Bibliografías temáticas / Geldanamycin

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Literatura académica sobre el tema "Geldanamycin"

Autor: Grafiati
Publicado: 4 de junio de 2021
Última modificación: 25 de abril de 2022

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Artículos de revistas sobre el tema "Geldanamycin"

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Martín, Juan F., Angelina Ramos y Paloma Liras. "Regulation of Geldanamycin Biosynthesis by Cluster-Situated Transcription Factors and the Master Regulator PhoP". Antibiotics 8, n.º 3 (30 de junio de 2019): 87. http://dx.doi.org/10.3390/antibiotics8030087.

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Geldanamycin and the closely related herbimycins A, B, and C are benzoquinone-type ansamycins with antitumoral activity. They are produced by Streptomyces hygroscopicus var. geldanus, Streptomyces lydicus and Streptomyces autolyticus among other Streptomyces strains. Geldanamycins interact with the Hsp-90 chaperone, a protein that has a key role in tumorigenesis of human cells. Geldanamycin is a polyketide antibiotic and the polyketide synthase contain seven modules organized in three geldanamycin synthases genes named gdmAI, gdmAII, and gdmAIII. The loading domain of GdmI activates AHBA, and also related hydroxybenzoic acid derivatives, forming geldanamycin analogues. Three regulatory genes, gdmRI, gdmRII, and gdmRIII were found associated with the geldanamycin gene cluster in S. hygroscopicus strains. GdmRI and GdmRII are LAL-type (large ATP binding regulators of the LuxR family) transcriptional regulators, while GdmRIII belongs to the TetR-family. All three are positive regulators of geldanamycin biosynthesis and are strictly required for expression of the geldanamycin polyketide synthases. In S. autolyticus the gdmRIII regulates geldanamycin biosynthesis and also expression of genes in the elaiophylin gene cluster, an unrelated macrodiolide antibiotic. The biosynthesis of geldanamycin is very sensitive to the inorganic phosphate concentration in the medium. This regulation is exerted through the two components system PhoR-PhoP. The phoRP genes of S. hygroscopicus are linked to phoU encoding a transcriptional modulator. The phoP gene was deleted in S. hygroscopicus var geldanus and the mutant was unable to grow in SPG medium unless supplemented with 5 mM phosphate. Also, the S. hygroscopicus pstS gene involved in the high affinity phosphate transport was cloned, and PhoP binding sequences (PHO boxes), were found upstream of phoU, phoRP, and pstS; the phoRP-phoU sequences were confirmed by EMSA and nuclease footprinting protection assays. The PhoP binding sequence consists of 11 nucleotide direct repeat units that are similar to those found in S. coelicolor Streptomyces avermitilis and other Streptomyces species. The available genetic information provides interesting tools for modification of the biosynthetic and regulatory mechanisms in order to increase geldanamycin production and to obtain new geldanamycin analogues with better antitumor properties.
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Clevenger, Randell C., Joseph M. Raibel, Angela M. Peck y Brian S. J. Blagg. "Biotinylated Geldanamycin". Journal of Organic Chemistry 69, n.º 13 (junio de 2004): 4375–80. http://dx.doi.org/10.1021/jo049848m.

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SAUSVILLE, E. A. "Geldanamycin Analogs". Journal of Chemotherapy 16, sup4 (noviembre de 2004): 68–69. http://dx.doi.org/10.1179/joc.2004.16.supplement-1.68.

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Dhayapulay, Akhila y Mathumai Kanapathipillai. "Exosomes Based Geldanamycin Delivery to Cancer Cells with Increased Therapeutic Efficacy". Journal of Biomedical Nanotechnology 15, n.º 11 (1 de noviembre de 2019): 2202–8. http://dx.doi.org/10.1166/jbn.2019.2844.

