Reaction Signals Q1 2026 Newsletter
Headlines In This Issue
Featured Research: Preclinical Models
Our novel approach maintains BBB integrity in preclinical brain tumor models, enabling more predictive assessment of CNS therapeutic penetration and efficacy.
Scientific Spotlight: GPCRs and LinkLight™ Technology
Complete GPCR characterization with LinkLight to detect β-arrestin and 14-3-3 recruitment. Insights into biased signaling, therapeutic durability, and tolerance mechanisms that cAMP and calcium assays alone cannot predict.
New at Reaction Biology
GxP potency testing for erythropoietin (EPO) in vitro cell-based assays and GLP receptor agonist obesity targets.
Important Dates
Compound submission deadlines for multiple screening panels plus upcoming conferences.
Featured Research
POSTER
Preserving Blood Brain Barrier in Preclinical Tumor Models
Many promising brain cancer therapies fail in clinical trials because preclinical brain tumor models do not provide an intact blood-brain barrier (BBB).
Tumor implantation disrupts BBB integrity in standard intracranial models, potentially causing false preclinical efficacy that can’t be translated in the clinic for patients with intact BBBs. While IV and intracardiac approaches preserve the BBB, they frequently result in widespread metastases and premature study termination.
Our intra-carotid implantation model offers a better path forward. This approach directs tumor cells specifically to the brain while maintaining BBB integrity, enabling more accurate assessment of BBB-penetrant therapeutics and their potential for clinical translation.
The data demonstrates consistent brain-targeted colonization with median survival of 30 days, providing a robust platform for evaluating BBB-penetrant therapeutics in both primary brain tumors and metastatic lesions.
Scientific Spotlight
G-Protein Coupled Receptors
GPCRs represent the largest family of cell surface receptors and are one of the most successful drug targets across all therapeutic areas. However, traditional screening approaches that focus solely on G-protein activation miss critical regulatory mechanisms that determine therapeutic durability, tolerance development, and side effect profiles.
While cAMP and calcium flux assays reveal G-protein mediated pathways, they do not capture the β-arrestin recruitment and 14-3-3 protein stabilization events as part of the complete signaling landscape.
This regulatory layer is crucial for understanding orphan targets, biased ligands, or transient protein-protein interactions.
WEBINAR
Cell-Based Functional Assays for GPCR Drug Discovery
Access our pre-recorded technical webinar by Associate Director, Yong Wan PhD, who explains the differences between various GPCR functional assays (β-arrestin recruitment, cAMP, calcium) and their applications in diverse signaling pathways (Gs, Gi, Gq coupling partners).
BROCHURE
Complete GPCR Characterization with LinkLight™
From pathway discovery to biased ligand profiling, explore how LinkLight complements our established GPCR portfolio to deliver comprehensive mechanistic insights.
- 90+ GPCR targets across all major receptor families (aminergic, peptide, lipid, nucleotide)
- Universal orphan receptor characterization when G-protein coupling is unknown
- Ligand bias quantification comparing activity ratios across regulatory vs. G-protein pathways
- Immediate, transcription-free readouts that capture transient signaling events
- Persistent signal enabling detection of fleeting protein-protein interactions
INDUSTRY INSIGHTS
The Evolution of GPCR Drug Discovery
Traditional GPCR drug development focused exclusively on agonism or antagonism at G-protein pathways, but emerging evidence demonstrates that β-arrestin-mediated signaling can produce distinct, and sometimes superior, therapeutic outcomes.
“Therapeutic Potential of Targeting β-Arrestin”
This review explores how β-arrestin-mediated signaling influences therapeutic outcomes across cardiovascular, metabolic, pain, and addiction indications. The authors demonstrate that biased ligands selectively activating G-protein or β-arrestin pathways can maintain efficacy while avoiding side effects, and that understanding β-arrestin recruitment is essential for predicting tolerance development and chronic dosing outcomes.
Frontiers in Pharmacology, 2019 →
“ERK and β-Arrestin Interaction: A Converging Point of Signaling”
Using LinkLight technology to measure ERK/β-arrestin complex formation across GPCRs, receptor tyrosine kinases, and cytokine receptors, the authors show that β-arrestin-mediated ERK activation produces distinct spatiotemporal dynamics compared to G-protein pathways—leading to different transcriptional outcomes that traditional endpoint assays cannot capture.
