spebrutinib [Ligand Id: 7837] activity data from GtoPdb and ChEMBL
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| ChEMBL ligand: CHEMBL3301625 (Btk inhibitor cc-292, Espebrutinib, Spebrutinib) |
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| DB | Assay description | Assay Type | Standard value | Standard parameter | Original value | Original units | Original parameter | Reference |
|---|---|---|---|---|---|---|---|---|
| BMX non-receptor tyrosine kinase/Cytoplasmic tyrosine-protein kinase BMX in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3834] [GtoPdb: 1942] [UniProtKB: P51813] | ||||||||
| ChEMBL | Inhibition of full length recombinant human N-terminal GST-tagged BMX expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr)4:1 as substrate pretreated for 60 mins followed by substrate addition after 1 hr by ADP-Glo luminescence assay | B | 5.57 | pIC50 | 2665 | nM | IC50 | Eur J Med Chem (2017) 131: 107-125 [PMID:28315597] |
| ChEMBL | Lanthscreen Eu Kinase Binding Assay : Lanthscreen Eu Kinase Binding assay for BMX is performed as described above for BTK except that 1 nM human recombinant full length TEC (His-tagged) kinase and 1 nM Alexa Fluor647-labeled Kinase Tracer #178 were used instead.Representative compounds of the present invention are assessed for inhibition of BTK, BMX, and TXK measuring phosphorylation of a substrate (Z′-LYTE assay, Life Technologies) and TEC measuring displacement of a tracer (Lanthscreen® Eu Kinase Binding assay, Life Technologies). | B | 8.49 | pIC50 | 3.2 | nM | IC50 | US-9975882-B2. Heteroaromatic compounds as BTK inhibitors (2018) |
| Early activation antigen CD69 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3308911] [UniProtKB: Q07108] | ||||||||
| ChEMBL | Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry | B | 5.51 | pIC50 | 3100 | nM | IC50 | J Med Chem (2022) 65: 1206-1224 [PMID:34734694] |
| epidermal growth factor receptor/Epidermal growth factor receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL203] [GtoPdb: 1797] [UniProtKB: P00533] | ||||||||
| ChEMBL | Inhibition of recombinant human N-terminal GST-tagged wild-type EGFR (695 to end residues) expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr)4:1 as substrate pretreated for 60 mins followed by substrate addition after 1 hr by ADP-Glo luminescence assay | B | 6.35 | pIC50 | 442 | nM | IC50 | Eur J Med Chem (2017) 131: 107-125 [PMID:28315597] |
| ChEMBL | Omnia Assay: Briefly, 10x stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λem485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to 30 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (minutes) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response, Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.). | B | 7 | pIC50 | <100 | nM | IC50 | US-11351168-B1. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2022) |
| ChEMBL | Omnia Assay: EGFR (WT) and EGFR (T790M/L858R): The Omnia Assay Protocol for potency assessment against EGFR is performed as described in Example 251 above except that the EGFR-WT- and EGFR T790M/L858R-modified optimized reagent conditions are:[EGFR-WT]=5 nM, [ATP]=15 mM, [Y12-Sox]=5 mM (ATP KMapp˜12 mM); and [EGFR-T790M/L858R]=3 nM, [ATP]=50 mM, [Y12-Sox]=5 mM (ATP KMapp˜45 mM). | B | 8 | pIC50 | <10 | nM | IC50 | US-9987276-B2. Substituted 2,4-diaminopyrimidines as kinase inhibitors (2018) |
| ChEMBL | Omnia Assay Protocol : Briefly, 10× stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λcm485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). | B | 8 | pIC50 | <10 | nM | IC50 | US-10596172-B2. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2020) |
| Bruton tyrosine kinase/Tyrosine-protein kinase BTK in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5251] [GtoPdb: 1948] [UniProtKB: Q06187] | ||||||||
| ChEMBL | Reversible inhibition of full length recombinant human N-terminal His tagged BKT expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr)4:1 as substrate pretreated for 2 to 60 mins followed by substrate addition after 1 hr by ADP-Glo luminescence assay | B | 7.68 | pKi | 20.7 | nM | Ki | Eur J Med Chem (2017) 131: 107-125 [PMID:28315597] |
| ChEMBL | Inhibition of BTK C481S mutant (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 30 mins in presence of ATP by Microfluidic chip based mobility shift assay | B | 6.04 | pIC50 | 908 | nM | IC50 | J Med Chem (2022) 65: 7415-7437 [PMID:35594541] |
| ChEMBL | Inhibition of BTK C481R mutant (unknown origin) expressed in baculovirus infected Trichoplusia ni pro cells incubated for 30 mins in presence of ATP by Microfluidic chip based mobility shift assay | B | 6.07 | pIC50 | 854 | nM | IC50 | J Med Chem (2022) 65: 7415-7437 [PMID:35594541] |
| ChEMBL | Omnia Assay: Briefly, 10x stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λem485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to 30 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (minutes) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response, Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.). | B | 7 | pIC50 | <100 | nM | IC50 | US-11351168-B1. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2022) |