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HSP90 has been shown to promote oncogenic functions and cell proliferation during tumor progression. Geldanamycin is a potent inhibitor of HSP90, however therapeutic effects are often hampered due to its extreme hydrophobicity and systemic toxicity. Hence targeted delivery strategies are needed to overcome these limitations and to improve the efficacy of the drug. Here we utilize a novel geldanamycin delivery approach by utilizing exosomes. For the study, exosomes were extracted from cancer cells, loaded with geldanamycin, and the therapeutic effects were tested in cancer cells. Results show that cancer cells derived exosomes exhibit specificity to cancer cells. Further exosomes loaded geldanamycin show several fold increase in efficacy compared to free geldanamycin. Findings indicate exosomal formulations could be used for extremely hydrophobic HSP90 inhibitor geldanamycin delivery for inhibiting cancer cell proliferation.
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Kiang, Juliann G., Phillip D. Bowman, Xinyue Lu, Yansong Li, Brian W. Wu, Horace H. Loh, K. T. Tsen y George C. Tsokos. "Geldanamycin inhibits hemorrhage-induced increases in caspase-3 activity: role of inducible nitric oxide synthase". Journal of Applied Physiology 103, n.º 3 (septiembre de 2007): 1045–55. http://dx.doi.org/10.1152/japplphysiol.00100.2007.

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Hemorrhage has been shown to increase inducible nitric oxide synthase (iNOS) and deplete ATP levels in tissues and geldanamycin limits both processes. Moreover, it is evident that inhibition of iNOS reduces caspase-3 and increases survival. Thus we sought to identify the molecular events responsible for the beneficial effect of geldanamycin. Hemorrhage in mice significantly increased caspase-3 activity and protein while treatment with geldanamycin significantly limited these increases. Similarly, geldanamycin inhibited increases in proteins forming the apoptosome (a complex of caspase-9, cytochrome c, and Apaf-1). Modulation of the expression of iNOS by iNOS gene transfection or siRNA treatment demonstrated that the level of iNOS correlates with caspase-3 activity. Our data indicate that geldanamycin limits caspase-3 expression and protects from organ injury by suppressing iNOS expression and apoptosome formation. Geldanamycin, therefore, may prove useful as an adjuvant in fluids used to treat patients suffering blood loss.
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Mandler, Raya, Hisataka Kobayashi, Ella R. Hinson, Martin W. Brechbiel y Thomas A. Waldmann. "Herceptin-Geldanamycin Immunoconjugates". Cancer Research 64, n.º 4 (15 de febrero de 2004): 1460–67. http://dx.doi.org/10.1158/0008-5472.can-03-2485.

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Othman, A. A. y Z. S. Shoheib. "Detrimental effects of geldanamycin on adults and larvae of Trichinella spiralis". Helminthologia 53, n.º 2 (1 de junio de 2016): 126–32. http://dx.doi.org/10.1515/helmin-2016-0003.

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SummaryTrichinellosis is a zoonotic disease affecting mainly the temperate regions. The treatment is a challenge for the physician, and the available therapy is far from ideal. Therefore, this work aimed to evaluate the effect of heat shock protein 90 inhibitor, geldanamycin, on the adult worms and larvae of Trichinella spiralis. This research comprised an in vivo study in which T. spiralis-infected mice were treated by two different doses of geldanamycin, thereafter larval count and pathological changes were determined in the muscles. Meanwhile, the in vitro study investigated the effect of two different concentrations of geldanamycin on adult worms and larvae of T. spiralis via transmission electron microscopy. The in vivo study showed significant reduction of muscle larval counts under the effect of geldanamycin. Moreover, characteristic changes were noted as regards the parasite and the inflammatory response. The in vitro study revealed degenerative changes in the body wall of larvae and adults of T. spiralis under the influence of geldanamycin. In conclusion, heat shock protein 90 inhibitor, geldanamycin, seems to have detrimental effects on the adults and larvae of T. spiralis. It, or one of its derivatives, could be an adjuvant to anthelmintic therapy of trichinellosis, but more studies are warranted to establish its usefulness.
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Zhang, Zhi, Yunfeng Li, Rentao Zhang y Xiaoming Yu. "Total Synthesis of Geldanamycin". Journal of Organic Chemistry 86, n.º 21 (16 de octubre de 2021): 15063–75. http://dx.doi.org/10.1021/acs.joc.1c01582.

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Vivas-Reyes, Ricardo, Alejando Morales-Bayuelo, Carlos Gueto, Juan C. Drosos, Johana Márquez Lázaro, Rosa Baldiris, Maicol Ahumedo, Catalina Vivas-Gomez y Dilia Aparicio. "Study of interaction energies between residues of the active site of Hsp90 and geldanamycin analogues using quantum mechanics/molecular mechanics methods". F1000Research 8 (2 de diciembre de 2019): 2040. http://dx.doi.org/10.12688/f1000research.20844.1.

