2019
Němec, Václav; Hylsová, Michaela; Maier, Lukáš; Flegel, Jana; Sievers, Sonja; Ziegler, Slava; Schröder, Martin; Berger, Benedict-Tilman; Chaikuad, Apirat; Valčíková, Barbora; Uldrijan, Stjepan; Drápela, Stanislav; Souček, Karel; Waldmann, Herbert; Knapp, Stefan; Paruch, Kamil
Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway. Journal Article
In: Angewandte Chemie (International ed. in English), vol. 58, no. 4, pp. 1062–1066, 2019, ISSN: 1521-3773 1433-7851, (Place: Germany).
Abstract | Links | BibTeX | Tags: Binding Sites, biological activity, Cell Survival/drug effects, chemical probes, Furans/*chemistry, Hedgehog Proteins/*chemistry, heterocycles, Humans, inhibitors, Inhibitory Concentration 50, kinases, MCF-7 Cells, Molecular Structure, Protein Binding, Protein Kinase Inhibitors/*chemical synthesis/chemistry/pharmacology, Pyridines/*chemistry, Small Molecule Libraries/*chemical synthesis/chemistry/pharmacology
@article{nemec_furo32-bpyridine_2019,
title = {Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway.},
author = {Václav Němec and Michaela Hylsová and Lukáš Maier and Jana Flegel and Sonja Sievers and Slava Ziegler and Martin Schröder and Benedict-Tilman Berger and Apirat Chaikuad and Barbora Valčíková and Stjepan Uldrijan and Stanislav Drápela and Karel Souček and Herbert Waldmann and Stefan Knapp and Kamil Paruch},
doi = {10.1002/anie.201810312},
issn = {1521-3773 1433-7851},
year = {2019},
date = {2019-01-01},
journal = {Angewandte Chemie (International ed. in English)},
volume = {58},
number = {4},
pages = {1062–1066},
abstract = {Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.},
note = {Place: Germany},
keywords = {Binding Sites, biological activity, Cell Survival/drug effects, chemical probes, Furans/*chemistry, Hedgehog Proteins/*chemistry, heterocycles, Humans, inhibitors, Inhibitory Concentration 50, kinases, MCF-7 Cells, Molecular Structure, Protein Binding, Protein Kinase Inhibitors/*chemical synthesis/chemistry/pharmacology, Pyridines/*chemistry, Small Molecule Libraries/*chemical synthesis/chemistry/pharmacology},
pubstate = {published},
tppubtype = {article}
}
2009
Takacova, Martina; Holotnakova, Tereza; Vondracek, Jan; Machala, Miroslav; Pencikova, Katerina; Gradin, Katarina; Poellinger, Lorenz; Pastorek, Jaromir; Pastorekova, Silvia; Kopacek, Juraj
Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX. Journal Article
In: The Biochemical journal, vol. 419, no. 2, pp. 419–425, 2009, ISSN: 1470-8728 0264-6021, (Place: England).
Abstract | Links | BibTeX | Tags: alpha Subunit, Animals, Antigens, Aryl Hydrocarbon/genetics/metabolism/*physiology, Binding Sites, Blotting, Carbonic Anhydrase IX, Carbonic Anhydrases/genetics/*metabolism, Cell Hypoxia/genetics/*physiology, Cell Line, Chromatin Immunoprecipitation, Genetic/genetics, Humans, Hypoxia-Inducible Factor 1, Mice, Neoplasm/genetics, Polychlorinated Dibenzodioxins/pharmacology, Polymerase Chain Reaction, Promoter Regions, Protein Binding/drug effects, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction/drug effects, Tumor, Western
@article{takacova_role_2009,
title = {Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX.},
author = {Martina Takacova and Tereza Holotnakova and Jan Vondracek and Miroslav Machala and Katerina Pencikova and Katarina Gradin and Lorenz Poellinger and Jaromir Pastorek and Silvia Pastorekova and Juraj Kopacek},
doi = {10.1042/BJ20080952},
issn = {1470-8728 0264-6021},
year = {2009},
date = {2009-04-01},
journal = {The Biochemical journal},
volume = {419},
number = {2},
pages = {419–425},
abstract = {Tumour-associated expression of CA IX (carbonic anhydrase IX) is to a major extent regulated by HIF-1 (hypoxia-inducible factor-1) which is important for transcriptional activation and consists of the oxygen-regulated subunit HIF-1alpha and the partner factor ARNT [AhR (aryl hydrocarbon receptor) nuclear translocator]. We have previously observed that HIF-1alpha competes with the AhR for interaction with ARNT under conditions when both conditionally regulated factors are activated. We have therefore investigated whether TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced activation of the AhR pathway might interfere with CA IX expression. The results from the present study suggest that TCDD treatment reduces hypoxic induction of both CA IX mRNA and protein expression. Moreover, the transcriptional activity of the CA9 promoter was significantly reduced by expression of CAAhR (constitutively active AhR), which activates transcription in a ligand-independent manner. Finally, we found that ARNT is critical for both hypoxic induction and the TCDD-mediated inhibition of CA9 expression.},
note = {Place: England},
keywords = {alpha Subunit, Animals, Antigens, Aryl Hydrocarbon/genetics/metabolism/*physiology, Binding Sites, Blotting, Carbonic Anhydrase IX, Carbonic Anhydrases/genetics/*metabolism, Cell Hypoxia/genetics/*physiology, Cell Line, Chromatin Immunoprecipitation, Genetic/genetics, Humans, Hypoxia-Inducible Factor 1, Mice, Neoplasm/genetics, Polychlorinated Dibenzodioxins/pharmacology, Polymerase Chain Reaction, Promoter Regions, Protein Binding/drug effects, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction/drug effects, Tumor, Western},
pubstate = {published},
tppubtype = {article}
}