Research activities

1)Ongoing Projects

Development of novel Autotaxin inhibitors with drug-like properties against idiopathic pulmonary fibrosis (IPF). This is a collaborative project with the group of Dr. Vassilis Aidinis at Fleming.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease that is often fatal within 3-5 years after initial diagnosis. It is associated with increasing cough and dyspnea and impaired quality of life. IPF affects ∼5 million people worldwide, with incidence increasing dramatically with age. Despite extensive research efforts, its etiology in humans still remains elusive, reflecting to a significant health burden and unmet therapeutic need. Two small-molecule anti-fibrotic drugs, pirfenidone and nintedanib, have been recently adopted for IPF, however their low efficacy and side effects render them insufficient to successfully treat this disease. Long-term innovative research elegantly designed and conducted by Dr Aidinis’ lab at FLEMING in specialized experimental animal models and clinical tissue samples underlined the role of ATX and LPA as a driving force in the pathogenesis of IPF in both mice and affected patients. These experimental genetic and pharmacological studies provided the scientific basis for the regulatory and crucial role of ATX in IPF as well as the proof-of-principle for the development of ATX inhibitors for clinical and therapeutic applications. The present project concerns the pharmacological optimization of structurally new Autotaxin inhibitor leads, identified by applying cheminformatics tools and in vitro enzymatic assays. The aim of this approach is to appropriately tune the skeletal, substituent and conformational features of the new leads through application of a molecular diversity-oriented Structure-Activity Relationship (SAR) strategy. That part is accompanied by in vitro, ex vivo, Pharmacokinetic/Pharmacodynamic (PK/PD), toxicity and in vivo studies aiming at evaluating the bio-efficacy and safety profile of the best derivatives. In this context, our approach stands at the cutting-edge research for novel therapies against IPF and aspires to create promising novel advanced leads for clinical applications.

Drug repositioning application followed by Medicinal Chemistry approaches towards the development of new chemical entities for rheumatoid arthritis intervention. This is a collaborative project with the group of Dr. George Kollias at Fleming.

Drug repositioning is the process of redeveloping an already approved drug or abandoned compounds for use in a different disease. Drug repositioning is underpinned by the fact that common molecular pathways contribute to many different diseases, while it has many advantages over traditional de novo drug discovery approaches in that it can significantly reduce the cost and development time. It was found that a known drug being used against depression exhibits also a moderate but statistically significant activity in a rheumatoid arthritis mouse model. Using this drug as a starting point, our goal is to remodel its structure so as to refine those structural determinants providing potent anti-arthritis molecules with drug-like properties. This project is also multidisciplinary in nature, combining design, synthesis and in vitro and in vivo pharmacological evaluation.

 

Near-future Projects 

1)Development of molecules interfering with the regulation of the circadian rhythm as a novel approach against liver fibrosis and chronic gut inflammation.

2)Targeted delivery of bioactive molecules to brain-mitochondria as a novel approach against Neurodegenerative Diseases. 

 

B.S.R.C. "Alexander Fleming"
34 Fleming Street, 16672 Vari, Greece
Contact us - Privacy Policy