KinaseScreen - RapidKinase • Set panels of kinases assays - RapidKinase 48 with broad representation of the kinome Discovery Alliances & Services - RapidKinase 200 for wide kinase selectivity screens • Create your panel using any combination of plates • Relies on Caliper ProfilerPro plates reagents: - 24 kinase assays per ProfilerPro plate - Highly reproducible data - Assays run at apparent ATP Km

KinaseScreen CDAS| Programs

Kinases are an important class of enyzmes involved in signal transduction and signaling networks within cells. Kinase signal- ing pathways play a fundamental role in regulating cell prolif- eration, cell metabolism and cell death. Research shows that changes in protein kinase activity within a cell can lead to several disease states, most notably cancer. With this knowledge base, scientists have been investigating the ability of drugs to block various protein kinases as a cancer therapy. This approach has proved successful with the discovery of several kinase inhibitor drugs for the treatment of various cancers. These drugs include Gleevec®, Iressa® and Tarceva®. In addition to their involvement in cancer, protein kinases are implicated in diabetes, inflamma- tion and neurological development and degeneration.

Discovery Alliances & Services ©2010 Caliper Life Sciences, Inc. All rights reserved. Preclinical Contract Services Caliper, the Caliper logo, KinaseScreen, KinaseAdvisor, ProfilerPro, CDAS and Discovery 7170 Standard Drive Alliances & Services are tradenames and/or trademarks of Caliper Life Sciences, Inc. Hanover, Maryland 21076-1334 USA All other names are trademarks of their respective companies. Tel: 1.410.712.4410 / 1.800.543.4141 CDAS-BR-01 Nov 10 KinaseScreen Programs KinaseScreen Programs

Protein Kinases KinaseScreen Mechanism of Action (MoA) Protein kinases are involved in a wide variety of disease states and over 30% of all spending for drug development focuses on • Understand how compounds interact with enzymatic targets this area of research. Through the use of the Caliper LabChip technology platform, Caliper Discovery Alliances & Services has developed KinaseScreen – a complete platform of kinase services to assist researchers in accelerating their lead identification • Quickly identify allosteric inhibitors and ATP competitors and optimization efforts in this very important area. • Characterize ATP competitors’ mode of inhibition (Competitive, Non-competitive, Un-competitive) • Determine K-off values Kinase Selectivity - KinaseAdvisor • Turnaround time: 5 to 6 weeks • Customizable panels of assays and test conditions - Large panel of optimized off the shelf assays - Check our website for updates - Select drug test concentrations and replicates - Option for ATP concentration at Km or other value - Inhibition or Activation assay formats - Screen against active or inactive enzyme forms

