Arrestin developments

FREMONT, Calif.—DiscoveRx Corp. kicked off the month ofOctober with an announcement that it had signed a global agreement with UnitedKingdom-based pharma giant GlaxoSmithKline (GSK) to provide access to itsPathHunter β-Arrestin parental cell lines, clones and associated reagents foruse in GSK's internal G-protein-coupled receptor (GPCR) screening and profilingefforts.

DiscoveRx framed the deal, along with what it calls "similarones signed with other major drug discovery organizations," as being one that"further validates PathHunter ß-Arrestin as a key platform to study GPCRbiology."

The Oct. 1 deal carries some special weight, though, giventhe size and stature of the entity involved, and Sailaja Kuchibhatla, seniorvice president of business development at DiscoveRx, says, "The GSK globalagreement vouches that the platform is a must and hence all sites on aworldwide basis have adopted the platform."

It's a deal that also comes hot on the heels of another one,announced just eight days earlier, with GSK and the UK's Medical ResearchCouncil Technology (MRCT), forming a three-way alliance to seek out naturalsubstances that bind to GPCRs.

Through the identification of the natural ligands for thesereceptors, the partners anticipate that this work will identify and validatenew drug targets that could ultimately help develop new therapies, as compoundsthat modulate GPCRs are already the basis of many licensed medicines.

That earlier deal, Kuchibhatla says, points to the value ofPathHunter b-Arrestin specifically for GSK's de-orphanization campaign ratherthan GPCR work in general, but notes that it "is a precedence setting dealwhereby a leading academic institute, a biotech tool company such as DiscoveRxand a premier pharma company have struck a strategic collaboration to discovernovel drugs," she says, adding: "DiscoveRx continues to innovate in field ofGPCR and kinase drug discovery with industry-leading cell-based assay platformsfor screening and profiling."

In the three-way collaboration, the parties note that thehuman genome encodes roughly 350 GPCRs, which respond to ligands, such ashormones, growth factors and proteins. Despite intensive efforts, though, theynotes that there remain at least 100 orphan GPCRs—receptors that have no knownligand or function.

Identifying the ligands and roles of these orphan GPCRscould potentially open up new areas of biology for therapeutic intervention anddrug discovery, Kuchibhatla notes, and this industrial/academic collaborationformed in late September will use the PathHunter β-Arrestin assay technology onwhat DiscoveRx calls "an unprecedented scale" to identify the ligands for someof these orphan GPCRs.

DiscoveRx is no stranger to the area of orphan GPCRs. Alongwith more than 140 known GPCR targets, it also offers 90 orphan GPCR assays forGPCR drug discovery.

After the three parties identify some of the ligands forthese orphan GPCRs, certain receptors will progress into high-throughputcompound screens, which could be performed either by MRCT or GSK, to identifylead molecules for possible drug discovery and development efforts.

In general, though, as GSK has had significant success atpairing orphan GPCRs with ligands, it will provide the GPCR ligand banks, laboratoryequipment and laboratory space. DiscoveRx, for its part, is providing access tostable cell lines expressing orphan GPCRs formatted in the PathHunterβ-Arrestin assay. And MRCT is in place to provide scientific staff members whocan perform project activities and identify academic collaborators tocharacterize ligand-matched GPCRs.

As Dr. Pyare Khanna, CEO of DiscoveRx noted with the releaseof the PathHunter β-Arrestin assay just over three years ago, "[This assay] isanother revolutionary offering from DiscoveRx which further confirms ourcommitment to provide novel, chemiluminescent assays for both biochemical andcell-based drug discovery research and screening. This product was developed inresponse to a market demand for a non-imaging, HTS technology for studyingvirtually any GPCR. With a product portfolio that includes Beta-Arrestintechnology, HitHunter cAMP assays, HitHunter IP3 assays, Calcium NW andCoelenterazine reagents, DiscoveRx is the only GPCR assay provider that offersbest-in-class screening solutions for every major type of GPCR target."

In other recent PathHunter β-Arrestin assay news, DiscoveRxannounced just a week after the global access deal with GSK that it had signeda co-marketing agreement that allows BioFocus to perform screening on behalf ofBioFocus' customers using DiscoveRx PathHunter β-Arrestin GPCR screening assay,HitHunter cAMP assays and associated cell lines.