Leading Drug Discovery Through Biophysical Assays

In the pursuit of novel therapeutics, biophysical assays are relied upon to characterize potential drug-target interactions to advance the drug discovery pipeline from hit to lead. Biophysical assays provide a detailed characterization of molecular interactions, enabling researchers to optimize both affinity and specificity to prioritize drug candidates with higher chances of success. 

Types of Biophysical Assays:

Surface Plasmon Resonance (SPR)

SPR is a high-throughput technique that measures the kinetics of biomolecular interactions, including those of fragments & small molecules. The Gold Standard of biophysics. 

Isothermal Titration Calorimetry (ITC)

ITC is a truly label-free, steady-state technique to directly determine the affinity, stoichiometry, and thermodynamic parameters of biomolecular interactions. An excellent orthogonal complement to SPR. 

Bio-Layer Interferometry (BLI)

BLI is a high-throughput screening technique that can measure the kinetics and affinity of biomolecular interactions of proteins, peptides, and nucleic acids in complex matrices and without microfluidics. 

Nuclear Magnetic Resonance (NMR)

NMR spectroscopy can be used for both biosimilar comparability & CMC, in addition to fragment screening and affinity titration studies. 

Plate-Based Assays

Ichor has the capability to conduct a variety of quantitative plate-based biochemical, biophysical, and bioanalytical assays, including ELISAs and Fluorescence Polarization (FP) experiments.  

Applications of Biophysical Assays

Biophysical assays find extensive applications in various areas of research and industry, playing a crucial role in understanding and validating biological interactions in the realm of drug discovery. Some of the key applications of biophysical assays include: 

 

Target Validation: 

Prior to investing resources in developing drugs to target a specific protein or biomolecule, validation of the chosen target is needed to confirm that it is relevant and likely to produce the desired therapeutic effects. Biophysical assays are key in the validation process by reducing the system to a bimolecular interaction and providing direct and quantified evidence for the interaction. 

Drug Discovery: 

Biophysical assays are utilized for identifying and validating potential drug targets, identifying hits, and prioritizing lead compounds. Modern techniques such as SPR accelerate the drug discovery process and increase the chance of discovering safe and effective therapeutics. 

Hit Discovery: 

Biophysical assays such as SPR are ideal for early-stage drug discovery. High-throughput screening of fragment or targeted small molecule libraries allows for rapid identification of hits.  

Lead Optimization: 

Biophysical assays are crucial to the optimization of lead compounds by providing data such as binding affinity, kinetics, stoichiometry, selectivity, and stability. These data provide key insights into the chemical modifications needed for effective SAR optimization. 

Mechanism of Action: 

Biophysical assays facilitate the exploration of molecular pathways involved in drug-target interactions. They help in identifying the key players and reduce the likelihood of off-target interactions, thereby enabling the optimization of the drug's safety and efficacy. 

Molecular Interaction Mapping & Epitope Binning: 

Techniques like Surface Plasmon Resonance (SPR), Nuclear Magnetic Resonance (NMR), and X-ray crystallography enable the mapping of molecular interactions, either directly or indirectly, at the residue or epitope level. They offer detailed structural information about binding sites and specificity. This information is instrumental in guiding the design of small molecules or peptides aimed at disrupting specific interactions.  

Our speciality in biophysical assays is SPR!

Assay development, high-throughput fragment and small molecule screening, & kinetic or affinity characterization

We have state of the art Biacore 8K/8K+ SPR systems

  • High-throughput SPR screening: kinetic screening & characterization 
  • Clean, binding level, & affinity screens 
  • Epitope binning 
  • Concentration & potency analysis 
  • Personal one-on-one discussion of data and results with a Ph.D. scientist. We stand by our data! 

Assay development & target validation: feasibility and full control of characterization

Fast turnaround time – most projects are initiated within 2 weeks upon receipt of materials. 

Full ownership – client retains full ownership of all raw and processed data and is entitled to all data exports and a PowerPoint presentation deliverable of data and results. 

Instrumentation

IMG_1610 (1)

Biacore 8K & 8K+ SPR systems

What’s better than a Biacore 8K? A Biacore 8K+!

BLI-6-modified

ForteBio Octet RED384

Biomolecular interaction analysis without the microfluidics.

spectramax

Molecular Devices SpectraMax i3x

Our temperature controlled plate reader is equipped with an automated high-throughput StakMax and can work with 96- or 384-well plates in absorbance, fluorescence, or chemiluminescent read modes.

ITC

TA Instruments nano-ITC & nano-DSC

The nano-series instruments only require a fraction of the protein quantity that earlier models consumed.

Bruker 800_2

Bruker AVANCE III HD 800 MHz with TCI Cryoprobe

Whether you are looking for biosimilarity comparisons, high-throughput fragment screening, isotopically enriched protein production, or NMR consultants; we have what you are looking for!

Testimonials

Client satisfaction is our measure of success

Ankyra logo

“Ichor helped us develop a custom binding assay that was critical for selection and optimization of our lead molecule. Throughout the process, the Ichor team was highly collaborative and flexible and provided high quality data in a timely manner”

– Ankyra Therapeutics

reglagene_testimonial

“In our Surface Plasmon Resonance project, Ichor’s Biophysical team demonstrated clear 1:1 stoichiometry for the binding of our lead molecule to the target protein, as well as deriving the association and dissociation rates for the binding. Ichor’s team demonstrated excellent technical expertise, strong communication skills, and was both flexible and team-oriented. We look forward to working with Ichor again on future projects." 

– Reglagene

Our biophysics projects have fast turnaround times

Most biophysics projects start within 2 weeks of receipt of materials.

FAQs

Please reach out to us with any questions or comments regarding our biophysical assays, we are here to help you.

PhD level scientists manage all of our projects, which typically commence within 2 weeks after receipt of all test articles, samples, reagents, and consumables. We take pride in our work, pay attention to details during the execution, and do not rush projects if that could compromise your data. At the end of your project, all data and reagents are yours, and you can expect to receive a PowerPoint slide deck containing all relevant conditions and data as a project deliverable. 

Our view of customer service demands that all projects, including biophysical assays, receive the dedicated attention, research, and scoping they deserve to be properly and fully quoted and executed at the highest scientific standards. We also believe in being respectful of everyone’s time. We therefore require all prospective clients to attend a brief teleconference to discuss their projects before a quote can be issued. Our quotes are custom-built and tailored to your specific project. 

No project is too small for us. We are here to help solve your problems and we see ourselves as your lab down the hall. 

We publish our own research:

SPR-pub-1

Kinetics of the multitasking high-affinity Win binding site of WDR5 in restricted and unrestricted conditions

Pub-3

Convergent Alterations of a Protein Hub Produce Divergent Effects within a Binding Site

pub_2

Interplay of Affinity and Surface Tethering in Protein Recognition

pub4

RPtag as an Orally Bioavailable, Hyperstable Epitope Tag and Generalizable Protein Binding Scaffold

We develop our own tools:

SPR

NSF SBIR Phase I Commercialization Grant:

NSF Award # 2129469 via Ichor portfolio company, Auctus Biologics, Inc.

Development of an Optical Biosensor to Facilitate Screening, Validation, and Development of Novel Drugs and their Biological Targets