Targeted Therapeutics Development

Solutions for breakthrough targeted therapeutics exploration

To keep your targeted therapeutics moving through the development process, you need to be able to make decisions with confidence, and without hesitation or costly delays. Whether you’re characterizing a signaling pathway or validating a therapeutic candidate, confident decisions begin with exceptional data.

pathway

From academic discovery through preclinical validation

Get the answers you depend on to keep the development process moving forward. Odyssey® Imagers and Pearl® Trilogy Small Animal Imagers deliver superior data for robust, replicable results you can rely on.

IRDye® Reagents are optimized for use with Odyssey Imagers and the Pearl Trilogy Imagers to provide an additional layer of certainty.

Enhanced understanding for improved target selection

Characterize your cell signaling pathways with confidence using quantitative, near-infrared (NIR) Western blots performed on an Odyssey Fc or Odyssey CLx Imager and quantitative, NIR In-Cell Western™ or On-Cell Western assays performed on an Odyssey CLx. Gain a fuller understanding of the details of your ligands, targets, pathways, and cellular effects.

Identify biomarkers and characterize leads

Quickly screen targets and identify potential therapeutic leads against specific pathways with DigiWest® Protein Profiling Services. Then, perform cell signaling assays on the Odyssey CLx.

Assess lead effects in organisms

Assess your therapeutic agent’s performance in vitro and ex vivo using the Odyssey CLx Imager or in vivo and ex vivo using the Pearl Trilogy Small Animal Imager. Decide which of your candidates appears most promising and move to the next step of validation.

Cell signaling assays

Understand more about your targets, pathways, and the effects your therapeutic has when you perform cell signaling assays on an Odyssey CLx Imager.

Trust your quantitative Western blots, In-Cell Western assays, and On-Cell Western assays to give you the most reliable results when you use an Odyssey CLx Imager and IRDye Reagents.

Characterize dose response with IC50 assays

Use the IC50 assay with the Odyssey CLx and IRDye Reagents to find the concentration of an inhibitor required to reduce a response by half. Get the data you need to continue through discovery and development.

Odyssey CLx

Determining IC50 by In-Cell Western Assay imaged on an Odyssey CLx Imager

PTK6 is abnormally expressed in breast cancers, and researchers have described kinase-dependent functions of PTK6 in driving tumor growth. As with any therapeutic approach, using small molecule inhibitors to target PTK6 activity requires validation of specificity and efficacy.

Example Study:Small molecule inhibitors reveal PTK6 kinase is not an oncogenic driver in breast cancers” Research conducted by Qiu, L., et al, Pfizer, PLoS One.1
PTk6 inhibitor

Inhibition of tumor cell growth by PTK6 inhibitors is independent of PTK6 kinase activity inhibition, providing evidence against using PTK6 kinase inhibition as a therapeutic strategy for breast cancer treatment. In-Cell Western Assays imaged on an Odyssey CLx Imager were used to assess cellular levels of PTK6 autophosphorylation normalized to cell number (measured by CellTag 700 Stain). Adapted from Qiu, L., et al.

Get a head start with high-content protein profiling

With DigiWest® Protein Profiling Services offered by NMI TT Pharmaservices through LI-COR, you can rapidly screen over 1,000 prevalidated antibodies against 50+ predefined signaling pathways. This will quickly narrow down your targets for further characterization against your therapeutic and for examination using an In-Cell Western Assay or Western blot.

