â Realizing the potential of IonWorks screening in a drug discovery ...

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Where we go from here…• Is this a cell line and/or hardware issue?– Assess alternate Na v cell line–Na v cell line on alternate platform– 12 vs. 48 channel dispense head?• Does a PPC mode assay reduce variability?• Re-clone cell line in CHO background• Shorten pulse train length and frequency• Continue to liaise with MDC
Summary• Cell line husbandry and detailed characterization ofgrowth parameters are critical to maximizing success• IonWorks is an integral part of a coordinated ionchannel drug discovery paradigm– Rapid SAR analysis and compound attrition– Ability to support high-speed chemistry approaches– Additive and complementary to optical approaches• Functional pharmacological data can be obtainedrapidly to aid in optimal candidate drug identification– Provides a means to identify compounds targeted to diseaserelevantion channel states
Page 1 and 2: Realizing the potential of IonWorks
Page 3 and 4: Groton ion channel drug discoveryCN
Page 5 and 6: Electrophysiology has an integralro
Page 7 and 8: Assessment of cell growth parameter
Page 9 and 10: Growth kinetics dictate experimenta
Page 11 and 12: Variables influencing assay success
Page 13 and 14: The importance of voltage control o
Page 15 and 16: Sample ion channel recordingPre-com
Page 17 and 18: Assay validation post-relocation•
Page 19 and 20: Resolution approachRe-chlorideE-hea
Page 21 and 22: I-V and inactivation curvesre-visit
Page 23: Pre- to post-addition current ampli
Page 27 and 28: Back-up slides
Page 29 and 30: Kv70Single hole mode70Population pa

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