Cell-based kinase assays in HTS Benjamin Bader

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• Introduction • General considerations cell-based kinase assays • EFC-assays for Tyr-Kinases • TR-FRET systems: HTRF and Lanthascreen assays for the PI3K / Akt / mTOR pathway • Summary & conclusions 2 HTRF-symposium 2013 21 2
Kinases as drug targets cAbl and Gleevec (Noble 2004) (Fabbro 2012) recent additions Vandetanib VEGFR, EGFR, RET thyroid AstraZeneca Vemurafenib B-RafV600E melanoma Roche/Plexxikon Regorafenib multiKinase colorectal Bayer Critozinib ALK, ROS1 NSCLC Pfizer Bosutinib BCR/Abl CLL Pfizer Ruxolitinib JAK1/2 Myelofibrose Incyte/Novartis • human kinome: 518 protein kinases + 20 lipid kinases (Manning 2002) • currently, ~150 kinase targeted drugs are in clincal development (Fabbro 2012) • most registered kinase drugs target Tyrosine kinases, with more Ser/Thr kinase targetd drugs in the pipeline • most kinase drugs target the ATP-pocket • main indication: oncology 3 HTRF-symposium 2013 31 3
Page 1: Cell-based kinase assays in HTS Pot
Page 5 and 6: Features of a typical early kinase
Page 7 and 8: General options for cell-based kina
Page 9 and 10: TR-FRET systems: HTRF and Lanthascr
Page 11 and 12: Introducing the PI3K / Akt / mTOR p
Page 13 and 14: Lanthascreen Assay Development BacM
Page 15 and 16: Lanthascreen - virus efficiency 30%
Page 17 and 18: Lanthascreen - optimization • sti
Page 19 and 20: Lanthascreen - inhibitor validation
Page 21 and 22: HTRF - cell lines 18000 Ratio 16000
Page 23 and 24: HTRF - pathway inhibitor validation
Page 25 and 26: Focussed medium throughput screen 2
Page 27 and 28: Focussed medium throughput screen L
Page 29 and 30: Acknowledgements Anja Kretzschmar S

Cell-based kinase assays in HTS Benjamin Bader

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