Mostrar el registro sencillo del ítem
dc.contributor.author
Pecci, Adali
dc.contributor.author
Alvarez, Lautaro Damian
dc.contributor.author
Presman, Diego Martin
dc.contributor.author
Burton, Gerardo
dc.date.available
2018-05-11T21:11:12Z
dc.date.issued
2016-06
dc.identifier.citation
Pecci, Adali; Alvarez, Lautaro Damian; Presman, Diego Martin; Burton, Gerardo; 21-Hydroxy-6,19-epoxyprogesterone: A promising therapeutic agent and a molecular tool for deciphering glucocorticoid action; Bentham Science Publishers; Mini-reviews In Medicinal Chemistry; 18; 5; 6-2016; 428 - 438
dc.identifier.issn
1389-5575
dc.identifier.uri
http://hdl.handle.net/11336/44999
dc.description.abstract
Glucocorticoids are steroid hormones that exert most of their effects through their binding to the glucocorticoid receptor (GR), a ligand regulated transcription factor. Although glucocorticoids are widely used in the clinic, their usage in chronic therapies provokes severe adverse reactions. In the quest for safer glucocorticoids a dissociated model was established that proposes a disconnection between GR activated pathways responsible of desired pharmacological effects and pathways involved in adverse GR reactions. Under this model, a myriad of steroidal and non-steroidal compounds has been characterized, with most of them still producing side effects. X-ray crystallographic studies followed by molecular dynamics analysis led research to insights on the receptor Ligand Binding Domain (LBD), which undergoes specific ligand dependent conformational changes that influence receptor activities. In this sense, the flexibility of the ligand structure would contribute to the final GR outcome. Here, we review different data of 21-hydroxy-6,19-epoxyprogesterone (21OH-6,19OP), a rigid steroid with potential pharmaceutical interest due to its anti-inflammatory and immunosuppressive activities, lacking several GR adverse reactions. The rigid structure endows this compound with an enhanced selectivity towards GR. Molecular characterization of the GR/21OH-6,19OP complex revealed specific intermediate conformations adopted by the receptor that would explain the influence on GR dimerization and the recruitment of a specific set of GR transcription modulators. We summarize recent data that will contribute to understand the complexity of glucocorticoid response
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Bentham Science Publishers
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Glucocorticoid Receptor
dc.subject
Antiglucocorticoid
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
21-Hydroxy-6,19-epoxyprogesterone: A promising therapeutic agent and a molecular tool for deciphering glucocorticoid action
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-05-11T20:54:56Z
dc.journal.volume
18
dc.journal.number
5
dc.journal.pagination
428 - 438
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Oak Park
dc.description.fil
Fil: Pecci, Adali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Alvarez, Lautaro Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
dc.description.fil
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. National Cancer Institute; Estados Unidos
dc.description.fil
Fil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
dc.journal.title
Mini-reviews In Medicinal Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/138552/article
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.2174/1389557516666160118112313
Archivos asociados