Accelerate Your Drug Discovery Process! Kinase Prof iling Services 192 Validated Targets* Kinase Profiling / IC50 Services Massive Kinome Coverage at two ATP concentrations We have expanded our Profiling / IC50 Services to facilitate inhibitor-type determinations by adding optional profiling at 1mM ATP, approaching physiological ATP levels. This important adjunct to our existing services, performed at [ATP]=Km bin., extends to 192 human kinases* (123 TKs including mutants, 69 STKs) and allows the impact of ATP concentration on kinase-inhibitory activity to be rapidly visualized and assessed. A list of kinases available for IC50 determinations using 1mM ATP is shown on the reverse side. Despite the sensitivity offered by performing in vitro assays at ATP concentrations approximating Km, physiological conditions are seldom the same. Inhibitory potency and selectivity may vary with the concentration of ATP available; results contrasting ATP Km bin. vs. 1mM ATP are shown below. * As of May 22 2017 Example of Analysis Differential Kinase Selectivity : ATP Km bin. vs. 1mM ATP Sunitinib vs. TKs at [ATP]=Km bin. Sunitinib vs. TKs at [ATP]=1mM PDGFRB PDGFRA PDGFRB PDGFRA HER2 FMS HER2 FMS TYRO3 EGFR TYRO3 EGFR KIT KIT MER HER4 MER AXL HER4 TK FLT3 AXL TK FLT3 RON HER3/ErbB3 KDR RON HER3/ErbB3 KDR RYK FLT1 MET RYK TYK2 FLT1 MET TYK2 FLT4 TIE1 JAK3 FLT4 TIE1 JAK3 JAK1 FGFR4 JAK1 FGFR4 JAK2 FGFR1 TIE2 JAK2 FGFR3 FGFR1 TIE2 TNK1 FGFR3 TNK1 IGF1R ACK IGF1R IRR ACK LMR1 IRR FGFR2 RET LMR1 LMR2 FGFR2 RET LMR2 INSR INSR FER FES FER FES LMR3 LTK LMR3 LTK ALK ROS ALK ROS BTK BTK EphA10 BMX ITK EphA10 SuRTK106 BMX ITK SuRTK106 CCK4 TXK CSK CCK4 TXK CSK EphB6 PYK2 EphB6 PYK2 TEC CTK ZAP70 TEC CTK ZAP70 FAK EphA1 FAK SRM EphA1 SYK SRM SYK ABL ABL BRK ROR2 BRK ROR2 ROR1 ARG ROR1 ARG MUSK FRK EphA2 MUSK FRK EphA2 BLK DDR1 DDR2 TRKA BLK DDR1 DDR2 TRKA LCK EphA8 IC50 (nM) LCK EphA8 HCK TRKC HCK TRKC LYN FGR TRKB LYN FGR TRKB EphB4 EphB4 SRC FYN EphA6 SRC FYN EphA6 YES EphB3 EphB1 YES EphB3 EphB1 EphA7 EphA7 EphB2 HIPK2 EphB2 EphA4 EphA4 EphA3 0.1 1 10 100 1,000>10,000 EphA3 EphA5 EphA5 Applicable for screening inhibitors that are non-competitive for the ATP binding site, the apparent selectivity of the inhibitor when measured at [ATP] Km bin. was further enhanced at 1mM ATP, in this experiment. Higher ATP concentrations, approaching physiological, provide conditions similar to cellular proliferation assays for ligands targeted to activated kinases. Having both ATP Km bin. and 1mM ATP assays provides insight to in vivo pharmacological behavior. Ready to start? Download our convenient Application Form at www.carnabio.com, complete the necessary fields and E-mail your sales representative or [email protected]. Our Application Form for Activity Based Profiling based on our Kinase Panel at [ATP]=Km bin. can also be downloaded from our website. If you are a new customer, we recommend executing a CDA to assure complete