Integrated Drug Discovery




On occasion our partners have multiple GPCR targets of interest each with varying levels of validation and scientific rationale. To streamline the drug discovery effort and optimize resources, we typically suggest a systematic target vetting approach.

GPCR Target Pool


A select number of targets, ideally no less than 3, typically proposed by our partner and on occasion suggested by Beacon are designated as a target pool of exclusivity, and the focus of the collaboration. This pool may be expanded, exchanged or reduced to provide full flexibility to our partners and their research priorities. To avoid conflicts of interest, Beacon will not work on any single target with more than one collaborator at a time. 


As part of the vetting process Beacon scientists will perform an initial interrogation of the target pool and prioritize pool receptors based upon consideration of:

1. Data in the scientific literature

2. Beacon and/or partner proprietary data if available 

3. Beacon's history with each target

4. Partner's internal discovery priorities

As target evaluation is completed, targets that are prioritized will progress through GPCR target incubation process. 

GPCR Incubation

Early target validation presents a major challenge to most drug discovery organizations. Literature reports provide numerous novel ideas but data are often not reproducible and internal bandwidth to evaluate these ideas is often very limited. The Beacon team has spent almost 20 years interrogating novel targets in the GPCR space, we leverage our experience to interrogate multiple GPCR targets and prioritize those with robust, reproducible data for assay development and high throughput screening. We will tailor a research plan to the targets included in the collaboration. Our goal is to generate sufficient evidence to compel initiation of a drug discovery campaign or to decisively eliminate targets from consideration.
Validation is particularly important when working with orphan GPCRs. These GPCRs are sometimes challenging, as the native ligand is unknown making it very difficult to set up meaningful assays, as signaling and putative biology is often poorly characterized. We fully recognize that literature findings are often problematic, indeed, most GPCR deorphanization reports are not reproducible, researchers often utilize poorly characterized pharmacological tools, and the resulting biological findings are often erroneous. 

Target Validation Activities

A specific validation plan will be designed in collaboration with the partner, however such a program typically includes the following activities for each receptor:

1. Comprehensive literature summary

2. Target expression profiling for human receptor and its rodent ortholog

i.  Summarize data from internal and public databases
ii. Evaluate expression in key target tissues (normal/disease state)

3. Summarize/generate evidence to support the receptor's therapeutic utility

i.  Human GWAS and SNP data 
ii. Rodent KO and transgenic data

4. Evaluate potential on/off target liabilities

i.  Expression profiling in key tissues associated with side effects

5. Identify and replicate key in vitro and in vivo data

i.  Synthesize tool compounds from literature and confirm literature findings
ii. Extend findings with additional studies to support internally generated hypotheses

6. Confirm drug discovery effort feasibility

i.  Initiate assay development
ii. Explore HTS campaign feasibility

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