SC10: DIVERSITY-ORIENTED PLATFORMS FOR LIGAND DISCOVERY: FOCUSING ON DNA-ENCODED LIBRARIES
MONDAY, APRIL 8, 6:00 – 9:00 PM (DINNER PROVIDED)

This course on DNA-Encoded Library Technology (ELT) will help you gain a comprehensive overview of the platform, from library design to follow up off-DNA chemistry. During the course we will walk you through the concepts of DNA-compatible chemistry, synthesis of DNA encoded libraries using a split and pool paradigm, library complexity, the structure of the DNA coding region, and how non-amplifiable libraries are screened by affinity selection. Special emphasis will be placed on potential pitfalls during ELT process and the ways of addressing them. Attendees should come away from this course with an understanding of what ELT is and how to use it for hit identification.

Topics to be covered:

• Pros and cons of using DNA-encoded chemical libraries for small molecule hit identification
• Overview of different DNA encoded library formats
• “Split and pool” DNA recorded library synthesis strategy
• Structure of the DNA coding region and the purpose of different encoding steps in the ELT process
• Design of affinity selections to guide follow up chemistry toward hits with the desired affinity, selectivity, and mechanism of action
• Data analysis and the decision-making logic for choosing chemotypes for follow up

Instructors:

Svetlana Belyanskaya, PhD, Encoded Library Technologies, R&D Platform Technology & Science, GSK

Svetlana Belyanskaya is Scientific Leader at Encoded Library Technology (ELT) group at GlaxoSmithKline. Svetlana has been involved in the development of DNA-encoded technology at Praecis Pharmaceutical and significantly contributed in designing and adapting the DNA tagging strategies for DNA- Encoded Libraries. She led biochemistry and affinity based selection effort for several targets, partnered between GSK and Praecis Pharmaceutical. This effort resulted in the discovery of a series of potent and selective inhibitors, one of which is currently undergoing clinical trials. Post GSK acquisition, Svetlana led a team of scientists in the ELT Lead Discovery group and was responsible for ELT selections against multiple targets. Her team discovered multiple target specific small molecules with different MOAs, several of which were the first known small molecule inhibitors for novel targets.

Ghotas Evindar, PhD, Head, Post-Selection Chemistry Group, Encoded Library Technologies, R&D Platform Technology & Science, GSK

Ghotas is a site manager and chemistry group leader in the DNA encoded library technology (ELT) division of GlaxoSmithKline (GSK) in Cambridge, Massachusetts. He was born and raised in Kurdistan mountains before migrating to Canada. He completed his undergraduate and MSc degrees at the University of Waterloo, concentrating on synthesis and structureactivity studies of antifungal natural products aureobasidins. He then joined Vertex Pharmaceuticals, in Cambridge, as a medicinal chemist. While at Vertex, he was instrumental in the success of P38 MAP Kinase (first and second generation), ICE-1 inhibitors (second generation), and early ZAP-70 programs. These efforts led to discovery of four clinical candidates, VX-745, VX-765, VX-954 and VX-702. After 4 years at Vertex, he then moved to the University of Toronto to pursue a PhD degree in organic chemistry with focus on “Novel Approaches to Synthesis of Nitrogen Containing Heterocycles”. After completing his PhD with Dr. Robert Batey, he moved back to Boston area to join Praecis Pharmaceuticals as a staff scientist to lead the medicinal chemistry sphingosine-1-phosphate (S1P) receptor agonist discovery program. His team’s efforts led to candidate selection of GSK1842799A that was transitioned into GSK as part of Praecis acquisition in 2007. He has worked on DNA encoded library technology from the inception of the platform and has led different group activities within the platform over the past 14 years. Ghotas has authored well 50 publications and patents in the area of drug discovery and platform development over the last 20 years.