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scanEDGE^℠ Kinase Assay Panel

An economical approach to surveying the human kinome, scanEDGE includes 97 kinases distributed throughout the AGC, CAMK, CMGC, CK1, STE, TK, TKL, lipid, and atypical kinase families, plus important mutant forms. scanEDGE is an economical alternative to scanMAX and useful to assess compound selectivity at all stages of drug discovery and development, from lead discovery & hit identification to lead optimization.

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Panel Features & Benefits

Panel of 97 kinases distributed across the kinome
High-quality reproducible data
Rapid turnaround time
Broad dynamic range: detect compounds with Kds <100 pm to >10 uM
Flexible - standard and custom panels
Detection of multiple inhibitor types (e.g. type I, II & non-ATP competitive)
Economically priced

How it Works

Assay Sensitivity, Quality, Reproducibility & Type II Interactions

Assay Sensitivity

Binding constant (Kd) determinations for the indicated compounds against LOK demonstrate the broad range (> 5 logs) of interaction affinities quantitatively measured using the KINOMEscan assay platform. Assays are performed at low kinase concentrations (<0.1 nM), which enables the measurement of accurate Kd values in the pM range [click graph to enlarge].

Assay Quality

Average Z' values and standard deviations were calculated for each kinase based on fourteen control wells per experiment in over 135 independent experiments spanning a period of sixteen months. Average Z' for all assay is 0.71 [click graph to enlarge].

Data Consistency

Profiling of the indicated compounds at 10uM in fourteen independent experiments against 442 kinases over a one year period. Correlation analysis was performed in a pair-wise comparison to calculate the correlation coefficient. The correlation coefficients range from 0.91 to 0.97 with an average of 0.95 [click graph to enlarge].

Detection of Type II Kinase Inhibitors

Activation State Specific Kinase Inhibitor Imatinib and phosphorylated ABL1

Binding constant (Kd) determinations were measured for interactions between imatinib, a known Type II inhibitor, and ABL preparations differentially phosphorylated on the A-loop. Imatinib exhibited a 30-fold affinity preference for the non-phosphorylated state (Kd = 1.4 nM) relative to the phosphorylated state (Kd = 56 nM) [click graph to enlarge].

scanEDGE Assay Panel

Listed below are the assays currently available for screening and profiling.