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Background: Heat shock protein (Hsp90KDa) is a molecular chaperone involved in the process of cellular oncogenesis, hence its importance as a therapeutic target in clinical trials. Geldanamycin is an inhibitor of Hsp90 chaperone activity, which binds to the ATP binding site in the N-terminal domain of Hsp90. However, geldanamycin has shown hepatotoxic damage in clinical trials; for this reason, its use is not recommended. Taking advantage that geldanamycin binds successfully to Hsp90, many efforts have focused on the search for similar analogues, which have the same or better biological response and reduce the side effects of its predecessor; 17-AAG and 17-DMAG are examples of these analogues. Methods: In order to know the chemical factors influencing the growth or decay of the biological activity of geldanamycin analogues, different computational techniques such as docking, 3DQSAR and quantum similarity were used. Moreover, the study quantified the interaction energy between amino acids residues of active side and geldanamycin analogues, through hybrid methodologies and density functional theory (DFT) indexes. Results: The evaluation of interaction energies showed that the interaction with Lys58 residue is essential for the union of the analogues to the active site of Hsp90, and improves its biological activity. This union is formed through a substituent on C-11 of the geldanamycin macrocycle. A small and attractor group was found as the main steric and electrostatic characteristic that substituents on C11 need in order to interact with Lys 58; behavior was observed with hydroxy and methoxy series of geldanamycin analogues, under study. Conclusion: These outcomes were supported with quantum similarity and reactivity indices calculations using DFT in order to understand the non-covalent stabilization in the active site of these compounds.
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Vivas-Reyes, Ricardo, Alejando Morales-Bayuelo, Carlos Gueto, Juan C. Drosos, Johana Márquez Lázaro, Rosa Baldiris, Maicol Ahumedo, Catalina Vivas-Gomez y Dilia Aparicio. "Study of interaction energies between residues of the active site of Hsp90 and geldanamycin analogues using quantum mechanics/molecular mechanics methods". F1000Research 8 (16 de abril de 2020): 2040. http://dx.doi.org/10.12688/f1000research.20844.2.

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Background: Heat shock protein (Hsp90KDa) is a molecular chaperone involved in the process of cellular oncogenesis, hence its importance as a therapeutic target. Geldanamycin is an inhibitor of Hsp90 chaperone activity, which binds to the ATP binding site in the N-terminal domain of Hsp90. However, geldanamycin has shown hepatotoxic damage in clinical trials; for this reason, its use is not recommended. Taking advantage that geldanamycin binds successfully to Hsp90, many efforts have focused on the search for similar analogues, which have the same or better biological response and reduce the side effects of its predecessor; 17-AAG and 17-DMAG are examples of these analogues. Methods: In order to know the chemical factors influencing the growth or decay of the biological activity of geldanamycin analogues, different computational techniques such as docking, 3DQSAR and quantum similarity were used. Moreover, the study quantified the interaction energy between amino acids residues of active side and geldanamycin analogues, through hybrid methodology (Autodock-PM6) and DFT indexes. Results: The evaluation of interaction energies showed that the interaction with Lys58 residue is essential for the union of the analogues to the active site of Hsp90, and improves its biological activity. This union is formed through a substituent on C-11 of the geldanamycin macrocycle. A small and attractor group was found as the main steric and electrostatic characteristic that substituents on C11 need in order to interact with Lys 58; behavior was observed with hydroxy and methoxy series of geldanamycin analogues, under study. Conclusion: This study contributes with new hybrid methodology (Autodock-PM6) for the generation of 3DQSAR models, which to consider the interactions between compounds and amino acids residues of Hsp90´s active site in the alignment generation. Additionally, quantum similarity and reactivity indices calculations using DFT were performed to know the non-covalent stabilization in the active site of these compounds.
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Tesis sobre el tema "Geldanamycin"

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Rosenbeiger, Daniela Katjuscha. "Studien zur Totalsynthese von Geldanamycin /". München : Verl. Dr. Hut, 2008. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=017069836&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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Hampel, Thomas Armin [Verfasser]. "Stereoselektive C,C-Kupplungsreaktionen zur Totalsynthese des HSP90 Inhibitors Geldanamycin / Thomas Armin Hampel". München : Verlag Dr. Hut, 2012. http://d-nb.info/1028783043/34.

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Allen, Ian. "The cloning and analysis of the genes specifying geldanamycin biosynthesis from Streptomyces hygroscopicus". Thesis, University of Liverpool, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333630.

