Use this URL to cite or link to this record in EThOS:
Title: Design and synthesis of new modulators of liver receptor homologue-1
Author: Bayly, Andrew Robert
ISNI:       0000 0004 2713 5167
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
Availability of Full Text:
Access from EThOS:
Access from Institution:
Nuclear receptor (NR) liver receptor homologue-1 (LRH-1) is a potential target for the treatment of breast cancers as a consequence of its regulation of aromatase and the estrogen receptor (ER). Development of modulators of NRs historically focuses on production of high affinity small molecules that compete for binding with natural ligands at the ligand-binding pocket (LBP) of the NR ligandbinding domain (LBD). Ligand-bound NRs induce transcriptional activity by subsequent recruitment of coactivator proteins. The majority of this thesis describes approaches towards the development of the first antagonists of LRH-1. In the first instance, small molecules that bind at the LBP of the receptor were developed through use of ligand-based virtual screening (VS) programs Cresset and SHop. Secondly, small molecules that directly disrupt the binding of cofactor proteins to the NR activation function-2 (AF-2) were developed through use of rational design and further Cresset VS.
Supervisor: Spivey, Alan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral