Abstract: Biomolecular condensates organize cellular functions in the absence of membranes. The membrane-less organelles can form through liquid–liquid phase separation events. These molecular interactions can occur within RNA, proteins, or RNA protein complexes. The biomolecular interactions can transition into dynamic, well-defined, functional organelles in the cells. Extensive science in recent years has shown that intracellular condensates form through weak, multivalent interactions that often involve intrinsically disordered proteins or regions (IDRs). However, the nature of these interactions and how most of these organelles are organized and functional remains unknown. Aberrant condensates have been implicated in neurodegenerative diseases and a variety of cancers providing novel therapeutic opportunities for small-molecule condensate modulators.
Corelet system is a technology that was developed in the lab of Nereid co-founder Prof. Clifford P. Brangwynne and includes two modules: the GFP-tagged Core including light-inducible dimer (iLID) domains, and its associated binding partners (SspB) with an mCherry tag and IDR domain, that can be replaced by any target of interest. To mimic the oligomerization process, the Corelet system uses blue light to drive the binding event between iLID and SspB, generating IDR-containing liquid droplets. This visible, reversible droplet formation provides an easily-qualifiable high throughput approach to measuring phase separation events in cells, which was previously not possible.
At Nereid Therapeutics, we combine the state-of-the-art proprietary Corelet technology with our extensive drug discovery expertise to develop small molecules that can modulate Biomolecular Condensates. This approach combined with our high throughput screening effort has enabled us to identify potent and selective small molecules that can modulate difficult-to-drug-targets that have translatable therapeutic effects.
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