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Hicken, Erik J. "Total Syntheses of (+)-Geldanamycin, (-)-Ragaglitazar, and (+)-Kurasoin A and Phase-Transfer-Catalyzed Asymmetric Alkylation". BYU ScholarsArchive, 2005. https://scholarsarchive.byu.edu/etd/801.

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Geldanamycin possesses various biological activities as seen in the NCI 60 cell line panel (13 nM avg., 70 nM SKBr-3 cells). The predominant mode of action providing these unique results arises from the ability of geldanamycin (GA) to bind to the chaperone heat shock protein 90 (Hsp90). Despite its complicated functionality, the first total synthesis of GA was accomplished, which included two new reactions developed specifically to address the stereochemical features. The final step in the synthesis of GA was a demethylation-oxidation sequence to generate the desired para-quinone. This step could only be accomplished with HNO3/AcOH, producing GA in 5% yield. A GA model study, which closely resembled the aromatic core, was extensively investigated to solve this critical oxidation issue. A protected hydroquinone model compound was determined to be the optimum choice. Using Pd in the presence of air with a 1,4-hydroquinone provided the desired para-quinone quickly and nearly quantitatively in 98% yield. This study formulated the recipe of success for para-quinone formation of GA and future synthetic analogs. Asymmetric glycolate alkylation has been developed using phase-transfer-catalysis (PTC). Diphenylmethoxy-2,5-dimethoxyacetophenone with trifluorobenzyl cinchonidinium catalyst and cesium hydroxide provided alkylation products at —35 °C in high yield (80-99%) and with excellent enantioselectivity (up to 90% ee). Useful α-hydroxy products were obtained using bis-TMS peroxide Baeyer—Villiger conditions and selective transesterification. The intermediate aryl esters can be obtained with >99% ee after a single recrystallization. The newly developed PTC glycolate alkylation was applied to the asymmetric syntheses of ragaglitazar and kurasoin A. Ragaglitazar is a potent antihyperglycemic and lipid modulator, currently in phase II clinical trials. Kurasoin A is a relatively potent protein farnesyltransferase (PFTase) inhibitor with an IC50 value of 59.0 micromolar. PTC glycolate alkylation was optimized to provide 4-benzyloxy glycolate intermediates in excellent overall yield and with 96% ee after recrystallization. Ragaglitazar was then synthesized after considerable experimentation to provide the potent lipid modulator with yields and enantiopurity rivaling the best-known routes produced by industry standards. Kurasoin A was produced through an α-triethylsiloxy Weinreb amide to provide the highest overall yielding route to this PFTase inhibitor currently disclosed.
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Schröder, Benjamin [Verfasser]. "Synthese unnatürlicher Farnesylderivate als Substrate für Sesquiterpenzyklasen – Mutasynthetischer Zugang zu heteroaromatischen Geldanamycin-Derivaten / Benjamin Schröder". Hannover : Gottfried Wilhelm Leibniz Universität, 2018. http://d-nb.info/1172414122/34.

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Wang, Yong. "Total Synthesis of 4'-ester Resveratrol Analogs and 8.9-amido Geldanamycin Analog and Toward the Total Synthesis of (-)-englerin A". BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/3084.

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Total Synthesis of 4'-ester Resveratrol Analogs and 8, 9-amido Geldanamycin Analog and toward the Total Synthesis of (-)-Englerin A Yong Wang Department of Chemistry and Biochemistry, BYU Doctor of Philosophy The phytoalexin resveratrol and its 4'-ester analogs have been prepared with a decarbonylative Heck reaction. The deprotecting step has been modified and improved to increase yield and avoid chromatography. A set of resveratrol analogs and resveratrol have been tested with melanoma and pancreatic cell assays. The 8, 9-amido Geldanamycin analog has been synthesized with a convergent route, involving 28 simplified steps in its longest linear sequence. Synthetic methodologies, such as Andrus auxiliary controlled asymmetric anti-glycolate Aldol and selective p-Quinone formation, were employed. The total synthesis of Englerin A starts from (R)-carvone, passed through the modified Farvoskii ring-contraction and ring closing metathesis to get the ring skeleton. Other routes involving isopropyl group installation before closure of the seven-member ring failed. Although there are still problems to build the isopropyl moiety and the bridged ether, several reasonable alternative routes to address the problems have been designed.
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Scherer, Brooklynn M. "Determining the Effect of HSP90 Inhibitor Geldanamycin on Herpes Simplex Virus Type-1 Production in Infected Vero Cells". Walsh University Honors Theses / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=walshhonors1555679860864038.

