Search results for "drug design and development"

showing 3 items of 3 documents

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

2021

Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer���s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited…

ABCG2 (BCRP)Multitarget inhibitor (PANABC)Broad-spectrum modulatorPolypharmacologyActivationNeurosciences. Biological psychiatry. NeuropsychiatryAmyloid-beta (Aβ / Abeta)ABCA2ABCA5ArticleABCA7InductionABCB1 (P-gp)Pattern analysisDownregulationPET Tracer (PETABC)ABC transporterABCA1 (ABC1)Rational drug design and developmentAlzheimer’s diseaseRC321-571ABCC1 (MRP1)InhibitionFree neuropathology
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Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics

2021

Graphical abstract

ATP Adenosine-triphosphateNBD nucleotide binding domainGSH reduced glutathionePolypharmacologyAlzheimer’s disease (AD)ATP-binding cassette transporterHTS high-throughput screeningBiochemistryABCA7Structural BiologyPLIF protein ligand interactionMSD membrane spanning domainPDB protein data bankTM transmembrane helixABC ATP-binding cassetteMultitarget modulation (PANABC)RMSD root mean square distanceABC transporter (ABCA1 ABCA4 ABCA7)Computer Science ApplicationsMOE Molecular Operating EnvironmentPharmacophoreSNP single-nucleotide polymorphismBiotechnologyResearch ArticleBBB blood-brain barrierBiophysicsDrug designComputational biologyBiologyAD Alzheimer’s diseasePET positron emission tomographyIC intracellular helixAPP amyloid precursor proteincryo-EM cryogenic-electron microscopyGeneticsHomology modelingBinding siteRational drug design and developmentComputingMethodologies_COMPUTERGRAPHICSNBD-cholesterol 7-nitro-2-13-benzoxadiazol-4-yl-cholesterolTransporterPSO particle swarm optimizationPET tracer (PETABC)ECD extracellular domainR-domain/region regulatory domain/regionABCA1biology.proteinEH extracellular helixTP248.13-248.65BODIPY-cholesterol 44-difluoro-4-bora-3a4a-diaza-s-indacene-cholesterolComputational and Structural Biotechnology Journal
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3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin inhibitors.

2011

During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)acrylonitrile (1) was found to be of a potency comparable to etoposide and greater than 6-mercaptopurine in all cell lines tested. Accordingly, a synthesis of a new series of (E)-2-(5,6-dichloro-1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-R-phenyl)acrylonitriles was conducted in order to extend the studies of structure-activity relationship (SAR) f…

Models MolecularMagnetic Resonance SpectroscopyMolecular modelStereochemistryAnti-cancer drugsBinding CompetitiveGas Chromatography-Mass SpectrometryAnti-cancer drugchemistry.chemical_compoundStructure-Activity RelationshipTubulinAnti-cancer drugs; drug design and development; computer assisted drug designDrug DiscoveryK562 CellmedicineStructure–activity relationshipHumansdrug design and developmentPharmacologybiologyAcrylonitrileChemistryArylOrganic ChemistryCell Cyclecomputer assisted drug designGeneral MedicineCell cycleTriazolesTubulinPodophyllotoxinCell cultureTubulin Binding Agentbiology.proteinTriazoleColchicineK562 CellsHumanmedicine.drugEuropean journal of medicinal chemistry
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