KGS ▲	Kinase Name	Entrez Gene Symbol
ABL1(E255K)-phosphorylated	c-abl oncogene 1, receptor tyrosine kinase	ABL1
ABL1(T315I)-phosphorylated	c-abl oncogene 1, receptor tyrosine kinase	ABL1
ABL1-nonphosphorylated	c-abl oncogene 1, receptor tyrosine kinase	ABL1
ABL1-phosphorylated	c-abl oncogene 1, receptor tyrosine kinase	ABL1
ACVR1B	activin A receptor, type IB	ACVR1B
ADCK3	coenzyme Q8A	CABC1
AKT1	v-akt murine thymoma viral oncogene homolog 1	AKT1
AKT2	v-akt murine thymoma viral oncogene homolog 2	AKT2
ALK	anaplastic lymphoma receptor tyrosine kinase	ALK
AURKA	aurora kinase A	AURKA
AURKB	aurora kinase B	AURKB
AXL	AXL receptor tyrosine kinase	AXL
BMPR2	bone morphogenetic protein receptor, type II (serine/threonine kinase)	BMPR2
BRAF	v-raf murine sarcoma viral oncogene homolog B1	BRAF
BRAF(V600E)	v-raf murine sarcoma viral oncogene homolog B1	BRAF
BTK	Bruton agammaglobulinemia tyrosine kinase	BTK
CDK11	cyclin-dependent kinase 19	CDK19
CDK2	cyclin-dependent kinase 2	CDK2
CDK3	cyclin-dependent kinase 3	CDK3
CDK7	cyclin-dependent kinase 7	CDK7
CDK9	cyclin-dependent kinase 9	CDK9
CHEK1	checkpoint kinase 1	CHEK1
CSF1R	colony stimulating factor 1 receptor	CSF1R
CSNK1D	casein kinase 1, delta	CSNK1D
CSNK1G2	casein kinase 1, gamma 2	CSNK1G2
DCAMKL1	doublecortin-like kinase 1	DCLK1
DYRK1B	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B	DYRK1B
EGFR	epidermal growth factor receptor	EGFR
EGFR(L858R)	epidermal growth factor receptor	EGFR
EPHA2	EPH receptor A2	EPHA2
ERBB2	erb-b2 receptor tyrosine kinase 2	ERBB2
ERBB4	erb-b2 receptor tyrosine kinase 4	ERBB4
ERK1	mitogen-activated protein kinase 3	MAPK3
FAK	PTK2 protein tyrosine kinase 2	PTK2
FGFR2	fibroblast growth factor receptor 2	FGFR2
FGFR3	fibroblast growth factor receptor 3	FGFR3
FLT3	fms-related tyrosine kinase 3	FLT3
GSK3B	glycogen synthase kinase 3 beta	GSK3B
IGF1R	insulin-like growth factor 1 receptor	IGF1R
IKK-alpha	conserved helix-loop-helix ubiquitous kinase	CHUK
IKK-beta	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	IKBKB
INSR	insulin receptor	INSR
JAK2(JH1domain-catalytic)	Janus kinase 2	JAK2
JAK3(JH1domain-catalytic)	Janus kinase 3	JAK3
JNK1	mitogen-activated protein kinase 8	MAPK8
JNK2	mitogen-activated protein kinase 9	MAPK9
JNK3	mitogen-activated protein kinase 10	MAPK10
KIT	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	KIT
KIT(D816V)	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	KIT
KIT(V559D,T670I)	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	KIT
LKB1	serine/threonine kinase 11	STK11
MAP3K4	mitogen-activated protein kinase kinase kinase 4	MAP3K4
MAPKAPK2	mitogen-activated protein kinase-activated protein kinase 2	MAPKAPK2
MARK3	MAP/microtubule affinity-regulating kinase 3	MARK3
MEK1	mitogen-activated protein kinase kinase 1	MAP2K1
MEK2	mitogen-activated protein kinase kinase 2	MAP2K2
MET	met proto-oncogene (hepatocyte growth factor receptor)	MET
MKNK1	MAP kinase interacting serine/threonine kinase 1	MKNK1
MKNK2	MAP kinase interacting serine/threonine kinase 2	MKNK2
MLK1	mitogen-activated protein kinase kinase kinase 9	MAP3K9
p38-alpha	mitogen-activated protein kinase 14	MAPK14
p38-beta	mitogen-activated protein kinase 11	MAPK11
PAK1	p21 protein (Cdc42/Rac)-activated kinase 1	PAK1
PAK2	p21 protein (Cdc42/Rac)-activated kinase 2	PAK2
PAK4	p21 protein (Cdc42/Rac)-activated kinase 4	PAK4
PCTK1	cyclin-dependent kinase 16	CDK16
PDGFRA	platelet-derived growth factor receptor, alpha polypeptide	PDGFRA
PDGFRB	platelet-derived growth factor receptor, beta polypeptide	PDGFRB
PDPK1	3-phosphoinositide dependent protein kinase-1	PDPK1
PIK3C2B	phosphoinositide-3-kinase, class 2, beta polypeptide	PIK3C2B
PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	PIK3CA
PIK3CG	phosphoinositide-3-kinase, catalytic, gamma polypeptide	PIK3CG
PIM1	pim-1 oncogene	PIM1
PIM2	pim-2 oncogene	PIM2
PIM3	pim-3 oncogene	PIM3
PKAC-alpha	protein kinase, cAMP-dependent, catalytic, alpha	PRKACA
PLK1	polo-like kinase 1	PLK1
PLK3	polo-like kinase 3	PLK3
PLK4	polo-like kinase 4	PLK4
PRKCE	protein kinase C, epsilon	PRKCE
RAF1	v-raf-1 murine leukemia viral oncogene homolog 1	RAF1
RET	ret proto-oncogene	RET
RIOK2	RIO kinase 2	RIOK2
ROCK2	Rho-associated, coiled-coil containing protein kinase 2	ROCK2
RSK2(Kin.Dom.1-N-terminal)	ribosomal protein S6 kinase, 90kDa, polypeptide 3	RPS6KA3
SNARK	NUAK family, SNF1-like kinase, 2	NUAK2
SRC	SRC proto-oncogene, non-receptor tyrosine kinase	SRC
SRPK3	SFRS protein kinase 3	SRPK3
TGFBR1	transforming growth factor, beta receptor 1	TGFBR1
TIE2	TEK tyrosine kinase, endothelial	TEK
TRKA	neurotrophic tyrosine kinase, receptor, type 1	NTRK1
TSSK1B	testis-specific serine kinase 1B	TSSK1B
TYK2(JH1domain-catalytic)	tyrosine kinase 2	TYK2
ULK2	unc-51-like kinase 2	ULK2
VEGFR2	kinase insert domain receptor (a type III receptor tyrosine kinase)	KDR
YANK3	serine/threonine kinase 32C	STK32C
ZAP70	zeta-chain (TCR) associated protein kinase 70kDa	ZAP70

