Case Study

GSK:
Reducing reagent usage in PROTAC safety assay development

How GSK used DOE to develop a PROTAC safety assay and reduced assay running costs by 75%.

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At a glance

75% reduction in running costs
4-fold reduction in reagent usage
Entire assay optimization on one 384-well plate

CHALLENGES

Confirming a drug class is safe, without slowing down development.

PROTACs are an emerging class of small molecule drugs that enable selective degradation of proteins inside the cell by recruiting E3 ligases. GSK's PROTACs were initially classified in a high occupational hazard category with strict exposure limits. However, there was growing evidence that GSK's PROTACs didn't require this strict classification, and a robust safety assay was needed to validate this.

Traditional one-factor-at-a-time assay development is slow, reagent-heavy, and blind to how factors interact with each other. GSK needed a faster and more effective approach to develop a rigorous safety assay with minimal reagent usage.

GSK Protac case study slides - 4_3 format (4)

SOLUTION

DOE to develop a precise, low-consumption safety assay

The aim for GSK's Discovery Biology & Screening team was to use Design of Experiments (DOE) to find the minimum reagent concentrations needed for a luminescence signal within the signal window.

They created a space-filling DOE design in Synthace, to test a broad range of conditions covering the experimental space evenly. This meant they could vary the concentrations of multiple reagents simultaneously.

Synthace automatically translated the design into dispense instructions for the SPT LabTech dragonfly®, enabling seamless execution across 96 conditions in a single 384-well plate.

GSK Protac case study slides - 4_3 format (6)

Results

A validated safety assay, 4x cheaper to run, and evidence for reclassification

The DOE analysis revealed that a reliable signal could be generated using LgBiT and substrate concentrations four-fold lower than kit recommendations, and at PROTAC concentrations 100-fold lower than original conditions. This cuts running costs by 75%.

Importantly, the assay confirmed that GSK’s PROTACs do not degrade four safety critical proteins, providing compelling evidence to support reclassification to a lower occupational hazard category.

GSK Protac case study slides - 4_3 format (3)

“75% fewer experiments were used compared to OFAT.”

Khawthar Aumeer
Discovery Biology & Screening, GSK