Search results for " microscale thermophoresis"

showing 2 items of 2 documents

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

2019

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…

PBD Polo box domainMTD maximal tolerance doseCDC25 cell division cycle 25HIF-1α hypoxia-inducible factor 1 αMST microscale thermophoresisIC50 50% inhibition concentrationMFP M phase promoting factorPARP-1 poly(ADP-ribose) polymerase-10302 clinical medicineFOXO forkhead box ONec-1 necrostatin 1CDC2 cell division cycle protein 2 homologGeneral Pharmacology Toxicology and PharmaceuticsMitotic catastropheCDK cyclin-dependent kinase0303 health sciencesChemistryPolo-like kinaseMono-targeted therapyCell cycleBUBR1 budding uninhibited by benzimidazole-related 1Polo box domain030220 oncology & carcinogenesisPLK1 Polo-like kinaseNecroptosisSpindle damagePLK1IHC immunohistochemistryOriginal articleNecroptosisCell cyclePLK1APC/C anaphase-promoting complex/cyclosomePLK3ABC avidin-biotin complexPI propidium iodide03 medical and health sciencesFBS fetal bovine serumPDB Protein Data BankKd the dissociation constantKinase activity030304 developmental biologyAkt/PKB signaling pathwayCell growthlcsh:RM1-950LC3 light chain 3lcsh:Therapeutics. PharmacologyCancer researchDAPKs death-associated protein kinase3-MA 3-methyladenineDAPI 4′6-diamidino-2-phenylindoleSAC spindle assembly checkpointActa Pharmaceutica Sinica B
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The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor

2021

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …

0301 basic medicineBiFC bimolecular fluorescence complementationMST microscale thermophoresisPDIA1 protein disulfide isomerase family A member 1ApoptosisNEUROTROPHIC FACTOR MANFEndoplasmic ReticulumBiochemistryprotein-protein interactionMiceBimolecular fluorescence complementationUPR unfolded protein responseENDOPLASMIC-RETICULUM STRESSMesencephalonNeurotrophic factorsInsulin-Secreting CellsProtein Interaction MappingBINDINGCOMPREHENSIVE RESOURCEATF6unfolded protein response (UPR)PDIA6 protein disulfide isomerase family A member 6PPIs protein-protein interactionsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsNPTN neuroplastinbiologyChemistryapoptosisunfolded protein responsedopamine neurons3. Good healthCell biologyGDNF glial cell line–derived neurotrophic factorIRE1-ALPHASBD substrate-binding domainendoplasmic reticulum stressMANF mesencephalic astrocyte-derived neurotrophic factorTm tunicamycinneuroprotectionResearch ArticleProtein BindingSignal TransductionGRP78Protein Disulfide-Isomerase FamilyCell SurvivalTH tyrosine hydroxylasePrimary Cell CultureSCG superior cervical ganglionProtein Disulfide-IsomerasesIRE1 inositol-requiring enzyme 1ER-STRESSER endoplasmic reticulum03 medical and health sciencesohjelmoitunut solukuolemaC-MANF C-terminal domain of MANFCSPs chemical shift perturbationsAnimalsHumansHSP70 Heat-Shock ProteinsNerve Growth FactorsNBD nucleotide-binding domainNMR nuclear magnetic resonanceMolecular Biology030102 biochemistry & molecular biologyBIPATF6Dopaminergic NeuronsGene Expression ProfilingBinding proteinneuronal cell deathDISSOCIATIONCell BiologyNEI nucleotide exchange inhibitorEmbryo MammalianadenosiinitrifosfaattiATPhermosolutmesencephalic astrocyte-derived neurotrophic factorprotein–protein interactionPERK protein kinase RNA-like ER kinaseHEK293 Cells030104 developmental biologyGene Expression RegulationChaperone (protein)Tg thapsigarginbiology.proteinUnfolded protein responseAP-MS affinity purification mass spectrometry1182 Biochemistry cell and molecular biologyGFP-SH SH-tagged GFPendoplasmic reticulum stress (ER stress)DA dopaminemesencephalic astrocyte-derived neurotrophic factor (MANF)proteiinitNeuroplastin
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