Arrakis is on a path to bring powerful new RNA-targeted small molecule (rSM) therapies to millions of patients.

Arrakis RNA-targeted Small-Molecule (rSM) Platform

Our proprietary platform for the systematic discovery and design of RNA-targeted small molecules (rSMs) integrates leading‐edge RNA bioinformatics and chemical biology tools, RNA‐specific chemical and biological assays, and RNA-directed medicinal chemistry. By leveraging the best existing tools with Arrakis’ exclusive technologies—TRYST, MARS and PEARL-Seq—we can, for the first time on an industrial scale, identify small molecules that modulate RNA function and predictably impact important biology in disease processes.

The value of this platform is embodied in our proprietary database of hundreds of RNA targets whose structures have been determined in dozens of different human cell lines. Each target is annotated with in-house biological data and prioritized for screening using curated libraries with the potential to initiate dozens of new therapeutic programs per year. Our first four programs are underway.

Click to explore our platform for discovering and developing rSMs:



computational analysis
structural analysis
functional relevance


primary HTS
secondary HTS
virtual screening


primary HTS
secondary HTS
virtual screening


effect of ligands on RNA structure
in vitro translation
cellular assays


binding site determination
selectivity across transcriptome
target engagement in cells


About rSMs

RNA-targeted small molecules (rSMs) are chemically based small molecules that modulate the expression level of proteins by impacting processing, transport, stability, or translation of their encoding RNAs. By selectively binding to functionally important regions in the RNA, rSMs can increase or decrease the levels of the target protein to treat disease.

TRYST™ Predicts Structures and Binding Pockets

TRYST™ is a novel sequence-to-structure engine for identifying and prioritizing novel RNA targets. It is a high-throughput, comprehensive system of bioinformatics concepts and tools, assays, and chemical libraries. SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) techniques are used to confirm the structures that emerge from TRYST. To enhance SHAPE analysis, we have developed SHAPEware™, a computational tool that we have made publicly available.


MARS is a toolbox of assays, approaches and technologies that allow for efficient analysis of the function of RNA substructures in vitro and in cells.


The identification of functional and therapeutically compelling RNA structures enables screening against those structures using curated libraries to identify small-molecule ligands. We have optimized multiple screening platforms for a survey of RNA structures, often testing high-value targets across all those platforms.


Screening yields candidate ligands binding to RNA structures, but it is essential to confirm specific RNA/ligand interactions using multiple distinct biophysical techniques. These methods include surface plasmon resonance (SPR), size-exclusion chromatography-mass spectrometry (SEC-MS), and nuclear magnetic resonance (NMR).

Having established molecular interaction, it is essential to demonstrate that binding of that RNA sub-structure impacts the biological function of the RNA. For example, if the targeted substructure plays an important role in translation of the transcript, then hits are tested in cell-free translation, cellular assays of translational function, and protein expression.

  • effect of ligands on RNA structure
  • in vitro translation
  • cellular assays


PEARL-seq™ is a suite of chemical biology tools to elucidate the molecular mechanism of action of an RNA ligand. PEARL-seq tools enable our scientists to interrogate the secondary and tertiary structures of folded RNAs–both outside and inside of cells–to assess ligand binding site, target engagement, and selectivity of a small molecule. These data are critical to the selection of superior drug candidates for development.

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