Assays
Figure 4: Reasons that have prevented or restricted current use of FLT technology 3.62
Insufficient in-house expertise in FLT assay development Cost of new instrumentation
Lack of suitable dyes (covering wide range of fluorescent lifetimes) Lack of relevant applications
Lack of standard toolbox reagents and dye derivatives Lack of publications validating technique
Lack of assay development services (by vendor) Lack of adequate software or algorithms Lack of custom labelling of assay reagents (by vendor) Perceived lack of vendor interest in FLT technology Lack of off-the-shelf assay kits Lack of suitable instrumentation
2.92 2.95
2.78 2.64 2.51
1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 Rating SCORE 1 to 5, where 1 = least important, and 5 = most important
© HTStec 2010 3.47
3.32 3.33
3.22 3.25
3.14
What would make an FLT-based kinase assay attractive?
When survey respondents were asked what would most compel them to consider an FLT-based kinase platform they ranked superior ability to deal with assay interference as the most compelling reason (Figure 5). What we think respondents are saying here is if FLT’s ability to deal with assay interfer- ence in kinase assays resulted in better assay qual- ity (ie better Z’ values than other assay technolo- gies) it would almost certainly trigger adoption by some screening groups. Other important criteria were price per well (data point) and then informa- tion rich output. All these three reasons match well with the strengths of the new FLT assay kit offer- ings described below (see Almac FLEXYTE®).
What might FLT displace? If FLT were successful in capturing a proportion of the kinase screening market share, where will it impact current screening technologies (Figure 6)? Survey feedback suggests that most respondents (28%) think TR-FRET (ie HTRF, LANCE, TR- IMAP, LanthaScreen) is the kinase platform/tech- nology most likely by to be displaced overall by an FLT-based kinase platform. This was followed by glow luminescence and then FP with ligand, (ie NO antibody). This finding is perhaps a little surpris- ing, as these happen to be the most used and most preferred kinase platforms today. This finding is probably suggestive of a degree of grudging accept- ance of these technologies, ie in the absence of bet- ter alternatives and no doubt sweetened by highly competitive price incentives.
Drug Discovery World Summer 2010
Figure 5. What would most compel respondents to consider a new flt-based kinase platform
Superior ability to deal with assay interference
Information rich output Price per well (data point)
Applicable to other targets eg proteases, lipid kinases, phosphatases
Generic protein kinase platform supported by preeminent research lab
Multiplexing capability
Avoids use of radioactivity and associated costs Concentration and volume independent Antibody free
No specialised secondary reagents required 7.28 6.80 6.08 5.64
5.30 5.45
5.05
4.84 4.86
4.59
1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 Ranking SCORE 1 to 10, where 1 = least compelling, and 10 = most compelling
10.00 © HTStec 2010
What are the prospects for the wider adoption of FLT?
Opinion on the future adoption of FLT into survey respondents workplaces (surveyed in 2007) suggests that FLT will remain a largely unimportant (0% tar- gets screened) or a low importance tool ((Figure 7). In the medium term (after 3 years, ie in 2010) sur- vey respondents were evenly split between no or low importance and medium or high importance. In the long term (after 5 years, ie by 2012) respondents’ expectations for FLT have risen considerable with
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