confidentiality. Km bin. 1mM Carna's wholly-owned subsidiary Carna Biosciences, Inc. CarnaBio USA, Inc. BMA 3F, 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047 JAPAN 209 West Central Street, Suite 307, Natick, MA 01760 USA TEL： 078-302-7091 / FAX： 078-302-7086 TEL: +1-508-650-1244 / Toll-Free: +1-888-645-1233 E-mail： [email protected] E-mail: [email protected] / FAX: +1-508-650-1722 www.carnabio.com ©2009 Carna Biosciences, Inc. QuickScout™ Custom Profiling from Carna Biosciences, Inc. 192 human kinases (123 TKs, 69 STKs) for 1mM ATP We test your drug candidates against any or all of the 192 Kinases shown below using ATP at a concentration of 1mM. Our service is the industry's most complete specificity and selectivity assessment, based on IC50 values. Additional information on each kinase and assay conditions can be obtained by visiting www.carnabio.com and downloading our Kinase Profiling Book. Tyrosine Kinases Tyrosine Kinases Serine/Threonine Kinases ABL(ABL1) FYN [isoform a] AKT1 ABL(ABL1) [E255K] FYN [isoform b] AMPKα1/β1/γ1(PRKAA1/B1/G1) ABL(ABL1) [T315I] HCK AurA(AURKA) ACK(TNK2) HER2(ERBB2) AurB(AURKB)/INCENP ALK HER4(ERBB4) AurC(AURKC) ALK [C1156Y] IGF1R BRSK1 ALK [F1174L] INSR CaMK4 ALK [G1202R] IRR(INSRR) CDC2/CycB1 ALK [G1269A] ITK CDC7/ASK ALK [L1196M] JAK1 CDK2/CycA2 ALK [R1275Q] JAK2 CDK2/CycE1 ALK [T1151_L1152insT] JAK3 CDK4/CycD3 ARG(ABL2) KDR CDK5/p25 AXL KIT CDK6/CycD3 BLK KIT [D816E] CDK7/CycH/MAT1 BMX KIT [D816V] CDK9/CycT1 BRK(PTK6) KIT [D816Y] CHK1(CHEK1) BTK KIT [T670I] CHK2(CHEK2) BTK[C481S] KIT [V560G] CK1α(CSNK1A1) CSK KIT [V654A] CK1ε(CSNK1E) DDR1 LCK CK2α1/β(CSNK2A1/B) DDR2 LTK CLK1 EGFR LYNa CLK2 EGFR [d746-750] LYNb DAPK1 EGFR [d746-750/T790M] MER(MERTK) DYRK1A EGFR [L858R] MET DYRK1B EGFR [L861Q] MET [D1228H] Erk1(MAPK3) EGFR [T790M] MET [M1250T] Erk2(MAPK1) EGFR [T790M/L858R] MET [Y1235D] GSK3α(GSK3A) EML4-ALK MUSK GSK3β(GSK3B) EPHA1 NPM1-ALK HIPK4 EPHA2 PDGFRα(PDGFRA) HGK(MAP4K4) EPHA3 PDGFRα(PDGFRA) [D842V] IKKβ(IKBKB) EPHA4 PDGFRα(PDGFRA) [T674I] JNK1(MAPK8) EPHA5 PDGFRα(PDGFRA) [V561D] JNK2(MAPK9) EPHA6 PDGFRβ(PDGFRB) JNK3(MAPK10) EPHA7 PYK2(PTK2B) MAPKAPK2 EPHA8 RET MINK(MINK1) EPHB1 RET [G691S] MST1(STK4) EPHB2 RET [M918T] NEK1 EPHB3 RET [S891A] NEK2 EPHB4 RET [Y791F] NEK6 FAK(PTK2) RON(MST1R) NEK7 FER ROS(ROS1) NEK9 FES SRC p38α(MAPK14) FGFR1 SRM(SRMS) p38β(MAPK11) FGFR1 [V561M] SYK p38γ(MAPK12) FGFR2 TEC p38δ(MAPK13) FGFR2 [V564I] TIE2(TEK) p70S6K(RPS6KB1) FGFR3 TNK1 PAK2 FGFR3 [K650E] TRKA(NTRK1) PBK FGFR3 [K650M] TRKB(NTRK2) PDK1(PDPK1) FGFR3 [V555L] TRKC(NTRK3) PIM1 FGFR3 [V555M] TXK PIM2 FGFR4 TYK2 PKACα(PRKACA) FGFR4 [N535K] TYRO3 PKCα(PRKCA) FGFR4 [V550E] YES(YES1) PKCε(PRKCE) FGFR4 [V550L] YES(YES1) [T348I] PKD2(PRKD2) FGR ZAP70 PLK1 FLT1 PLK3 FLT3 Tyrosine Kinases 123 QIK(SNF1LK2) FLT4 Serine/Threonine Kinases 69 ROCK1 FMS(CSF1R) Total 192 targets RSK1(RPS6KA1) FRK RSK3(RPS6KA2) Updated: 2017/5/22 RSK4(RPS6KA6) SGK SIK(SNF1LK) TNIK TSSK1.