TRKC TRKB • Fast data turnaround times FGFR2 TRKA FGFR3 MuSK FGFR1 FLT1 TK DDR2 FGFR4 ROR2 KDR - Support new compound synthesis and DDR1 Ret ROR1 EphA5 EphB1 FLT4 EphA3 EphB2 IGF1R Src Axl lead optimization chemistry programs InsR Fms/CSFR HER2 Yes EphA4 EphB3 Mer Kit EGFR EphA6 EphB4 IRR Tyro3/Sky Fyn FLT3 HER4 EphA7 Ros Ron Frg HER3 EphA8 ALK Met PDGFRα • Fully Optimized Assay Protocols EphA2 β BLK PDGFR Ack LTK RYK EphA1 Tnk1 Lck FRK TIE1 EphB6 KinaseAdvisor CCK4/PTK7 TIE2 Tyk2 HCK Srm EphA10 - Caliper LabChip technology JAK1 Lyn Brk

Fes FAK Lmr1 JAK2 ANKRD3 CTK SuRTK106 Fer PYK2 Lmr2 JAK3 SgK228 List of Kinase Assays CSK JAK3~b - Physiologically relevant peptide substrates Syk RIPK2 ERK1 JAK2~b Lmr3 ZAP70 IRAK1 RIPK3 ERK2 Arg Etk/BMX LIMK1 TKL JNK1 Tyk2~b ANPα MOS IRAK3 LIMK2 Abl (E255K) (h) DYRK2 (h) InsR (h) - Activation Mode PDK1 (h) Abl BTK RIPK1 JNK3 ERK5 WNK1 JAK1~b ANPβ - Direct and simultaneous detection p38γ MLK4 SgK496 IRAK2 MLK2 TXK WNK3 LRRK1 TEST1 YSK1 p38δ JNK2 NLK HSER TEC PBK IRAK4 LRRK2 TEST2 ILK MLK3 MST3 Abl (G250E) (h) EGFR (ErbB1) (h) IRAK4 (h) PI3Ka (p110a/p85a) (h) WNK2 KHS1 of substrate and product p38β ERK3 SCYL1 CYDG MKL1 Wee1B ITK MLKL ALK1 TAK1 DLK KHS2 MST4 p38α ERK4 WNK4 CYGF CDK2 CHED Wee1 SCYL3 ALK2 HH498 LZK Abl (h) EGFR (L858R) (h) Jak2 (h) Pim1 (h) GCK MST1 CDK3 CRK7 ERK7 NRBP2 SCYL2 SgK307 ALK4 CDK10 MYT1 KSR ZAK HPK1 MST2 NRBP1 SgK424 TGFβR1 BMPR1A - Ratiometric method CDC2/CDK1 PITSLRE CDK9 CDK11 BMPR1B KSR2 ARAF BRAF Abl (Q252H) (h) EGFR (L861Q) (h) Jak3 (h) Pim2 (h) ALK7 CDK5 CDK7 CCRK CDK8 RAF1 MISR2 STE TGFβR2 NIK TAO1 PFTAIRE2 CDK4 MAK SgK196 BMPR2 MYO3A Abl (T315I) (h) EGFR (T790M) (h) JNK2 (h) PKA (h) - Homogeneous assay format KIS TAO2 ActR2 PFTAIRE1 CDK6 ICK SgK493 PRPK GCN2~b MYO3B TTK Tpl2/COT ActR2B TAO3 HGK IRE1 PCTAIRE3 MOK SgK396 Haspin MINK Akt1 (PKBa) (h) EGFR (T790M/L858R) (h) KDR (VEGFR2, FLK1) (h) PKC-a (h) SgK071 IRE2 Bub1 CK2α1 Slob MEKK1 SLK - Superior data quality PCTAIRE2 CDKL3 GSK3β BubR1 MAP3K8 MAP2K5 MAP2K7 TNIK CK2α2 CDC7 RNAseL PIK3R4 MAP3K4 LOK PCTAIRE1 CDKL2 GSK3α MEKK2 MEK1 b SEK1 Akt2 (PKBb) (h) EphA1 (h) Lck (h) PKC- 1 (PRKCB1) (h) VRK3 MEKK3 MEK2 PAK6 PAK2 NRK CDKL1 CDKL5 CK1δ CLIK1 TBCK PINK1 VRK2 MKK3 PAK4 PAK1 - Custom assay development