DigiWest logo
step 1

Proteins are size separated via SDS-PAGE.

step 2

Proteins are transferred to a blotting membrane and biotinylated.

step 3

Sample lanes are cut into 96 strips to generate 96 molecular weight fractions immobilized on membrane.

step 4

Proteins are eluted into 96-well plates.

step 5

Biotinylated proteins are immobilized on the surface of Neutravidin-coated Luminex beads. One distinct bead set is added to each of the 96 wells, which results in a collection of distinguishable protein-loaded bead sets from a single sample.

step 6

Beads are pooled to reconstruct the initial sample lane where a defined color code correlates with each molecular weight of the immobilized proteins.

step 7

Immunoassay: a small aliquot of the bead pool is incubated with Western blot antibodies overnight before Phycoerythrin-labeled secondary antibodies are added for signal generation.

step 8

The sample is detected on a Luminex FLEXMAP 3D® instrument.

step 9

DigiWest® profile of protein analytes is generated.

Validation solutions

From advanced analysis of vetted therapeutic leads to small animal, tissue, and organ imaging, we offer solutions to help you understand the key characteristics of your therapeutic before moving to the clinic.

The Odyssey CLx Imager and the Pearl Trilogy Small Animal Imager provide an ideal combination to assess therapeutic delivery with NIR fluorescence and for complete analysis of your therapeutic agent’s performance.

The therapeutic agents tagged with IRDye Reagents deliver a clear image for detection and quantification. Validate your therapeutics and probes in vitro and ex vivo with the Odyssey CLx or in vivo and ex vivo with the Pearl Trilogy Small Animal Imager.

Pearl Trilogy Small Animal Imager

Assessing biodistribution of an siRNA delivery system for a promising cancer treatment using the Pearl Trilogy Imager

Ovarian and uterine cancers are often diagnosed at advanced stages, underscoring the need to identify therapeutic targets and means of delivering therapies to tumors. One promising therapeutic target is the AXL protein, which is involved in ovarian and uterine cancer metastasis. One potential treatment option is to silence AXL expression with siRNA, but a mechanism is needed to deliver the siRNA to the tumor.

Example Study:p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts” Research conducted by Mills, K.A., et al, Washington University School of Medicine, Scientific Reports.2
p5RHH-siRNA
p5RHH-siRNA nanoparticles were found to localize to tumor cells in vivo.To determine localization of p5RHH nanoparticles and to identify the best delivery method, mice bearing either uterine or ovarian cancer tumors were injected either intraperitoneally (IP) or intravenously (IV) with p5RHH-siControl nanoparticles labeled with a fluorescent probe. Excised tumors from IP-injected mice showed more probe localization than those from IV-injected mice. Live mouse and whole organ images were acquired on a Pearl Trilogy Imager. Adapted from Mills, K.A., et al.
probe development in vitro

In vitro analysis of plate-based assays

Characterize and validate the specificity, binding affinity, and other parameters of your therapeutic agents with the In-Cell Western or On-Cell Western assay performed on the Odyssey CLx Imager. Get the confidence you need in your agents before moving forward with small animal and tissue section imaging.

probe development in vivo

In vivo animal imaging with the Pearl Small Animal Imager

Capture a detailed representation of the in vivo molecular activity of your therapeutic agents in live animals. Assess uptake, clearance, and other key factors for development.

probe development ex vivo

Ex vivo tissue and organ analysis

Use an Odyssey CLx or Pearl Trilogy Imager to quantify the presence of dye-tagged probes in excised tissue or organ samples to assess the biodistribution, clearance, and other parameters of your therapeutic leads.

Consistency and speed without compromise

From academic discovery to pre-clinical validation, LI-COR has the products, tools, and services to let you make critical decisions with confidence.

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References

  1. Qiu, L., Levine, K., Gajiwala, K.S., Cronin, C.N., Nagata, A., Johnson, E., et al. (2018) Small molecule inhibitors reveal PTK6 kinase is not an oncogenic driver in breast cancers. PLoS ONE. 13(6). e0198374. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991704/
  2. Mills, K.A., Quinn, J.M., Roach, S.T., Palisoul, M., Nguyen, M., Noia, H., Guo, L., Fazal, J., Mutch, D.G., Wickline, S.A., Pan, H., Fuh, K.C. (2019) p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts. Sci Rep. 9. 4762. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423014/

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