds which showed activity in the FP assay as small molecule analogs of pHSP20, only a small subset of compounds belonging to ... for the discovery of potential small molecule therapeutic agents against airflow obstruction in asthma First, we screened a library of compounds that could act as small molecule modulators of pHSP20-14-3-3...

Ngày tải lên: 12/08/2014, 13:22

... described the mechanism of action of 3-O-{3',3'-dimethylsuccinyl}-betulinic acid [DSB; referred to as YK-FH312 and PA-457 in other studies [3,4]], a small molecule inhibitor of HIV-1 replication ... cells in the presence and absence of DSB Production of the triply substituted mutant SIVm3 in the presence of DSB resulted in a small but significant accumulation of uncleaved CA-SP1, while this ... Lundquist C, Lee KH, Aiken C, Chen CH: Small- Molecule Inhibition of Human Immunodeficiency Virus Type Replication by Specific Targeting of the Final Step of Virion Maturation J Virol 2004, 78:922-929...

Ngày tải lên: 13/08/2014, 13:20

... Structure of RPA Figure 5: NMR structure of XPA Figure 6: Identification of SMIs of RPA Figure 7: Structures of SMIs of RPA Figure 8: In vitro analysis of TDRL-505 Figure 9: Cellular analysis of TDRL-505 ... response to chemotherapy 33 Small Molecule Inhibition of RPA and its Effect on DNA Replication and Repair 2.1 Introduction The identification of small molecule inhibitors of proteins is a rapidly ... Structure of SMIs of XPA identified from fluorescence anisotropy Figure 28: ELISA analysis of SMIs of XPA Figure 29: ELISA analysis of 3172-0796 on various DNA substrates Figure 30: Modeling of 3172-0796...

Ngày tải lên: 24/08/2014, 11:28

... Small Molecule Activation Small molecules are defined as molecules consisting of two to four atoms, such as CO, N2, H2O, O2, CO2 and H2 Certain small molecules, such as H2 and O2, are wells of ... a study of activation of small molecules primarily by CpMn(CO)3 The aim was to study the effect of the coordination of small molecules on cyclopentadienyl metal centers The scope 21 of the study ... of Contents Acknowledgement i Table of Contents ii viii Summary List of Tables x List of Figures xii List of Schemes xvi Abbreviations xix List of Symbols xxi CHAPTER Introduction 1.1 Small Molecule...

Ngày tải lên: 08/09/2015, 19:33

... ii TABLE OF CONTENTS Acknowledgments i Table of contents .iii Summary ix List of tables xi List of Figures xii List of Abbreviations ... of death receptors 32 2.6.1.2 Oligomerization of DRs 32 2.6.1.3 Down-regulation of c-FLIP 33 2.6.2 Modulation of the intrinsic pathway 33 2.6.2.1 Down-regulation of ... treatment of tumor cells x LIST OF TABLES Table 1: The ten human small heat shock proteins ………………………… 49 xi LIST OF FIGURES Figure 1: Apoptotic signaling Figure 2: Structure of the caspase...

Ngày tải lên: 11/09/2015, 10:14

... induce the activation of any of the caspases investigated and exposure of HeLa cells to LY30 resulted in minimal caspase activation (less than fold increase) after 6h and 12h of treatment However, ... decrease in the level of pro-caspase-3 indicating a strong activation of caspase-3 prior 93 and up to 18h This observation was confirmed by the complete cleavage of PARP after 18h of the combined treatment, ... effect of LY30 on Hsp27 phosphorylation 108 (Figure 25C) These results also indicate that most of the fraction of Hsp27 that translocates to the nucleus is phosphorylated 109 Figure 25: Effect of...

Ngày tải lên: 11/09/2015, 10:15

... Therefore, the combination of trastuzumab and small molecule anticancer drugs for the treatment of HER2 overexpressed breast cancer has been suggested as a promising means of targeted chemotherapy ... conjugation of trastuzumab on NP surface for targeted drug delivery Experiments were carried out to investigate the feasibility of the obtained NPs for targeted delivery of small molecule drugs The ... the specific characteristics of the cancer: location and grade of the cancer; the overall condition of patients and the stage of the disease; and whether the goal of treatment is to cure the cancer,...

Ngày tải lên: 14/09/2015, 08:48

... anti-DENV drug discovery Much of anti-dengue drug discovery still remains in its infant stages of identification potential antiviral candidates Small molecules or repositioned drugs that have ... resistance of HIV (Zdanowicz, 2006) As this occurs due to the high rate of viral replication coupled to the lack of proof-reading ability of reverse transcriptase which result in high mutation rates of ... 82 xii LIST OF TABLES Table 1.1 | A comparison of various in vitro protein synthesis systems 30 Table 1.2 | Summary of recently discovered anti-DENV small molecules and drugs 35 xiii Chapter...

Ngày tải lên: 04/10/2015, 16:03