Domain Therapeutics NA (DTNA) Inc. specializes in G Protein-Coupled Receptor (GPCR) and Receptor Tyrosine Kinase (RTK) signaling and function. Our BRET-based bioSensAllTM biosensor technology allows for detailed and broad-spectrum signaling profiling of GPCRs, RTKs and their ligands, while leaving these receptors untagged. This technology revolves primarily around the real-time monitoring of receptor proximal events immediately linked to the transmembrane receptor activity, namely heterotrimeric G protein activation and β-arrestin coupling for the GPCRs, and recruitment of SH2-domain proteins for the RTKs.
The GPCR assay brings the unique capacity to quantify the engagement of 14 distinct heterotrimeric G protein subtypes as well as both non-visual β-arrestin isoforms.
The RTK assay gives the possibility to follow the recruitment of various SH2-domain proteins and study the complete trafficking of these receptors.
Both assays provide a complete and detailed fingerprint of any GPCR / RTK ligand and allow to study the impact of receptor mutations on their signaling. This data is particularly valuable in a screen / early drug development program to select and optimally design your lead compound.
Our bioSensAllTM platform is applicable to the study of agonists (including inverse agonists), antagonists and allosteric modulators and is ideally suited for the identification of biased ligands. The assay is homogenous, does not require receptor modification and is performed in living cells, thus allowing for real-time analysis of signaling kinetics and dynamics. We approach each project with an “agile” philosophy. After consultation with our staff scientists, a draft project proposal tailored to the client’s needs is rapidly (within 24h) generated and returned to the client for review. Upon mutual finalization of the service proposal, we are ready to begin the project. Our streamlined procedure ensures delivery of the highest quality data in the shortest possible timeframe, with an average project turnaround time of one month. We remain available for discussion during and after completion of the work. As a company, DTNA strives to build close professional partnerships founded on confidence, transparency and confidentiality. We strongly believe in working collaboratively with, and not simply for, our partners and clients in addressing their needs and achieving their objectives. At DTNA, we are not simply service providers; rather, we consider ourselves as dedicated partners in your research and drug discovery endeavors.
Functional assays allowing to study the proximal signaling pathways and complete trafficking of the following Receptor tyrosine kinases (RTKs): EGFR, VEGFR, EGFR, PDGFR and Trk.
We use SH2 domain biosensors allowing to study the signaling of RTK receptors while leaving the receptor untagged. The data generated by the assay is particularly relevant to screen and improve the early drug development phases to generate an optimal lead candidate. Other RTK assays can be developed on demand.
Functional assay which has the unique capacity to quantify in real-time the engagement of 14 distinct heterotrimeric G protein subtypes as well as both non-visual β-arrestin isoforms, while leaving the receptor untagged.
The data generated by this assay is particularly relevant to screen and improve the early drug development phases to generate an optimal lead candidate.
Typical projects are aimed at assessing and/or comparing the global signaling profile of one or more target GPCRs, including receptor variants, subtypes, isoforms and orthologues. A restricted number of ligands (usually ≤ 5) are tested using a panel of 12 biosensors for the signaling events directly associated with GPCR activity (i.e., heterotrimeric G protein biosensors for the activation of Gαs, Gαq, Gα11, Gα14, Gα15, Gαi, GαoB, Gαz, Gα12 or Gα13; sensors for the engagement of β-arrestin 1 or β-arrestin 2). This panel of biosensors can be complemented with those measuring more receptor-distal signaling events (i.e., generation of second messengers including cAMP, DAG, PIP3; PKC and RhoA activation; Gßɣ activity). The latter distal biosensors can also serve to confirm data previously generated by clients using other technologies. These projects expose new users to the power of bioSensAllTM technology and allow them to evaluate our platform.
Ligand profiling services can be divided into small and large campaigns. Profiling can be performed on a minimum of 2 biosensors to analyze for signaling bias. Alternatively, a more global profiling with a broader set of biosensors can be conducted and the data ultimately used for classifying compounds into signaling clusters. We offer analysis of bias and compound clustering at an affordable cost.
As an extension of our ligand profiling services, compounds can also be counter-screened for selectivity against target GPCR subtypes, isoforms and/or orthologues. Counter-screens can be conducted using any number of biosensors.
The sky is truly the limit with bioSensAllTM technology. The extensive experience of our staff scientists in the development of BRET-based assays makes it possible to address numerous questions regarding the function, localization and/or activity of your target of interest. Following stringent validation, all newly developed assays can be performed at DTNA, or can be out-licensed exclusively to the client.
Our bioSensAllTM assay is compatible with 96-well and 384-well formats, thus permitting for HTS campaigns. Please contact us to discuss your specific screening needs.
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