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dc.contributor.author
Hauk, Stefanie
dc.contributor.author
Hiesinger, Kerstin
dc.contributor.author
Khageh Hosseini , Sabrina
dc.contributor.author
Achenbach, Janosch
dc.contributor.author
Biondi, Ricardo Miguel
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dc.contributor.author
Proschak, Ewgenij
dc.contributor.author
Zörnig, Martin
dc.contributor.author
Odadzic, Dalibor
dc.date.available
2018-06-28T17:44:41Z
dc.date.issued
2016-11
dc.identifier.citation
Hauk, Stefanie; Hiesinger, Kerstin; Khageh Hosseini , Sabrina; Achenbach, Janosch; Biondi, Ricardo Miguel; et al.; Pyrazolo[1,5a]pyrimidines as a new class of FUSE binding protein 1 (FUBP1) inhibitors; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 24; 22; 11-2016; 5717-5729
dc.identifier.issn
0968-0896
dc.identifier.uri
http://hdl.handle.net/11336/50414
dc.description.abstract
The transcriptional regulator FUSE binding protein 1 (FUBP1) is aberrantly upregulated in various malignancies, fulfilling its oncogenic role by the deregulation of critical genes involved in cell cycle control and apoptosis regulation. Thus, the pharmaceutical inhibition of this protein would represent an encouraging novel targeted chemotherapy. Here, we demonstrate the identification and initial optimization of a pyrazolo[1,5a]pyrimidine-based FUBP1 inhibitor derived from medium throughput screening, which interferes with the binding of FUBP1 to its single stranded target DNA FUSE. We were able to generate a new class of FUBP1 interfering molecules with in vitro and biological activity. In biophysical assays, we could show that our best inhibitor, compound 6, potently inhibits the binding of FUBP1 to the FUSE sequence with an IC50value of 11.0 μM. Furthermore, hepatocellular carcinoma cells exhibited sensitivity towards the treatment with compound 6, resulting in reduced cell expansion and induction of cell death. Finally, we provide insights into the corresponding SAR landscape, leading to a prospective enhancement in potency and cellular efficacy.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Fubp1
dc.subject
Pyrazolo[1,5a]Pyrimidine
dc.subject
Transcriptional Regulator
dc.subject.classification
Otras Ciencias Químicas
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dc.subject.classification
Ciencias Químicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Pyrazolo[1,5a]pyrimidines as a new class of FUSE binding protein 1 (FUBP1) inhibitors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-22T14:33:44Z
dc.journal.volume
24
dc.journal.number
22
dc.journal.pagination
5717-5729
dc.journal.pais
Países Bajos
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dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Hauk, Stefanie. Georg Speyer-haus; Alemania
dc.description.fil
Fil: Hiesinger, Kerstin. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Khageh Hosseini , Sabrina. Georg Speyer-haus; Alemania
dc.description.fil
Fil: Achenbach, Janosch. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Goethe Universitat Frankfurt; Alemania. German Cancer Consortium; Alemania
dc.description.fil
Fil: Proschak, Ewgenij. University Hospital Frankfurt; Alemania
dc.description.fil
Fil: Zörnig, Martin. Georg Speyer-haus; Alemania
dc.description.fil
Fil: Odadzic, Dalibor. Goethe Universitat Frankfurt; Alemania
dc.journal.title
Bioorganic & Medicinal Chemistry
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bmc.2016.09.015
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0968089616307027
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