Renewed pharma interest in GPCR biology and radioligand therapies is drawing attention to functional peptide screening platforms.
In a crowded AI drug discovery market, functional peptide screening could be a real differentiator. G protein-coupled receptors (GPCRs) and radiopharmaceutical targets are a hot area for investigation.
Recent scientific literature indicates that high-throughput GPCR-activating peptide screening is a timely technical topic. Big Pharma has also latched onto the trend: as one example, Eli Lilly inked a $140 million upfront payment to Radionetics Oncology, with the exclusive future right to acquire the biotech for $1 billion, in July 2024. The deal gave Eli Lilly “access to novel GPCR targets,” according to a press release.
CROs are also engaged in functional screening, especially for GPCR agonists, and peptide-mediated targeting, such as radioligand therapies.
GPCR/radiopharma and other targets
GPCRs are hot because they are biologically central: they sit on cell membranes, control signaling and already account for a large share of approved drug targets, so pharma knows they are druggable.
At the same time, many GPCRs remain underexplored, especially orphan receptors, leaving a discovery opportunity for new ligands and new mechanisms.
A ligand is a molecule that binds to the GPCR receptor and radiopharma uses that ligand as the targeting part of a radioactive drug.
As BioSpace previously reported, radiotherapeutics is a field that is ripe for exploration, with enormous potential due to the multiplicity of cancer surface targets to be addressed with different carriers, isotopes and formulation methods.
“GPCRs have always been a major focus for drug discovery, and even more so with the advent of drugs targeting GLP-1R and other incretin receptors,” says Simon Bushell, External Innovation and Business Development lead at Orbit Discovery. These molecules target receptors such as the glucagon-like peptide-1 receptor (GLP-1R), which is a class B GPCR and relevant in the treatment of metabolic diseases.
Biotechs targeting GPCR include Septerna, Structure Therapeutics and Escient Pharmaceuticals.
Orbit has partnered with a range of emerging biotechs and Big Pharma to identify new peptides which are involved in modulating inflammation and developing targeting peptides to direct treatments to specific cancers and across the blood-brain barrier, Bushell added. In addition, its discovery platform identifies new, highly differentiated peptides as treatments for pain relief and other neurological conditions.
Functional screening platforms
Orbit is not alone in the GPCR discovery market. Other service providers include Charnwood Discovery, Creative Bioarray and Creative Biogene.
The global peptide library screening services market is poised for significant growth and aimed and was projected to reach $50 billion last year. “Peptide libraries offer a powerful tool for identifying lead compounds with therapeutic potential, enabling researchers to screen vast numbers of peptides efficiently,” according to a Data Insights market report. “The continuous innovation in peptide synthesis and high-throughput screening platforms also plays a crucial role in expanding the capabilities and applications of these services.”
Orbit’s discovery platform screens very large peptide libraries directly against cells and uses functional readouts to identify novel agonists that activate signaling pathways.
Most peptide screening methodologies focus strictly on target binding as a readout. While this is beneficial for finding targeting peptides for therapeutic delivery, or for inhibiting protein-protein interactions, it is difficult for these approaches to find peptide agonists: peptides which not only bind a target, but which can also induce the conformational changes necessary to activate it, Bushell said.
Functional peptide screening — especially for GPCR agonists and peptide ligands for radioligand therapies — gives pharma the accurate hits it needs to derisk programs and speed translation, making these platforms a sensible differentiator in an otherwise crowded AI‑drug discovery landscape.
