A ligand is a substance that forms a complex with a biomolecule, often expressed in the cellular membranes such as G-protein coupled receptors (GPCRs). The introduction of membrane ligand binding assays and high-throughput screening (HTS) has revolutionized drug discovery. Ligand binding assays allow us to understand how a ligand or a novel synthetic compound interacts with a target protein and to measure the force (affinity) and speed (kinetics) of the interactions, while HTS helps automate research and reduce development time.
Because GPCRs are so prolific in the human genome, most modern drugs use GPCRs as targets. Changes in cell membrane and membrane itself control cell signaling and ligand binding in GPCRs. This is important pharmacology because it gives drugs a way to identify, target, and affect specific GPCR proteins.
Low-caliber membranes may respond in different ways from what would reflect your target’s true native pharmacology. Such membranes prepared from non-clonal heterogeneous pools of cells, or low-expressing native tissues, or cells expressing heavily engineered receptors will likely all have poor quality due to unreliable expression level, low-specific receptor binding by the ligand, and altered receptor pharmacology. This not only could cause inaccurate test results but also lead to added time spent on HTS.
1. High GPCR-target specific activity
2. Low lot-to-lot variation by generating from MULTISCREEN™ GPCR stable cell lines
3. Reliable, fast turnaround time from order to delivery, generally 1 month or less
4. Each batch QC’ed by cell surface expression or function
5. Available in both human and ortholog GPCR targets
MULTISCREEN™ GPCR membranes are offered at 1 mg, 5 mg, 10 mg, 100 mg, 500 mg, and 1000 mg quantities. 1 mg to 10 mg is typically purchased for initial assay development, followed by higher quantity orders custom-prepared for HTS or repeat orders to support hit-to-lead and lead optimization. With MULTISCREEN™ GPCR stable cell lines ready to go, our maximum turnaround time is generally 1 month, with smaller quantities of membranes delivered even faster. Customers of MULTISCREEN™ GPCR membranes never have to worry about any extended delays, as they would often experience elsewhere.
Multispan’s GPCR membranes are prepared directly from our catalog of over 500 functionally well-validated MULTISCREEN™ GPCR stable cell lines. These membranes can be used in primary screens for the human GPCR target, or counterscreens against closely related GPCRs and ortholog GPCRs from rhesus monkey, cynomolgus monkey, dog, ferret, rabbit, rat, and mouse etc. The ortholog targets in MULTISCREEN™ GPCR stable cell lines are generally expression and pharmacology-matched to their human counterparts.
In the event, your target is missing, we can custom produce it for you. We encourage you to take a look at our informational posters for detailed data sets. For example, the poster: “All Functional Assay in One Cell Line for Studying Signaling Bias”, described high quality membrane preps derived from MULTISCREEN™ stable cell lines expressing MOR and KOR were successfully used in both radioligand binding and GTPgamma-S assays. Another example Development of Radioligand Binding Assays for Compound Screening shows how membrane preps from MULTISCREEN™ GPCR stable cell lines expressing mGluR2 and mGluR3 receptors successfully worked in both radioligand binding and GTPgamma-S assays.