services CDKL4 SRPK1 CLK4 CK1ε PRP4 HIPK4 CLIK1L VRK1 MEKK6 MKK6 Akt3 (PKBg) (h) EphA2 (h) LTK (h) PKC-b2 (PRKCB2) (h) CLK1 HRI SgK269 PAK5 PAK3 CMGC MSSK1 ASK DYRK4 HIPK3 SgK223 CK1α2 SRPK2 CLK2 GCN2 TTBK2 CL1γ2 MAP3K7 OSRI STRAD DYRK3 DYRK1A HIPK2 TTBK1 CK1α1 AMPKa1b1g1(h) EphA3 (h) LynA (h) PKC-d (PRKCD) (h) CLK3 CK1γ1 PERK/PEK STLK3 DYRK2 DYRK1B HIPK1 CK1γ3 STLK6 PKR Bub1 PLK4 IKKε BubR1 CK1 AurA (Aur2/STK6) (h) EphA4 (h) LynB (h) PKC-h (PRKCH) (h) TBK1 IKKα SgK110 PLK1 ULK1 CAMKK1 IKKβ SgK069 ULK2 PLK2 CAMKK2 AurB (h) EphA5 (h) MAPK1 (ERK2, p42mapk) (h) PKC-g (PRKCG) (h) LabChip Technology SBK ULK4 SgK494 BARK1 PLK3 ULK3 Fused PDK1 BARK2 RHOK GRK5 AurA YANK1 MPSK1 GRK4 RSKL1 AurC (AURKC) (h) EphA6 (h) MAPK11 (p38b) (h) PKC-q (PRKCQ) (h) GAK Nek11 Nek2 Nek10 AurB YANK2 GRK7 GRK6 Our microfluidics technology separates RSKL2 AurC YANK3 AAK1 PKG2 PRKY Nek4 Nek8 Nek6 Axl (h) EphA7 (h) MAPK12 (p38g, SAPK3, ERK6) (h) PKC-z (PRKCZ) (h) BIKE PKG1 PRKX PKAγ PKAα Nek3 Nek9 Nek7 product and substrate electrophoretically MASTL PKAβ Nek5 LATS1 Trb2 Trb3 SgK495 MAST3 BLK (h) EphA8 (h) MAPK13 (p38d, SAPK4) (h) PKD2 (h) Nek1 CRIK LATS2 MSK1 p7056Kβ RSK3 Trb1 MAST2 and detects both strong and weak inhibitors PASK SGK1 MSK2 p7056K RSK4 RSK2 DMPK NDR1 Obscn~b Trio LKB1 MAST1 SGK3 RSK1 BMX (h) EphB2 (h) MAPK14 (p38a, SAPK2a) (h) PKG1a (h) NDR2 Obscn SPEG~b Trad Pim1 Pim2 DMPK2 PNK3 PNK2 Chk1 MAST4 SGK2 with high accuracy, and routinely identifies caMLCK SPEG Pim3 PNK1 ROCK1 SgK085 MRCKβ BRSK1 (h) EphB3 (h) MAPK3 (ERK1, p44mapk) (h) PKG1b (h) ROCK2 Akt3 PKCδ skMLCK smMLCK TTN MRCKα drug candidates that conventional techniques SSTK Akt2 PKCθ PKCε DAPK1 DAPK2 DRAK2 TSSK4 TSSK3 TSSK1 Akt1 PKCι PKCη BTK (h) EphB4 (h) MAPKAPK2 (h) PLK1 (h) DAPK3 DRAK1 TSSK2 PKCζ PKCγ miss. Direct benefits of this technology are PKD1 PKD2 STK33 HUNK MSK2~b MNK2 SNRK PKCα CaMK2a (h) ErbB4 (HER4) (h) MAPKAPK5 (PRAK) (h) RET (h) RSK2~b MSK1~b MNK1 PKD3 NIM1 MELK PKCβ1 minimized compound interferences, highest RSK3~b AGC RSK1~b RSK4~b CaMK2a (rat) FAK2 (PYK2/PTK2b) (h) MARK1 (h) ROCK1 (h) MAPKAPK5 SNARK AMPKα2 PhKγ2 ARK5 MAPKAPK3 Chk2 AMPKα1 PhKγ1 SIK data quality available on any screening MAPKAPK2 CAMK2d (h) FES (h) MEK1 (MAP2K1) (Human) ROCK2 (h) CASK QSK QIK BRSK2 MARK4 DCAMKL3 BRSK1 PSKH2 CaMKIIα MARK3 DCAMKL2 platform resulting in high Z’ values, few false PSKH1 δ CaMKIIγ CaMK4 (h) FGFR1 (h) MEK2 (MAP2K2) (Human) RSK1 (p90RSK/RPS6KA1) (h) CaMKII MARK2 DCAMKL1 VACAMKL CaMKIIβ CaMK4 MARK1 CaMKIβ CDK1 (h) FGFR3 (h) MELK (h) RSK2 (h) positives, few false negatives and analytical CaMKIγ CAMK CaMKIα CDK2/cyclinA (h) FGFR4 (h) Mer (h) RSK3 (h) quality reproducibility. CaMKIδ CDK6 (h) Flt1 (VEGFR1) (h) MET (h) SGK1 (h) The LabChip mobility-shift kinase assay CDK9/cyclin 1 (h) Flt3 (D835Y) (h) MKK6, (MAP2K6), (Human) skMLCK (MYLK2) (h) uses a microfluidic chip to measure the CHK1 (CHEK1) (h) Flt3 (h) MSK1 (RPS6KA5) (h) Sphingosine SK1 (h) conversion of a fluorescent peptide substrate CHK2 (CHEK2) (h) Flt4 (VEGFR3) (h) MST2 (STK3) (h) Sphingosine SK2 (h) to a phosphorylated product. The reaction CK1a (CSNK1A1) (h) FMS (CSF1R) (h) MST4 (h) Src (h) mixture, from a microtiter plate well, is CK1d (CSNK1D) (h) Fyn (h) NEK2 (h) Syk (h) introduced through a capillary sipper onto the CK2a1b (h) GSK-3a (h) p70S6K (h) Tie2 (h) chip, where the nonphosphorylated substrate c-Kit (h) GSK-3b (h) PAK1 (h) TrkA (NTRK1) (h) and phosphorylated product are separated cRAF (RAF1) (h) HGK (ZC1/MAP4K4) (h) PAK2 (h) TrkB (NTRK2) (h) by electrophoresis and detected via laser- CSK (h) IGF1R (h) PAK4 (h) TrkC (NTRK3) (h) induced fluorescence. The signature of the c-TAK (h) IKKa (h) PDGFa (D842V) (h) TTK (h) fluorescence signal over time reveals the DYRK1a (h) IKKb (h) PDGFRa (h) TYRO3 (h) DYRK1d (h) InsR (h) PDGFRb (h) YES (h) extent of the reaction. ZAP70 (h) KinaseScreen Programs KinaseScreen Programs

Protein Kinases KinaseScreen Mechanism of Action (MoA) Protein kinases are involved in a wide variety of disease states and over 30% of all spending for drug development focuses on • Understand how compounds interact with enzymatic targets this area of research. Through the use of the Caliper LabChip technology platform, Caliper Discovery Alliances & Services has developed KinaseScreen – a complete platform of kinase services to assist researchers in accelerating their lead identification • Quickly identify allosteric inhibitors and ATP competitors and optimization efforts in this very important area. • Characterize ATP competitors’ mode of inhibition (Competitive, Non-competitive, Un-competitive) • Determine K-off values Kinase Selectivity - KinaseAdvisor • Turnaround time: 5 to 6 weeks • Customizable panels of assays and test conditions - Large panel of optimized off the shelf assays - Check our website for updates - Select drug test concentrations and replicates - Option for ATP concentration at Km or other value - Inhibition or Activation assay formats - Screen against active or inactive enzyme forms