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Liu, Jing. "Synthesis of Resveratrol and Its Analogs, Phase-Transfer Catalyzed Asymmetric Glycolate Aldol Reaction, and Total Synthesis of 8,9-Methylamido-Geldanamycin". BYU ScholarsArchive, 2007. https://scholarsarchive.byu.edu/etd/1415.

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The phytoalexin resveratrol and its acetyl analogs have been made using a decarbonylative Heck reaction. The acid chloride derived from 3,5-dihydroxybenzoic acid was coupled with suitable protected 4-hydroxystyrene in the presence of palladium acetate and N,N-bis-(2,6-diisopropylphenyl)-4,5-dihydro imidazolium chloride to give the substituted stilbene in good yield as the key step. Human HL-60 cell assays showed the 4'-acetyl resveratrol variant improved activity (ED50 17 μM) relative to resveratrol (24 μM). Cinchona phase-transfer catalysts (PTC) were developed for glycolate aldol reactions to give differentially protected 1,2-diol products. Silyl enol ether of diphenylmethoxy-2,5-dimethoxyacetophenone reacted to generate benzhydryl-protected products. O-Allyl trifluorobenzyl cinchonium hydrodifluoride (20 mol %) catalyzed the addition of the silyl enol ether to benzaldehyde to give aldol product as a single syn-product in 76% yield and 80% ee. Recrystallization enriched the product to 95% ee, and a Baeyer-Villiger reaction transformed the product into useful ester intermediates. A novel unnatural product, 8,9-Methylamido-Geldanamycin, has been designed and synthesized. Using a convergent route, the total synthesis of the molecule involved only 27 longest linear steps. New synthesis methodologies, including auxiliary controlled asymmetric anti-glycolate aldol, syn-norephedrine aldol, and selective p-quinone formation, were used.
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Schroyer, April L. "The Regulation of Mixed Lineage Kinase 3 by Extracellular Signal-Regulated Kinases 1 and 2 and Stress Stimuli in Colorectal and Ovarian Cancer Cells". University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513345931716064.

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Hampel, Thomas [Verfasser], Thorsten [Akademischer Betreuer] Bach y Klaus [Akademischer Betreuer] Köhler. "Stereoselektive C,C-Kupplungsreaktionen zur Totalsynthese des HSP90 Inhibitors Geldanamycin / Thomas Hampel. Gutachter: Thorsten Bach ; Klaus Köhler. Betreuer: Thorsten Bach". München : Universitätsbibliothek der TU München, 2012. http://d-nb.info/1034134833/34.

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Capítulos de libros sobre el tema "Geldanamycin"

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Neckers, L. "Chaperoning Oncogenes: Hsp90 as a Target of Geldanamycin". En Molecular Chaperones in Health and Disease, 259–77. Berlin, Heidelberg: Springer Berlin Heidelberg, 2006. http://dx.doi.org/10.1007/3-540-29717-0_11.

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Manaenko, Anatol, Nancy Fathali, Shammah Williams, Tim Lekic, John H. Zhang y Jiping Tang. "Geldanamycin Reduced Brain Injury in Mouse Model of Intracerebral Hemorrhage". En Intracerebral Hemorrhage Research, 161–65. Vienna: Springer Vienna, 2011. http://dx.doi.org/10.1007/978-3-7091-0693-8_27.

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Karabiyikoglu, Murat, Ya Hua, Richard F. Keep y Guohua Xi. "Geldanamycin Treatment During Cerebral Ischemia/Reperfusion Attenuates p44/42 Mitogen-Activated Protein Kinase Activation and Tissue Damage". En Brain Edema XV, 39–43. Vienna: Springer Vienna, 2013. http://dx.doi.org/10.1007/978-3-7091-1434-6_6.

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Enna, S. J. y David B. Bylund. "Geldanamycin". En xPharm: The Comprehensive Pharmacology Reference, 1–2. Elsevier, 2007. http://dx.doi.org/10.1016/b978-008055232-3.63144-7.

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"Geldanamycin". En Encyclopedia of Cancer, 1868. Berlin, Heidelberg: Springer Berlin Heidelberg, 2016. http://dx.doi.org/10.1007/978-3-662-46875-3_100978.

