BellBrook Labs Launches Transcreener cGAS Activity Assay to Accelerate Drug Discovery

The newTranscreenercGAMPcGASAssay directly measures the productcGAMP, in acGASenzymatic reaction allowing researchers to screen vast compound libraries for modulators of the enzyme. The assay will be used to discover and develop new treatments for autoimmune diseases and cancer by strategically targeting thecGAS-STING pathway.

Jan 9, 2019
BellBrook Labs

Researchers atBellBrookLabs have developed a high throughput screening (HTS) compatible biochemical assay to discover and advance small molecule modulators for the target cyclic GMP-AMP synthase (cGAS).TheTranscreenercGAMPcGASAssay directly detects cyclic GMP-AMP (cGAMP), the product of acGASreaction, allowing researchers to monitorcGASactivity with simple, mix-and-read fluorescent detection.

The presence of DNA in the cytosol of eukaryotic cells is an indicator of infection or cellular damage, and it elicits a strong innate immune response.cGAStriggers this response to cytoplasmic DNA by producing the dinucleotide second messengercGAMP, which activates the stimulator of interferon genes (STING) receptor leading to a type I interferon response. Recent studies suggest thecGAS-STING pathway is a promising area for therapeutics targeting autoimmune disease and cancer.

TheTranscreenercGAMPcGASAssayis a competitive immunoassay that uses a highly specific antibody forcGAMPand a fluorescent tracer.cGAMPdisplaces the tracer from the antibody resulting in a robust fluorescent polarization (FP) readout. Along with basiccGASresearch including enzymology and regulation, the new assay is designed for miniaturized 384 or 1536 well formats, perfect for HTS. It also has great utility for SAR and follow-up studies, providing accurate dose-response measurements, mechanism of action studies, and determination of inhibitor residence times using jump-dilution kinetics.

Based on the provenTranscreenerplatform, trusted for over 10 years by pharmaceutical companies around the globe, the assay has been extensively validated for HTS, SAR, and MOA studies with human and mousecGASinBellBrook'sinternal discovery program. Combining results from biochemical screening withaccuratevalidation in cellular assays will accelerate the discovery of potent modulators of the enzyme, leading to new potential treatments for disease.

About BellBrook Labs:

BellBrook Labs is dedicated to accelerating drug discovery and biological research by providing innovative high throughput screening solutions. BellBrook’s core technology Transcreener is a universal, homogenous biochemical assay platform based on detection of nucleotides that makes it easy to screen thousands of different enzymes. These include validated targets like kinases, as well as emerging targets like ATPases, GTPases, methyltransferases, and glycosyltransferases. Detection reagents from BellBrook Labs help researchers progress toward more effective therapies for cancer and other debilitating diseases.