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

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<strong>IonWorks</strong> can resolve differential pharmacology1 st Pulse Compound Concentration Response25 th Pulse Compound Concentration Response10010080Compound 1Compound 280Compound 1Compound 26060% Inhibition40200IC 50= 0.569µMIC 50= 121µM% Inhibition40200IC 50= 0.148µMIC 50= 50µM-20-20-400.01 0.1 1 10 100 1000Concentration (µM)0.01 0.1 1 10 100 1000 10000Concentration (µM)Two compounds with differential pharmacology, but similar use-dependency ratiosCompound 1 use-dependence ratio is 3.8Compound 2 use-dependence ratio is 2.5
Assay validation post-relocation• Run Patch Plate Tests– Verify overall operationalcapability• Run basic cell plates– Verify seal rates, sealvalues and current are onpar• Run protocol withreference agents– Verify IC 50 values haven’tdrifted
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: Sample ion channel recordingPre-com
Page 19 and 20: Resolution approachRe-chlorideE-hea
Page 21 and 22: I-V and inactivation curvesre-visit
Page 23 and 24: Pre- to post-addition current ampli
Page 25 and 26: Summary• Cell line husbandry and
Page 27 and 28: Back-up slides
Page 29 and 30: Kv70Single hole mode70Population pa

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