Data Analysis & Interpretation

Definitions

Percent of Control (%Ctrl)

The results for single concentration (primary screen) binding interactions for tested compound(s) are reported in your study report and spreadsheets as '%Ctrl' and is calculated in the following manner:

    test compound = client supplied compound
    negative control = DMSO (100% control)
    positive control = control compound (0% control)

Binding Constant (Kd)

The results for an 11-point dose response curve compound/kinase interactions are reported in your study report and spreadsheets as Kd, which are values derived using the Hill equation:
Hill equation used for calculating binding constants

The Hill Slope is set to -1. Curves are fitted using a non-linear least square fit with the Levenberg-Marquardt algorithm.

Selectivity Score (S-Scores)

Selectivity Score or S-score is a quantitative measure of compound selectivity. It is calculated by dividing the number of kinases that compounds bind to by the total number of distinct kinases tested, excluding mutant variants.
selectivity score calculation

This value can be calculated using %Ctrl as a potency threshold (below) and provides a quantitative method of describing compound selectivity to facilitate comparison of different compounds.

S(35) = (number of non-mutant kinases with %Ctrl <35)/(number of non-mutant kinases tested)

S(10) = (number of non-mutant kinases with %Ctrl <10)/(number of non-mutant kinases tested)

S(1) = (number of non-mutant kinases with %Ctrl <1)/(number of non-mutant kinases tested)

Using S-Score Data to Quantitate Selectivity

Selectivity Profile for 38 Small Molecule Kinase Inhibitors

32 small molecule compound calibration curve

KINOMEscan's in vitro competition binding assay was used to evaluate 38 kinase inhibitors against a panel of 287 distinct human protein kinases (~55% of the predicted human protein kinome), and three lipid kinases. The compounds tested included 21 tyrosine kinase inhibitors, 15 serine-threonine kinase inhibitors, 1 lipid kinase inhibitor, and staurosporine. S(35), 10uM = (number of non-mutant kinases with %Ctrl <35)/(290 kinases tested; 27 mutant variants were excluded from this analysis). Compounds approved for use in humans (as of August, 2007) are highlighted (gray bars) [click graph to enlarge].

TREEspot Kinase Dendrograms: A Visual Representation of Compound Selectivity

TREEspot is an innovative compound profile visualization tool for visualizing screening data. Kinases found to bind are marked with red circles, where larger circles indicate higher-affinity binding.

RSK Inhibitor

RSK Inhibitor small panel versus large panel selectivity

RSK inhibitor was reported in published findings to be a selective RSK kinase inhibitor on the basis of kinase profiling against a panel of 54 kinases. Selectivity profiling against the scanMAX kinase assay panel (then 402) revealed additional interactions not previously identified [click graph to enlarge].

TREEspot Compound Profile Visualization Tool

TREEspot is an innovative, secure access, web-based, compound profile visualization tool for analysis of KINOMEscan screening data. TREEspot is an ideal companion tool for existing data analysis applications and facilitates compound profile visualization through its simple yet powerful user interface.

Gain new perspectives of kinase profile data in a visual environment and distill essential knowledge to drive your discovery programs. TREEspot is provided as a complimentary tool to our clients. To learn more about how you can visualize your data using TREEspot or to request access credentials, please contact KINOMEscan.

Easy-to-use
Facilitates evaluation and analysis of profiling data
Generates publication quality of TREEspot images
Provides global visualization of profile data
Visualize your data in a whole new way

scanMAX Kinase Dendrogram

scanEDGE℠ Kinase Assay Panel