TRKC TRKB • Fast data turnaround times FGFR2 TRKA FGFR3 MuSK FGFR1 FLT1 TK DDR2 FGFR4 ROR2 KDR - Support new compound synthesis and DDR1 Ret ROR1 EphA5 EphB1 FLT4 EphA3 EphB2 IGF1R Src Axl lead optimization chemistry programs InsR Fms/CSFR HER2 Yes EphA4 EphB3 Mer Kit EGFR EphA6 EphB4 IRR Tyro3/Sky Fyn FLT3 HER4 EphA7 Ros Ron Frg HER3 EphA8 ALK Met PDGFRα • Fully Optimized Assay Protocols EphA2 β BLK PDGFR Ack LTK RYK EphA1 Tnk1 Lck FRK TIE1 EphB6 KinaseAdvisor CCK4/PTK7 TIE2 Tyk2 HCK Srm EphA10 - Caliper LabChip technology JAK1 Lyn Brk

Fes FAK Lmr1 JAK2 ANKRD3 CTK SuRTK106 Fer PYK2 Lmr2 JAK3 SgK228 List of Kinase Assays CSK JAK3~b - Physiologically relevant peptide substrates Syk RIPK2 ERK1 JAK2~b Lmr3 ZAP70 IRAK1 RIPK3 ERK2 Arg Etk/BMX LIMK1 TKL JNK1 Tyk2~b ANPα MOS IRAK3 LIMK2 Abl (E255K) (h) DYRK2 (h) InsR (h) - Activation Mode PDK1 (h) Abl BTK RIPK1 JNK3 ERK5 WNK1 JAK1~b ANPβ - Direct and simultaneous detection p38γ MLK4 SgK496 IRAK2 MLK2 TXK WNK3 LRRK1 TEST1 YSK1 p38δ JNK2 NLK HSER TEC PBK IRAK4 LRRK2 TEST2 ILK MLK3 MST3 Abl (G250E) (h) EGFR (ErbB1) (h) IRAK4 (h) PI3Ka (p110a/p85a) (h) WNK2 KHS1 of substrate and product p38β ERK3 SCYL1 CYDG MKL1 Wee1B ITK MLKL ALK1 TAK1 DLK KHS2 MST4 p38α ERK4 WNK4 CYGF CDK2 CHED Wee1 SCYL3 ALK2 HH498 LZK Abl (h) EGFR (L858R) (h) Jak2 (h) Pim1 (h) GCK MST1 CDK3 CRK7 ERK7 NRBP2 SCYL2 SgK307 ALK4 CDK10 MYT1 KSR ZAK HPK1 MST2 NRBP1 SgK424 TGFβR1 BMPR1A - Ratiometric method CDC2/CDK1 PITSLRE CDK9 CDK11 BMPR1B KSR2 ARAF BRAF Abl (Q252H) (h) EGFR (L861Q) (h) Jak3 (h) Pim2 (h) ALK7 CDK5 CDK7 CCRK CDK8 RAF1 MISR2 STE TGFβR2 NIK TAO1 PFTAIRE2 CDK4 MAK SgK196 BMPR2 MYO3A Abl (T315I) (h) EGFR (T790M) (h) JNK2 (h) PKA (h) - Homogeneous assay format KIS TAO2 ActR2 PFTAIRE1 CDK6 ICK SgK493 PRPK GCN2~b MYO3B TTK Tpl2/COT ActR2B TAO3 HGK IRE1 PCTAIRE3 MOK SgK396 Haspin MINK Akt1 (PKBa) (h) EGFR (T790M/L858R) (h) KDR (VEGFR2, FLK1) (h) PKC-a (h) SgK071 IRE2 Bub1 CK2α1 Slob MEKK1 SLK - Superior data quality PCTAIRE2 CDKL3 GSK3β BubR1 MAP3K8 MAP2K5 MAP2K7 TNIK CK2α2 CDC7 RNAseL PIK3R4 MAP3K4 LOK PCTAIRE1 CDKL2 GSK3α MEKK2 MEK1 b SEK1 Akt2 (PKBb) (h) EphA1 (h) Lck (h) PKC- 1 (PRKCB1) (h) VRK3 MEKK3 MEK2 PAK6 PAK2 NRK CDKL1 CDKL5 CK1δ CLIK1 TBCK PINK1 VRK2 MKK3 PAK4 PAK1 - Custom assay development services CDKL4 SRPK1 CLK4 CK1ε PRP4 HIPK4 CLIK1L VRK1 MEKK6 MKK6 Akt3 (PKBg) (h) EphA2 (h) LTK (h) PKC-b2 (PRKCB2) (h) CLK1 HRI SgK269 PAK5 PAK3 CMGC MSSK1 ASK DYRK4 HIPK3 SgK223 CK1α2 SRPK2 CLK2 GCN2 TTBK2 CL1γ2 MAP3K7 OSRI STRAD DYRK3 DYRK1A HIPK2 TTBK1 CK1α1 AMPKa1b1g1(h) EphA3 (h) LynA (h) PKC-d (PRKCD) (h) CLK3 CK1γ1 PERK/PEK STLK3 DYRK2 DYRK1B HIPK1 CK1γ3 STLK6 PKR Bub1 PLK4 IKKε BubR1 CK1 AurA (Aur2/STK6) (h) EphA4 (h) LynB (h) PKC-h (PRKCH) (h) TBK1 IKKα SgK110 PLK1 ULK1 CAMKK1 IKKβ SgK069 ULK2 PLK2 CAMKK2 AurB (h) EphA5 (h) MAPK1 (ERK2, p42mapk) (h) PKC-g (PRKCG) (h) LabChip Technology SBK ULK4 SgK494 BARK1 PLK3 ULK3 Fused PDK1 BARK2 RHOK GRK5 AurA YANK1 MPSK1 GRK4 RSKL1 AurC (AURKC) (h) EphA6 (h) MAPK11 (p38b) (h) PKC-q (PRKCQ) (h) GAK Nek11 Nek2 Nek10 AurB YANK2 GRK7 GRK6 Our microfluidics technology separates RSKL2 AurC YANK3 AAK1 PKG2 PRKY Nek4 Nek8 Nek6 Axl (h) EphA7 (h) MAPK12 (p38g, SAPK3, ERK6) (h) PKC-z (PRKCZ) (h) BIKE PKG1 PRKX PKAγ PKAα Nek3 Nek9 Nek7 product and substrate electrophoretically MASTL PKAβ Nek5 LATS1 Trb2 Trb3 SgK495 MAST3 BLK (h) EphA8 (h) MAPK13 (p38d, SAPK4) (h) PKD2 (h) Nek1 CRIK LATS2 MSK1 p7056Kβ RSK3 Trb1 MAST2 and detects both strong and weak inhibitors PASK SGK1 MSK2 p7056K RSK4 RSK2 DMPK NDR1 Obscn~b Trio LKB1 MAST1 SGK3 RSK1 BMX (h) EphB2 (h) MAPK14 (p38a, SAPK2a) (h) PKG1a (h) NDR2 Obscn SPEG~b Trad Pim1 Pim2 DMPK2 PNK3 PNK2 Chk1 MAST4 SGK2 with high accuracy, and routinely identifies caMLCK SPEG Pim3 PNK1 ROCK1 SgK085 MRCKβ BRSK1 (h) EphB3 (h) MAPK3 (ERK1, p44mapk) (h) PKG1b (h) ROCK2 Akt3 PKCδ skMLCK smMLCK TTN MRCKα drug candidates that conventional techniques SSTK Akt2 PKCθ PKCε DAPK1 DAPK2 DRAK2 TSSK4 TSSK3 TSSK1 Akt1 PKCι PKCη BTK (h) EphB4 (h) MAPKAPK2 (h) PLK1 (h) DAPK3 DRAK1 TSSK2 PKCζ PKCγ miss. Direct benefits of this technology are PKD1 PKD2 STK33 HUNK MSK2~b MNK2 SNRK PKCα CaMK2a (h) ErbB4 (HER4) (h) MAPKAPK5 (PRAK) (h) RET (h) RSK2~b MSK1~b MNK1 PKD3 NIM1 MELK PKCβ1 minimized compound interferences, highest RSK3~b AGC RSK1~b RSK4~b CaMK2a (rat) FAK2 (PYK2/PTK2b) (h) MARK1 (h) ROCK1 (h) MAPKAPK5 SNARK AMPKα2 PhKγ2 ARK5 MAPKAPK3 Chk2 AMPKα1 PhKγ1 SIK data quality available on any screening MAPKAPK2 CAMK2d (h) FES (h) MEK1 (MAP2K1) (Human) ROCK2 (h) CASK QSK QIK BRSK2 MARK4 DCAMKL3 BRSK1 PSKH2 CaMKIIα MARK3 DCAMKL2 platform resulting in high Z’ values, few false PSKH1 δ CaMKIIγ CaMK4 (h) FGFR1 (h) MEK2 (MAP2K2) (Human) RSK1 (p90RSK/RPS6KA1) (h) CaMKII MARK2 DCAMKL1 VACAMKL CaMKIIβ CaMK4 MARK1 CaMKIβ CDK1 (h) FGFR3 (h) MELK (h) RSK2 (h) positives, few false negatives and analytical CaMKIγ CAMK CaMKIα CDK2/cyclinA (h) FGFR4 (h) Mer (h) RSK3 (h) quality reproducibility. CaMKIδ CDK6 (h) Flt1 (VEGFR1) (h) MET (h) SGK1 (h) The LabChip mobility-shift kinase assay CDK9/cyclin 1 (h) Flt3 (D835Y) (h) MKK6, (MAP2K6), (Human) skMLCK (MYLK2) (h) uses a microfluidic chip to measure the CHK1 (CHEK1) (h) Flt3 (h) MSK1 (RPS6KA5) (h) Sphingosine SK1 (h) conversion of a fluorescent peptide substrate CHK2 (CHEK2) (h) Flt4 (VEGFR3) (h) MST2 (STK3) (h) Sphingosine SK2 (h) to a phosphorylated product. The reaction CK1a (CSNK1A1) (h) FMS (CSF1R) (h) MST4 (h) Src (h) mixture, from a microtiter plate well, is CK1d (CSNK1D) (h) Fyn (h) NEK2 (h) Syk (h) introduced through a capillary sipper onto the CK2a1b (h) GSK-3a (h) p70S6K (h) Tie2 (h) chip, where the nonphosphorylated substrate c-Kit (h) GSK-3b (h) PAK1 (h) TrkA (NTRK1) (h) and phosphorylated product are separated cRAF (RAF1) (h) HGK (ZC1/MAP4K4) (h) PAK2 (h) TrkB (NTRK2) (h) by electrophoresis and detected via laser- CSK (h) IGF1R (h) PAK4 (h) TrkC (NTRK3) (h) induced fluorescence. The signature of the c-TAK (h) IKKa (h) PDGFa (D842V) (h) TTK (h) fluorescence signal over time reveals the DYRK1a (h) IKKb (h) PDGFRa (h) TYRO3 (h) DYRK1d (h) InsR (h) PDGFRb (h) YES (h) extent of the reaction. ZAP70 (h) KinaseScreen - RapidKinase • Set panels of kinases assays - RapidKinase 48 with broad representation of the kinome Discovery Alliances & Services - RapidKinase 200 for wide kinase selectivity screens • Create your panel using any combination of plates • Relies on Caliper ProfilerPro plates reagents: - 24 kinase assays per ProfilerPro plate - Highly reproducible data - Assays run at apparent ATP Km

KinaseScreen CDAS| Programs

Kinases are an important class of enyzmes involved in signal transduction and signaling networks within cells. Kinase signal- ing pathways play a fundamental role in regulating cell prolif- eration, cell metabolism and cell death. Research shows that changes in protein kinase activity within a cell can lead to several disease states, most notably cancer. With this knowledge base, scientists have been investigating the ability of drugs to block various protein kinases as a cancer therapy. This approach has proved successful with the discovery of several kinase inhibitor drugs for the treatment of various cancers. These drugs include Gleevec®, Iressa® and Tarceva®. In addition to their involvement in cancer, protein kinases are implicated in diabetes, inflamma- tion and neurological development and degeneration.

Discovery Alliances & Services ©2010 Caliper Life Sciences, Inc. All rights reserved. Preclinical Contract Services Caliper, the Caliper logo, KinaseScreen, KinaseAdvisor, ProfilerPro, CDAS and Discovery 7170 Standard Drive Alliances & Services are tradenames and/or trademarks of Caliper Life Sciences, Inc. Hanover, Maryland 21076-1334 USA All other names are trademarks of their respective companies. Tel: 1.410.712.4410 / 1.800.543.4141 CDAS-BR-01 Nov 10