Day 2 :
Keynote Forum
Thorsten Nowak
C4X Discovery
United Kingdom
Keynote: Conformational Design and its importance in drug discovery
Time : 10:00-10:30
Biography:
Thorsten Nowak completed his PhD from the University of Cambridge (UK) in the areas of aldol methodology and natural product synthesis. In 1996, he joinedrnAstraZeneca where he worked on all stages of drug discovery in medicinal chemistry as Team Leader and Project Manager. His keen interest in new technologiesrnmotivated a career move in 2012, when he joined C4X Discovery. Since he joined C4X, he has been instrumental in expanding the capabilities of C4X into appliedrndrug discovery. In his current role as Head of Medicinal Chemistry, he is leading the chemistry group and is responsible for all internal drug discovery effortsrnconducted at C4X as well as program work with our pharmaceutical partners.
Abstract:
One of the key drivers in applied medicinal chemistry which is often referred to is property based multifactorial design, at the core of which is the endeavour to harmonize a number of workflows into one. Optimization of potency, selectivity as well as ADMET properties is complex as a result of its high degree of multi-dimensionality and interdependences. Throw into the mix the question how conformations of molecules impact on properties of molecules and it becomes an almost intractable problem to solve rationally it seems. However, it is argued that detailed understanding of molecular shapes as well as the impact factors which lead to diverse conformational behaviours and the targeted manipulation of shape preferences, conformational design, are potentially an important opportunity to harness efficiencies and could make designs more effective. The talk will aim to make a case why conformational design is important, assesses some of the principals, which rationalize targeted manipulation of conformational preferences and the impact of them on biological properties of molecules.
Keynote Forum
Tatsuya Takagi
Osaka University
Japan
Keynote: Screening novel HIV-1 inhibitors targeting cyclophilin A by structure-based and ligand-based in silico study
Time : 10:30-11:00
Biography:
Tatsuya Takagi has completed his PhD from Osaka University. At that time, he had been an Assistant Professor of School of Pharmaceutical Sciences, OsakarnUniversity for 5 years. Then, since 1993, he had worked for the Genome Information Research Center, Osaka University as an Associate Professor until he becamerna Professor of Graduate School of Pharmaceutical Sciences, Osaka University in 1998. He has published more than 100 papers in reputed journals and serving asrnChairman of Division of Structure-Activity Relationship of the Pharmaceutical Society of Japan.
Abstract:
Since cyclophilin A has peptidyl-prolyl isomerase activity and binds to the capsid protein of Human Immunodeficiency Virus (HIV), it is an attractive target as an anti-HIV drug. However, just a few drugs against HIV-1 infection targeting cyclophilin A have been developed and none of them has been approved. We found a number of active compounds by in silicon structure-based screenings applying to the database with 1, 300 compounds recently. Although we found three docking sites A, B, and C, using MOE alpha site finder module, we used all of them as the docking sites because the three pockets were small. Two compounds, 12 and 23, were obtained as the most active ones. 12 covered the two docking sites, B and C, by cation-π interactions while the other covered B and C by CH-π and hydrogen bond. Especially, both of them exhibited anti-HIV activity against viral replication at low concentrations and relatively low cytotoxicity at the effective concentrations inhibiting viral growth by 50 %. As the results of comparisons between the obtained two compounds and the two controls which were called D4 and FD8, our compounds showed better results.