Services for RNA-targeted Drug Discovery
from the Experts in BiophysicsRNAs as drug targets
In the recent years, RNA has been recognized as much more than a simple messenger between DNA and proteins. Structured and folded RNAs are now known to be dynamic players in gene expression, pathogenesis, and cancer emergence. Conding and non-coding RNAs are thus more and more in the focus of drug discovery.
We at 2bind support this paradigm shift in drug discovery and have thus developed an array of specialized RNA-targeted drug discovery assays outlined below. These assays combine high robustness, comprehensive analysis, and the lowest sample consumption on the market, which is especially important for valuable and expensive RNA molecules.
If you are interested in specific example applications, have a look at our application notes. You can also use the contact form below to ask us anything about our RNA-targeted drug discovery services. We will get back to you shortly with a solution made specifically for your request!
Our services for RNA drug discovery
2bind offers tailor-made services and assays for the early phases of a drug discovery pipeline. In the hit identification phase, we offer true biophysical high-throughput screening with MST and Dianthus. This ensures highest throughput with minimal sample consumption and costs, all the while getting you the most important information at this step: the binding affinity.
For the hit validation phase, 2bind offers various low- and high-throughput biophysical assay formats for confirming and validating initial screening hits. This includes mainly MST, Dianthus, and nanoDSF analytics for affinity, kinetics, and thermal shifts.
Finally, for the hit characterization phase, 2bind offers a variety of specialized assay formats including MST, Dianthus, nanoDSF, BLI, and ITC technologies. These custom assays tell all important parameters of a few selected hits or lead canditates: steady-state affinity, binding kinetics, thermal shift and protein stability effects, as well as interaction thermodynamics.
Hit Identification
2bind is your one-stop shop for early RNA-targeted drug discovery and hit identification using MST, Dianthus, and nanoDSF. We cover all steps from assay development to high-throughput screening. We provide in-house compound and bioactive, tool-compound librariers as well as specialized fragment libraries. Our industry-standard compound handling features high-throughput, contact-less Labcyte Echo systems and liquid handling robots.
Comprehensive assay development for RNA targets with respect to affinity, stability, control selection, robustness, and reproducibility.
150 000 small molecule compound library
5 000 bioactive tool compound library
2 000 fragment library
Contact-less, ultrasound-based direct dilution using Labcyte Echo systems. Minimal ligand consumption (single digit nanoliters per sample).
Liquid-handling robotic platforms for preparation of screening plates and assay samples.
True biophysical hit identification and screening using high-throughput MST and Dianthus setups.
Assay Development
All the right tools for the job! We offer the full portfolio of state-of-the art biophysical assay development for MicroScale Thermophoresis and Dianthus. Our methods and assays are certified by NanoTemper Technologies (Munich, Germany). The 2bind assay development covers assay setup, establishment of required technical parameters, selection and establishment of positive and negative controls, robustness testing, and transfer to a high-throughput setup.
Liquid Handling
Put MST and Dianthus high-throughput screening to a whole new level. By using ultrasound-based, direct dilution systems (LabCyte Echo platform) for fragment and compound handling we can truly unlock the high-throughput potential of MST and Dianthus. The LabCyte Echo system enables ultra-fast, contact-less dilution of DMSO stocks with just single-digit nanoliter volumes. No plastic ware consumption, no sample carryover, no cross-contamination, and absolut minimum compound use! Read more on how the Echo system works.
High-throughput screening
True biophysical, high-throughput screening using MicroScale Thermophoresis (MST) and Dianthus. Don’t get only a yes-or-no answer for your fragments or compounds. Get their true steady-state affinity. MST and Dianthus offer the absolute lowest sample consumption for biophysical screening on the market. Screenings of thousand of compounds can be performed with just a couple of hundred microliters of valuable RNA solution.
MST
Up to 200 full, 12-point dose-response curves in 10 hours with true steady-state affinity (KD) determination.
Up to 1200 single-dose analyses in 10 hours.
> Online quality-controls (target instability, precipitation, and adhesion effects).
> Classification of binders, non-binders, fluorescent-effects, target-aggregation-inducing compounds, etc.
Dianthus
Up to 500 full, 12-point dose-response curves in 10 hours with true steady-state affinity (KD) determination.
Up to 3000 single-dose analyses in 10 hours.
> Online quality-controls (target instability, precipitation, and adhesion effects).
> Classification of binders, non-binders, fluorescent-effects, target-aggregation-inducing compounds, etc.
Special RNA-target drug discovery assays
Steady-state Binding Assay - MST, BLI, ITC
Determine the steady-state affinity (KD) of your RNA to its natural target or to any other target: ranging from ions and small molecules, over peptides, DNA, and RNA, to proteins or synthetic particles.
High-throughut Screening - MST
Analyze up to 10 000s of small molecule compounds or molecular fragments for binding to an RNA target. Fast, precise, cost-efficient, and with the lowest sample consumption on the market.
Kinetic Binding Assay - BLI
Study on- and off-rates (kon, koff) of interactions between RNAs and target molecules. Compare different aptamers with respect to their kinetic behavior using our BLI-platform.
Thermodynamic Profiling - ITC
Characterize RNA-target interactions with respect to their thermodynamics parameters including enthalpy (ΔH), free enthalpy of binding (ΔG), entropy (ΔS), and stoichiometry using ITC.
Assays in Biological Liquids - MST
Determine RNA-target interactions in relevant biological liquids such as serum, plasma, cell lysate, urine, mucose, or environmental matrices. Exclude unwanted side-interactions in these biological matrices.
Competition Assays - MST, BLI
Determine the ability of your RNA to disrupt the complex of a target molecule and its natural ligand. Alternatively, test the influence of your RNA on interactions between a target and its natural ligand.
RNA Hit Validation and Hit Characterization
Hit Validation + Hit Characterization
A number of biophysical paramters is of great intereset in the Hit Validation phase of RNA-targeted drug discovery projects. These include precise steady-state binding affinity to the screening target (KD), as well as the kinetic (kon, koff) and thermodynamic (ΔG, ΔH, ΔS) parameters of hit-target interactions. We cover all these questions with our portfolio of MST, Dianthus, BLI, and ITC methods.
In hit-to-lead stages, a lower number of drug candidates are typically analyzed with respect to more advanced binding parameters, like stoichiometry, possible competition effects, or their mode-of-action. Moreover, off-target effects have to be carefully investigated, for example by analyzing hit-target interactions in various biological liquids like serum, celly lysate, blood plasma, urine, or the like. Benefit from our higly-variable timelines and project setups to choose the right assay at the right time of the hit-to-lead phase, just as you like.
