Original Agenda
We are actively working with our speakers to confirm their availability for the virtual event. Initial response from our speakers has been very positive, and we are optimistic we will have the new programs ready to share here soon.

RNA as a Small Molecule Target, August 28 2020, San Diego, CA

Cambridge Healthtech Institute’s Inaugural

RNA as a Small Molecule Target

Expanding the Boundaries of Druggable Targets


RNA molecules are crucial for delivering cellular information and genetic regulation, but until recently, the drug discovery world has emphasized protein drug targets. Our lack of knowledge in RNA biology prevented us from exploring possibilities of RNA drug targets, but with recent advances in technologies, such as sequencing, new therapeutic strategies are being explored. Join us at the Inaugural RNA as a Small Molecule Target symposium, part of Drug Discovery Chemistry, as we discuss methods and tools to identify specific, potent, novel, small molecule binders of RNA.

Final Agenda

Friday, AUGUST 28

8:00 am Registration Open and Morning Coffee


8:25 Welcome and Opening Remarks

Tanuja Koppal, PhD, Senior Conference Producer, Cambridge Healthtech Institute

Amanda Hargrove, PhD, Assistant Professor of Chemistry, Duke University

8:30 Repurposing Tools for RNA – And What to Consider When Doing It

Jenifer KaplanJenifer Kaplan, PhD, Scientist II, Biophysics and Assay Development, Arrakis Therapeutics

The identification of drug-like small molecule medicines that directly bind to RNA and modulate its biological function will vastly increase our therapeutic target space, but targeting RNA comes with its own inherent challenges. The ensemble of conformations an RNA can adapt needs to be forefront when interpreting the results of biophysical and biochemical assays. We use a combination of repurposed tools to characterize the binding event and gain insight into how the ligands are interacting with the RNA target.

9:00 Deciphering Patterns in Selective Small Molecule:RNA Interactions

Amanda HargroveAmanda Hargrove, PhD, Assistant Professor of Chemistry, Duke University

To gain fundamental insights into drivers of selectivity in small molecule:RNA recognition, we analyzed patterns in RNA-biased small molecule chemical space to reveal distinct physicochemical, structural, and spatial properties for selective RNA ligands. We further used pattern recognition protocols to identify RNA topologies that can be differentially recognized by small molecules. These insights have led to improved recognition of medicinally relevant RNA targets, including viral and long noncoding RNA structures.

9:30 Networking Coffee Break


10:00 Targeting Pre-mRNA Splicing with Small Molecules

Marla Weetall, PhD, Vice President, Pharmacology, PTC Therapeutics

Pre-mRNA splicing is emerging as a key control point in the expression of disease-modifying genes. Mutations causing alterations in splicing may result in diseases. Small molecules that affect pre-mRNA splicing have been identified and are being clinically developed. At PTC, we have developed a general approach to discover and develop drugs targeting splicing. Here we describe the application of this approach to spinal muscular atrophy, familial dysautonomia, and Huntington’s disease.

10:30 CO-PRESENTATION: Paving the Way for the Discovery of Small-Molecule Drugs Targeting the mRNAVeritas_in_Silico_New

Morishita_EllaElla Morishita, PhD, Senior Investigator, Basic Research Division, Veritas In Silico

Nakamura_ShingoShingo Nakamura, PhD, CEO, Veritas In Silico

The potential of targeting mRNAs with small molecules has been unlocked, but the path that would lead to their discovery remains unclear. We are finding druggable motifs on any given mRNA and discovering small molecules targeting them using our ibVIS-SMD platform, which combines informatics with biophysical and cellular biology approaches. Here, we will describe how the ibVIS-SMD platform enables target identification, tailored screening of chemical libraries, hit validation, and structure-based lead optimization.

11:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:00 pm Session Break


1:00 Chairperson’s Remarks

Pramod Pandey, Principal Scientist, Merck Research Labs Exploratory Science Center

1:05 Discovering Novel RNA-Binding Proteins for Small Molecule Drug Discovery

Pramod PandeyPramod Pandey, PhD, Principal Scientist, Merck Research Labs Exploratory Science Center

A large fraction of the genome is transcribed into non-coding RNAs and many of these have been implicated in influencing diseases. We are studying these in the context of diseases, relating to barrier function/dysfunction. Towards that goal, we are developing chemical biology tools to study the RNA protein interactions and find novel targets for small molecule drug discovery.

1:35 Late Breaking Presentation

2:05 FIRESIDE CHAT: What Lies Ahead?

Open Discussion with Symposia Speakers


  • How will targeting RNA revolutionize drug discovery?
  • Are there specific technologies that will help bring this around?

2:35 Networking Refreshment Break


3:05 Applying Biophysical Tools for Lead Identification, Validation and Optimization – Case Studies and Lessons Learned

Anup Upadhyay, PhD, Senior Scientist III, Drug Discovery Science & Technology, AbbVie

I will discuss how and when we use different biophysical tools (NMR, SPR, ITC, TSA and MST) to validate HTS hits, understand their binding modes and enable lead optimizations. I will present 2 to 3 different case studies from the papers that we have published recently

3:35 Dissecting the Role of 5’-triphosphate in RNA-induced Conformational Changes of Full Length RIG-I

Justyna Sikorska, PhD, Associate Principal Scientist, Mass Spectrometry & Biophysics, Merck Research Labs

Retinoic inducible gene (RIG)-I senses differences between endogenous and viral RNA for triggering immune response through induction of type I interferons. We present structural biophysical characterization of conformational signatures of 5’-ppp versus 5’-OH dsRNA bound forms of full length RIG-I. Our results were analyzed in the context of the recently published SAXS data, and laid foundation for the hypothesis that motif IVa can be involved in RIG-I activation.

4:05 Successes and Challenges in Targeting RNA with Small Molecules

Nathan BairdNathan Baird, PhD, Interim Chair, Department of Chemistry & Biochemistry, Associate Professor of Biochemistry,     University of the Sciences

Efforts targeting RNA with small molecules have been deterred by the inherent propensity of structured RNA molecules to adopt multiple conformations. The Baird Lab works to take direct advantage of RNA structural flexibility to discover small molecule inhibitors of RNA by simultaneously evaluating RNA structures and chemical screens. Our results demonstrate that targeting non-functional RNA structures is a challenging yet effective approach for therapeutic development.

4:35 Close of Symposium