International Journal of Molecular Sciences, 2020→
“The Protean Nature of 14-3-3 Proteins in GPCR Signaling”
This study provides the first GPCRome-scale characterization of 14-3-3 protein interactions, screening 82 receptors across all seven human 14-3-3 isoforms using LinkLight technology. The findings reveal that GPCR-14-3-3 interactions are isoform-specific and ligand-modulated, with different isoform combinations producing varying functional outcomes including modulation of receptor surface expression, attenuation of G-protein dissociation, and enhanced β-arrestin recruitment.
ACS Pharmacology & Translational Science, 2025 →
What this means for your program: Traditional G-protein assays alone cannot predict tolerance development, chronic dosing efficacy, or pathway-specific side effects. LinkLight directly detects β-arrestin and 14-3-3 recruitment with persistent, transcription-free readouts—enabling comprehensive signaling profiles before costly in vivo studies
Product Highlights
GxP Potency Assays
Reaction Biology continues expansion of regulatory-grade assay capabilities with ICH Q2(R2)-qualified methodologies for batch release and stability testing:
- Erythropoietin (EPO) Potency: Cell-based alternative to Ph. Eur. in vivo mouse assays—3R-compliant and regulatory-ready
- Obesity Target Assays: Potency assay testing for GLP-1, GIP, and glucagon receptors supporting next-generation metabolic therapeutics
Upcoming Screening Schedule
Ensure your compounds are included in our upcoming screening runs.
Please note the following deadlines for sample submission.
Bromodomain Full Panel
January 30 | February 27 | April 3
Protease Full Panel
January 23 | February 20 | March 20 | April 24
Phosphodiesterase (PDE) Full Panel
January 23 | February 20 | March 20 | April 24
ProLiFiler™ Cancer Cell Panel
February 12 | April 2
Histone Deacetylase (HDAC) Full Panel
January 30 | February 27 | April 3
InVEST44 Safety Panel
February 6 | March 6 | April 10
Methyltransferase Full Panel
January 16, 30 | February 13, 27 | March 13 | April 3, 17
Kinase Panel Screening (US Facility):
Full Panel: January 14, 28 | February 11, 25 | March 11 | April 1, 15, 29
1 mM ATP (Wildtype, Mutant, Atypical, Lipid, and Diacylglycerol): January 21 | February 18 | March 18 | April 22
Diversify Panel: February 4 | March 4 | April 8
Kinase Panel Screening (German Facility)
Full Panel (Wild Type, Mutant, Diversify, Lipid): February 5 | March 5 | April 30
Conferences and Events
AACR IO
- Date & Location: February 18-21 | Los Angeles, CA
World ADC London
- Date & Location: February 23-26 | London, UK
Festival of Biologics US
- Date & Location: March 4-5 | San Diego, CA
Society of Toxicology
- Date & Location: March 22-25 | San Diego, CA
Biologics UK/TIDES (Next Gen Biomed)
- Date & Location: March 24-25 | London, UK
Tumor Model Nordics
- Date & Location: March 2026 | Stockholm, Sweden
Drug Discovery Chemistry
- Date & Location: April 13-16 | San Diego, CA
AACR
- Date & Location: April 17-22 | San Diego, CA
Annual GPCR-Targeted Drug Discovery Summit
- Date & Location: April 28-30 | Boston, MA
About Reaction Biology
Experts in Supporting Innovation
Reaction Biology specializes in answering your complex scientific questions to accelerate the development of your breakthrough therapeutic candidates. For over 20 years, leading pharmaceutical, academic, and biotech organizations worldwide have relied on our labs as the partner of choice to advance their most promising drug candidates and research pipelines.
Our track record speaks for itself: we’ve served over 2,000 clients across more than 5,000 projects every year. We act as an extension of your team and operate with the speed, precision, and scientific rigor that you demand to meet your critical research milestones.
With strategically located facilities in the US and EU, we provide streamlined operations, quick turnaround times, and secure handling of your most sensitive research materials.
Our broad discovery and development services portfolio spans capabilities from protein production to in vivo, backed by an expansive library of over 2,000 validated drug targets and 1,000+ cell lines. Our global, multidisciplinary experts deliver custom and tailored solutions with a demonstrated track record of success, including innovative therapies approved by the FDA and other global regulatory agencies.
