Invitrogen said last week that it will acquire cell-based assay company Sentigen Holding for around $25.9 million in cash, significantly bolstering a relatively thin portfolio for GPCR screening and building on its kinase and ion channel drug screening products.
Invitrogen hopes it can boost sales of Sentigen’s relatively young and unproven Tango GPCR screening technology through its significant marketing muscle and by combining Tango with its popular GeneBLAzer reporter gene assay products.
Meanwhile, Invitrogen is betting that Sentigen’s Tango technology, as well as its division-arrested assay-ready cells, will help it grow its own assay-development business by providing an improved method for screening GPCRs and other “key” drug target classes, Nick Ecos, vice president and general manager of Invitrogen’s Discovery Sciences Business, said this week.
The acquisition “really provides us an entry into the GPCR target class market,” Ecos said. “But we’re going to market this as one of a number of solutions across target classes. Our strength in the Discovery Sciences business unit has traditionally been first of all in kinases, and also in nuclear receptors and ion channels.”
It may seem somewhat surprising that a molecular biology tools provider the size of Invitrogen had not yet offered highly dedicated products for GPCR screening. After all, GPCRs are among the most studied cellular drug targets, constituting anywhere from 30 percent to 50 percent of screening targets, depending on whom you ask. It is estimated that nearly 60 percent of all prescription drugs on the market owe their activity in whole or in part to GPCRs.
Furthermore, rivals such as Molecular Devices and PerkinElmer have been playing in the GPCR screening space for several years; and GE Healthcare recently boosted its presence in the market by signing an agreement to exclusively distribute DiscoverX's HitHunter cAMP enzyme fragment complementation-based assays worldwide.
Invitrogen’s popular GeneBLAzer assay technology can be customized to study GPCRs, but “the Tango technology enables quantitative biology on orphan targets and other difficult GPCR pathways that we can’t achieve alone using the GeneBLAzer reporter technology,” Ecos said. “We find that the use of Tango with GeneBLAzer actually makes the readouts of both a little bit better.”
In evaluating Sentigen, Invitrogen “observed that the Tango technology separates endogenous protein from background protein better than anything else on the market,” he added. “That separation enables the scientist to find ligands that they can’t find today, which is what makes an orphan target.”
As such, Invitrogen intends to fold certain elements of Tango and GeneBLAzer into a single offering. Tango has traditionally been used with a luciferase reporter construct, while GeneBLAzer is based on β-lactamase. Ecos said that Invitrogen’s internal research has shown that the readouts for a Tango assay are “simply better” when you use β-lactamase.
“We’ve reviewed the progress that Sentigen has made using the technology with luciferase, and since we’ve done it in both luciferase and GeneBLAzer internally, I think we can make some reasonable conclusions,” Ecos added. Despite this, he said, Invitrogen will also continue to offer the Tango assay with a luciferase reporter, as some scientists conducting GPCR screens may be more comfortable with that readout technology.
“The Tango technology enables quantitative biology on orphan targets and other difficult GPCR pathways that we can’t achieve alone using the GeneBLAzer reporter technology.”
Sentigen’s Tango assay technology can also measure protein-protein interactions in living cells, according to Invitrogen. Sentigen subsidiary Cell & Molecular Technologies launched the Tango GPCR assay platform one year ago.
According to CMT, the Tango platform comprises a panel of 54 GPCR targets. Key features of the platform include up to 1,700-fold signal-to-background ratios, high specificity, and broad applicability to novel targets, including orphan receptors, where the ligand of the receptor remains unknown and blends in with the background.
The assays can be run on standard plate readers and are not platform specific, according to Ecos.
Invitrogen is also very interested in incorporating Sentigen’s division-arrested assay-ready cells. These cells are designed to “uncouple” the process of cell production from cell-based drug screening, Ecos said.
“We’re interested in applying this not only to GPCR targets, but to all of our cell-based assays,” he said. “We believe that will help simplify life for our customers who, as they adopt the use of cell-based assays more and more, are finding that controlling the cell growth conditions can be quite a hassle.
“This will make it easier for customers because they can just plug these cells in,” Ecos added. “They’re still alive, but they’re no longer going to proliferate. So the conditions for doing the cell-based assays are more stable. The cells die after the assays are done, but that’s fine, because for the most part, customers really aren’t interested in maintaining these big cell culture installations.”
The size of Sentigen’s current customer base for either the Tango assay or division-arrested cells, which Invitrogen will be inheriting, is unclear. Calls to Sentigen were not returned in time for this publication. Ecos, however, said that Tango, at least, is “very new,” and does not yet have a widely established customer base.