Search results for "Heat shock protein 90"

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Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening

2013

The design through energy-based pharmacophore virtual screening has led to aminocyanopyridine derivatives as efficacious new inhibitors of Hsp90. The synthesized compounds showed a good affinity for the Hsp90 ATP binding site in the competitive binding assay. Moreover, they showed an excellent antiproliferative activity against a large number of human tumor cell lines. Further biological studies on the derivative with the higher EC50 confirmed its specific influence on the cellular pathways involving Hsp90.

AminopyridinesInhibitory Concentration 50Structure-Activity RelationshipUser-Computer InterfaceHeat shock proteinCell Line TumorSettore BIO/10 - BiochimicaDrug DiscoveryHumansHSP90 Heat-Shock ProteinsBinding siteVirtual screeningheat shock protein 90 inhibitors energy-based pharmacophore virtual screening cell cycle antiproliferative activitybiologyChemistryHsp90Combinatorial chemistrySettore CHIM/08 - Chimica FarmaceuticaHuman tumorMolecular Docking SimulationCell cultureDrug DesignEnergy basedbiology.proteinMolecular MedicinePharmacophoreDrug Screening Assays Antitumor
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4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors.

2014

Hsp90 is considered an interesting therapeutic target for anticancer drug development. Here we describe a new class of 4,5,6,7-tetrahydro-isoxazolo-[4,5-c]-pyridine compounds. A small library of derivatives has been synthesized and investigated. Some reported compounds show interesting properties combining both notable binding to Hsp90 and potent cell growth inhibitory activity. N-5 substitution with a 2,4 resorcinol carboxamide appears crucial for activity. Moreover, a derivative bearing a hydroxamic acid residue bound to C-3 amide portion was found to inhibit both Hsp90 and HDAC6.

Spectrometry Mass Electrospray IonizationMagnetic Resonance Spectroscopymedicine.drug_classStereochemistryPyridinesCarboxamideApoptosisResorcinolAnti-cancer drugschemistry.chemical_compoundResidue (chemistry)AmideDrug DiscoveryHeat shock protein 90 Anti-cancer drugs 4567-Tetrahydro-isoxazolo-[45-c]- pyridinesmedicineCytotoxic T cellHumansHeat shock protein 90HSP90 Heat-Shock ProteinsPharmacologyHydroxamic acidChemistryCell growthOrganic ChemistryGeneral MedicineNuclear magnetic resonance spectroscopy4 5 6 7-Tetrahydro-isoxazolo-[4 5-c]-pyridinesFlow CytometrySettore CHIM/08 - Chimica Farmaceuticahsp90Settore BIO/14 - Farmacologia4 5 6 7-Tetrahydro-isoxazolo-[4 5-c]-pyridines; Anti-cancer drugs; Heat shock protein 90;K562 CellsCell DivisionEuropean journal of medicinal chemistry
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