|
Inhibition of human recombinant TIE2 by HTRF assay
|
Homo sapiens
|
18.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole oximes as potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases.
Year : 2008
Volume : 18
Issue : 6
First Page : 1916
Last Page : 1921
Authors : Dandu R, Zulli AL, Bacon ER, Underiner T, Robinson C, Chang H, Miknyoczki S, Grobelny J, Ruggeri BA, Yang S, Albom MS, Angeles TS, Aimone LD, Hudkins RL.
Abstract : Fused dihydroindazolopyrrolocarbazole oximes have been identified as low nanomolar, potent dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors with excellent cellular potency. Development of the structure-activity relationships (SAR) led to identification of compounds 35 and 40 as potent, selective dual TIE-2/VEGF-R2 inhibitors with favorable pharmacokinetic properties. Compound 35 was orally active in tumor models with no observed toxicity.
|
Inhibition of human recombinant VEGFR2 by HTRF assay
|
Homo sapiens
|
11.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole oximes as potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases.
Year : 2008
Volume : 18
Issue : 6
First Page : 1916
Last Page : 1921
Authors : Dandu R, Zulli AL, Bacon ER, Underiner T, Robinson C, Chang H, Miknyoczki S, Grobelny J, Ruggeri BA, Yang S, Albom MS, Angeles TS, Aimone LD, Hudkins RL.
Abstract : Fused dihydroindazolopyrrolocarbazole oximes have been identified as low nanomolar, potent dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors with excellent cellular potency. Development of the structure-activity relationships (SAR) led to identification of compounds 35 and 40 as potent, selective dual TIE-2/VEGF-R2 inhibitors with favorable pharmacokinetic properties. Compound 35 was orally active in tumor models with no observed toxicity.
|
Inhibition of human recombinant Tie2
|
Homo sapiens
|
620.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of imidazole vinyl pyrimidines as a novel class of kinase inhibitors which inhibit Tie-2 and are orally bioavailable.
Year : 2008
Volume : 18
Issue : 16
First Page : 4723
Last Page : 4726
Authors : Buttar D, Edge M, Emery SC, Fitzek M, Forder C, Griffen A, Hayter B, Hayward CF, Hopcroft PJ, Luke RW, Page K, Stawpert J, Wright A.
Abstract : Tie-2 is a receptor tyrosine kinase which is involved in angiogenesis and thereby growth of human tumours. The discovery and SAR of a novel class of imidazole-vinyl-pyrimidine kinase inhibitors, which inhibit Tie-2 in vitro is reported. Their synthesis was carried out by condensation of imidazole aldehydes with methyl pyrimidines. These compounds are lead-like, with low molecular weight, good physical properties and oral bioavailability.
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP4K4
|
None
|
158.49
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: AXL
|
None
|
630.96
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LTK
|
None
|
199.53
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAPK14
|
None
|
316.23
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FRK
|
None
|
25.12
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ALK
|
None
|
794.33
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PLK4
|
None
|
251.19
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: RET
|
None
|
31.62
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LCK
|
None
|
100.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ACVR1
|
None
|
398.11
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK6
|
None
|
630.96
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FGFR1
|
None
|
15.85
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LYN
|
None
|
100.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ITK
|
None
|
398.11
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TAO1
|
None
|
316.23
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: BLK
|
None
|
316.23
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SRC
|
None
|
125.89
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PDGFRB
|
None
|
398.11
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ABL1
|
None
|
79.43
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: KDR
|
None
|
2.512
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: EPHA2
|
None
|
501.19
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MINK
|
None
|
251.19
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PTK6
|
None
|
316.23
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PDGFRA
|
None
|
398.11
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK12
|
None
|
251.19
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP4K5
|
None
|
251.19
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT4
|
None
|
100.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FYN
|
None
|
501.19
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT1
|
None
|
25.12
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SLK
|
None
|
10.0
nM
|
|
Title : PubChem BioAssay data set
|
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FGFR3
|
None
|
7.943
nM
|
|
Title : PubChem BioAssay data set
|
Inhibition of VEGFR2 by cell based assay
|
None
|
6.0
nM
|
|
Journal : J. Med. Chem.
Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
Year : 2012
Volume : 55
Issue : 24
First Page : 10797
Last Page : 10822
Authors : Musumeci F, Radi M, Brullo C, Schenone S.
Abstract : The recent launch onto the market of five VEGFR inhibitors indicates the therapeutic value of these agents and the importance of the research in the field of angiogenesis inhibitors for future oncologic therapy. In this Perspective we briefly report the inhibitors that are in clinical use, while we dedicate two wider sections to the compounds that are in clinical trials and to the new derivatives appearing in the literature. We especially consider the medicinal chemistry aspect of the topic and report the structure-activity relationship studies and the binding mode of some inhibitors as well as the biological data of the compounds discovered in the past 5 years.
|
Inhibition of FGFRbeta
|
None
|
9.0
nM
|
|
Journal : J. Med. Chem.
Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
Year : 2012
Volume : 55
Issue : 24
First Page : 10797
Last Page : 10822
Authors : Musumeci F, Radi M, Brullo C, Schenone S.
Abstract : The recent launch onto the market of five VEGFR inhibitors indicates the therapeutic value of these agents and the importance of the research in the field of angiogenesis inhibitors for future oncologic therapy. In this Perspective we briefly report the inhibitors that are in clinical use, while we dedicate two wider sections to the compounds that are in clinical trials and to the new derivatives appearing in the literature. We especially consider the medicinal chemistry aspect of the topic and report the structure-activity relationship studies and the binding mode of some inhibitors as well as the biological data of the compounds discovered in the past 5 years.
|
Inhibition of VEGFR2
|
None
|
11.0
nM
|
|
Journal : J. Med. Chem.
Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
Year : 2012
Volume : 55
Issue : 24
First Page : 10797
Last Page : 10822
Authors : Musumeci F, Radi M, Brullo C, Schenone S.
Abstract : The recent launch onto the market of five VEGFR inhibitors indicates the therapeutic value of these agents and the importance of the research in the field of angiogenesis inhibitors for future oncologic therapy. In this Perspective we briefly report the inhibitors that are in clinical use, while we dedicate two wider sections to the compounds that are in clinical trials and to the new derivatives appearing in the literature. We especially consider the medicinal chemistry aspect of the topic and report the structure-activity relationship studies and the binding mode of some inhibitors as well as the biological data of the compounds discovered in the past 5 years.
|
Binding affinity to human acrylodan-labeled N-terminal His-tagged DDR2 (558 to 855 aa) by FLiK assay
|
Homo sapiens
|
422.0
nM
|
|
Journal : J. Med. Chem.
Title : Identification of type II and III DDR2 inhibitors.
Year : 2014
Volume : 57
Issue : 10
First Page : 4252
Last Page : 4262
Authors : Richters A, Nguyen HD, Phan T, Simard JR, Grütter C, Engel J, Rauh D.
Abstract : Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.
|
Inhibition of wild type DDR2 (unknown origin) preincubated for 30 mins before substrate addition by FRET assay
|
Homo sapiens
|
24.0
nM
|
|
Journal : J. Med. Chem.
Title : Identification of type II and III DDR2 inhibitors.
Year : 2014
Volume : 57
Issue : 10
First Page : 4252
Last Page : 4262
Authors : Richters A, Nguyen HD, Phan T, Simard JR, Grütter C, Engel J, Rauh D.
Abstract : Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.
|
Inhibition of DDR2 T654M mutant (unknown origin) preincubated for 30 mins before substrate addition by FRET assay
|
Homo sapiens
|
450.0
nM
|
|
Journal : J. Med. Chem.
Title : Identification of type II and III DDR2 inhibitors.
Year : 2014
Volume : 57
Issue : 10
First Page : 4252
Last Page : 4262
Authors : Richters A, Nguyen HD, Phan T, Simard JR, Grütter C, Engel J, Rauh D.
Abstract : Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.
|
Inhibition Assay: Inhibition of recombinant VEGFR-2 tyrosine kinase using exogenous substrate.
|
Homo sapiens
|
10.55
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
Inhibition Assay: Inhibition of recombinant FGFR-2 tyrosine kinase using exogenous substrate.
|
Homo sapiens
|
8.79
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
Inhibition Assay: Inhibition of VEGF-stimulated VEGFR-2 autophosphorylation in intact cells.
|
Homo sapiens
|
5.27
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
207.0
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
8.5
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
3.08
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
33.9
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
None
|
500.0
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
122.0
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
419.0
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
54.2
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
None
|
161.0
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
1.27
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
10.1
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
In Vitro Inhibition Assay: In Vitro Inhibition of Tyrosine Kinases using a 10-point Titration Curve.
|
Homo sapiens
|
11.1
nM
|
|
Title : Ocular formulations for drug-delivery to the posterior segment of the eye
Year : 2016
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
4.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
281.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
67.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
669.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
226.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
396.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
894.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
627.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
135.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
772.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
775.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
341.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
958.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
904.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
268.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
515.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
5.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
|
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
|
Homo sapiens
|
881.0
nM
|
|
Journal : Science
Title : The target landscape of clinical kinase drugs.
Year : 2017
Volume : 358
Issue : 6367
Authors : Klaeger S, Heinzlmeir S and Wilhelm M et al
Abstract : Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
