DEVELOPMENT OF NEW SELECTIVE ESTROGEN RECEPTOR MODULATORS FOR PREVENTING MENOPAUSE CONSEQUENCES

Abstract: 

Endocrine-related post-menopausal degenerative diseases are major causes of morbidity and mortality. SERMENCO aims at development, by design, synthesis and/or isolation and biological evaluation in vitro and in vivo, of natural and/or synthetic Selective Estrogen Receptor Modulators (SERMs) i.e. compounds acting as estrogen receptor (ER) agonists on the skeletal, cardiovascular and central nervous systems, where they reproduce the beneficial effects of estrogen, and as ER antagonists in the breast and uterus, thus keeping cancer risk to a minimum.

We aim at discovering natural and/or synthetic compounds for prevention and treatment of these diseases based on existing expert knowledge on,

  1. in silico modelling for evaluating drug-likeness and ADME characteristics as well as ER-binding affinity,
  2. biodiversity of constituents of edible Greek flora,
  3. technology-automated approaches of plant extraction and compound isolation, identification and structural characterization and,
  4. novel synthetic routes to develop pharmacologically potent SERMs.

Discovery of potentially active new structures will rely on previous data on,

  1. molecular modelling of a broad variety of natural and synthetic compounds deposited in own libraries and,
  2. bioactivity evaluation of plant extracts and pure compounds isolated from herbs of Mediterranean diet.

Bio-guided analysis of Greek plant extracts will result in isolation and identification of potentially active compounds, while analogues of natural and synthetic heterocyclic compounds will be also developed. Compound bioactivity will be screened using osteoblast, osteoclast, neuronal, mammary and uterine cell lines modelling key mechanisms of bone remodelling, neurodegenerative oxidative stress, breast safety and uterine cancer risk, respectively. The most active compounds in vitro will be tested for SERM-like activity using rodent models of osteoporosis and hypercholesterolemia to identify those likely to serve as drug candidates.

 

MIS 375617

Project info

Acronym:
SERMENCO
Scientific Coordinator:
Mitakou Sofia
Research Team 2 Leader:
Haroutounian Serkos
Research Team 3 Leader:
Alexis Michael N.

Stats

I.D.:
1352
Mis:
375617
Duration (months):
44
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β4ΩΚ9-ΥΒΥ

Document Library

News