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"Geldanamycin". En Encyclopedia of Cancer, 1516–17. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_2357.

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"Gasflaschen to Geldanamycin". En RÖMPP Lexikon Chemie, editado por Jürgen Falbe y Manfred Regitz. Stuttgart: Georg Thieme Verlag, 1997. http://dx.doi.org/10.1055/b-0036-135477.

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"Geldanamycin to Gerberei". En RÖMPP Lexikon Chemie, editado por Jürgen Falbe y Manfred Regitz. Stuttgart: Georg Thieme Verlag, 1997. http://dx.doi.org/10.1055/b-0036-135478.

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Andrus, Merritt B., Erik J. Hicken y Erik L. Meredith. "Chapter 2 Synthesis of geldanamycin using glycolate aldol reactions". En Strategies and Tactics in Organic Synthesis, 38–70. Elsevier, 2005. http://dx.doi.org/10.1016/s1874-6004(05)80025-5.

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Actas de conferencias sobre el tema "Geldanamycin"

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Rikova, Klarisa, Benjamin Hall, Anthony Possemato, Keri Mroszczyk, Kimberly A. Lee, Joan MacNeill, Jian Min Ren et al. "Abstract A94: Understanding of differing sensitivity in EML4-ALK NSCLC patients to crizotinib and geldanamycin." En Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-a94.

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Valbuena, Jose R., Juan C. Roa, Pamela A. Leal, Patricia A. Garcia y Alejandro Corvalan. "Abstract 3432: HSP90 expression and antitumoral activity of geldanamycin and its analog 17-AAG in gallbladder cancer." En Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-3432.

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Szanto, S., P. Csermely, I. Kovács, J. Csongor, GY Szegedi y S. Sipka. "THU0053 Inhibition of arachidonic acid release from human peripheral mononuclear cells by heat shock treatment and geldanamycin". En Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.850.

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Lee, Ho-Jae, Sun-Young Yoon, Thuy Trang Nguyen, Han-Yang Cho, Tae-Hyun Kim, Woo-Kwang Jeon y Byung-Chul Kim. "Abstract 3965: Geldanamycin-induced heat shock protein 70 negatively regulates TGF-β signaling through interaction with TGF-β receptors". En Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-3965.

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Shimp, Samuel K., Christopher M. Reilly y Marissa Nichole Rylander. "Empirical Modeling the Effect of Hsp90 Inhibition on Cytokines Associated With Impaired Biotransport of Apoptotic Debris". En ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19572.

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Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder that can affect nearly every organ in the body. A link has been established between abnormal biotransport of apoptotic cell debris and pathogenesis of SLE [1]. Lupus mice are hyper-responsive to immune stimulation and overproduce inflammatory mediators including IL-6, IL-12, and nitric oxide (NO) [2]. Extracellular expression and transport of inflammatory cytokines are thought to be involved with the inhibited clearance of cellular debris [1]. Hsp90 has a prominent role in folding and conformational regulation of several client proteins, including proteins involved with production of inflammatory mediators [3]. Hsp90 readily binds ATP at the amino (N-) terminal domain. This binding event causes a conformational change in Hsp90 making it “clamp down” on its client protein [3]. Geldanamycin (Geld) is a known inhibitor of Hsp90 that out competes ATP binding at the N-terminal. This prevents chaperone capability and ultimately leads to client protein deactivation, destabilization, and degradation [3]. Hsp90 inhibitors have been shown to suppress immune stimulated release of interleukin 6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and nitric oxide (NO) [4].
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Battelli, Chiara, Alexander Morse, Hai Hu, Elena Levantini, Gerburg Wulf y Panagiotis A. Konstantinopoulos. "Abstract 3339: HSP90 inhibitor 17-allylamino-geldanamycin enhances sensitivity to double-strand DNA break-inducing agents (platinum and PARP inhibitors) in epithelial ovarian cancer." En Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-3339.

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Informes sobre el tema "Geldanamycin"

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Savova, Gergana, Katya Stankova, Nevena Aneva y Rayna Boteva. Geldanamycin, Natural Benzoquinone and Inhibitor of the Molecular Chaperone Hsp90, Accelerates the Repair of DNA Doublestrand Breaks in Human Blood Cells. "Prof. Marin Drinov" Publishing House of Bulgarian Academy of Sciences, mayo de 2021. http://dx.doi.org/10.7546/crabs.2021.05.08.

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