Addressing blood-brain barrier in CNS drug discovery using fragment based approach
Journal of Proteomics & Bioinformatics

Journal of Proteomics & Bioinformatics
Open Access

ISSN: 0974-276X

Addressing blood-brain barrier in CNS drug discovery using fragment based approach

6th International Conference on Structural Biology

August 22-23, 2016 New Orleans, USA

G Sridhar Prasad

CalAsia Pharmaceuticals, Inc., USA

Posters & Accepted Abstracts: J Proteomics Bioinform

Abstract :

Central nervous system (CNS) related disorders affect over one billion people worldwide. The treatment cost in USA alone is expected to be over $600 billion per year with an economic impact exceeding over a trillion dollar. The two major challenges that impact the treatment of CNS diseases are: (i) effective delivery of drugs and (ii) discovery and development of drug molecules that can cross the blood-brain barrier. Given the fact, that CNS drugs require a more restricted profile of molecular properties (MW: <450Da; LogP: â?¤4.0 and Polar Surface Area (PSA): â?¤ 80??2) than the Lipinski â??Rule of Fiveâ??, hits identified using conventional compound library (MW: 500Da; LogP: 5.5 and Polar Surface Area: 140??2) limits the possibility of evolving and optimizing them into promising lead candidates suitable for advancing into in vivo proof of concept and development studies. An efficient and alternate approach to overcome and address this limitation is to initiate the lead optimization starting with hits identified using fragment based approach and combine with rational structure-based drug design methods. We have used this approach to discover novel, potent and CNS permeable inhibitors of the molecular chaperone, Heat Shock Protein-90, which have demonstrated selective portioning into the CNS, target engagement and pharmacodynamics effects in vivo.

Biography :

Email: [email protected]