| ChEMBL | Inhibition of BTK T474M mutant (unknown origin) expressed in baculovirus infected Trichoplusia ni pro cells incubated for 30 mins in presence of ATP by Microfluidic chip based mobility shift assay | B | 7.12 | pIC50 | 75 | nM | IC50 | J Med Chem (2022) 65: 7415-7437 [PMID:35594541] |
| ChEMBL | Inhibition of BTK (unknown origin) incubated for 40 mins by radiometric kinase assay | B | 7.27 | pIC50 | 54 | nM | IC50 | Eur J Med Chem (2023) 245: 114913-114913 [PMID:36399923] |
| ChEMBL | Inhibition of BTK T474I mutant (unknown origin) expressed in baculovirus infected Trichoplusia ni pro cells incubated for 30 mins in presence of ATP by Microfluidic chip based mobility shift assay | B | 7.32 | pIC50 | 48 | nM | IC50 | J Med Chem (2022) 65: 7415-7437 [PMID:35594541] |
| ChEMBL | Inhibition of BTK phosphorylation in human whole blood assessed as reduction in BTK phosphorylation incubated for 30 mins | B | 7.4 | pIC50 | 40 | nM | IC50 | J Med Chem (2022) 65: 1206-1224 [PMID:34734694] |
| ChEMBL | Inhibition of His-tagged full-length recombinant wild-type human BTK (Ala2 to Ser659 residues) expressed in baculovirus infected insect cells incubated for 30 mins in presence of ATP by Microfluidic chip based mobility shift assay | B | 7.66 | pIC50 | 22 | nM | IC50 | J Med Chem (2022) 65: 7415-7437 [PMID:35594541] |
| ChEMBL | Omnia Assay Protocol for Potency Assessment Against BTK: Briefly, 10× stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM 3-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λem485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to 30 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (minutes) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response, Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.). | B | 8 | pIC50 | <10 | nM | IC50 | US-10828300-B2. Substituted 2,4-diaminopyrimidines as kinase inhibitors (2020) |
| ChEMBL | Omnia Assay Protocol : Briefly, 10× stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λcm485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). | B | 8 | pIC50 | <10 | nM | IC50 | US-10596172-B2. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2020) |
| ChEMBL | Inhibition of recombinant human His-tagged full length BTK expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay | B | 8.01 | pIC50 | 9.8 | nM | IC50 | Bioorg Med Chem (2020) 28: 115236-115236 [PMID:31843459] |
| ChEMBL | Inhibition of full length recombinant human N-terminal His tagged BKT expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr)4:1 as substrate pretreated for 60 mins followed by substrate addition after 1 hr by ADP-Glo luminescence assay | B | 8.05 | pIC50 | 9 | nM | IC50 | Eur J Med Chem (2017) 131: 107-125 [PMID:28315597] |
| ChEMBL | Lanthscreen Eu Kinase Binding Assay : Lanthscreen Eu Kinase Binding assay for BMX is performed as described above for BTK except that 1 nM human recombinant full length TEC (His-tagged) kinase and 1 nM Alexa Fluor647-labeled Kinase Tracer #178 were used instead.Representative compounds of the present invention are assessed for inhibition of BTK, BMX, and TXK measuring phosphorylation of a substrate (Z′-LYTE assay, Life Technologies) and TEC measuring displacement of a tracer (Lanthscreen® Eu Kinase Binding assay, Life Technologies). | B | 8.21 | pIC50 | 6.1 | nM | IC50 | US-9975882-B2. Heteroaromatic compounds as BTK inhibitors (2018) |
| ChEMBL | Inhibition of BTK (unknown origin) | B | 8.34 | pIC50 | 4.61 | nM | IC50 | Bioorg Med Chem Lett (2016) 26: 1954-1957 [PMID:26976214] |
| ChEMBL | Inhibition of human recombinant full length BTK expressed in baculovirus in Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate incubated for 1 hr by ADP-Glo assay | B | 8.67 | pIC50 | 2.12 | nM | IC50 | Bioorg Med Chem (2019) 27: 4124-4142 [PMID:31395509] |
| ChEMBL | Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assay | B | 9 | pIC50 | 1 | nM | IC50 | J Med Chem (2022) 65: 1206-1224 [PMID:34734694] |
| ChEMBL | Inhibition of N-terminal His-tagged full length human recombinant BTK expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) peptide substrate incubated for 60 mins by ADP-Glo luminescence assay | B | 9.14 | pIC50 | 0.72 | nM | IC50 | Eur J Med Chem (2017) 126: 444-455 [PMID:27912175] |
| ChEMBL | Inhibition of human recombinant full-length N-terminal His-tagged BTK expressed in baculovirus infected Sf9 insect cells after 60 mins by ADP-Glo kinase assay | B | 9.14 | pIC50 | 0.72 | nM | IC50 | Eur J Med Chem (2017) 135: 60-69 [PMID:28432946] |
| ChEMBL | Inhibition of human recombinant full-length N-terminal His-tagged BTK expressed in baculovirus infected Sf9 insect cells measured after 60 mins by ADP-Glo kinase assay | B | 9.14 | pIC50 | 0.72 | nM | IC50 | Bioorg Med Chem (2017) 25: 765-772 [PMID:27956037] |
| ChEMBL | Irreversible inhibition of BTK (unknown origin) | B | 9.15 | pIC50 | 0.7 | nM | IC50 | Bioorg Med Chem (2021) 47: 116358-116358 [PMID:34479103] |
| ChEMBL | Inhibition of BTK (unknown origin) | B | 9.15 | pIC50 | 0.7 | nM | IC50 | Eur J Med Chem (2018) 151: 315-326 [PMID:29631132] |
| ChEMBL | Inhibition of recombinant full-length N-terminal His-tagged human BTK expressed in baculovirus infected Sf9 insect cells using Poly(4:1 Glu,Tyr) peptide substrate incubated for 60 mins by ADP-Glo luminescence assay | B | 9.22 | pIC50 | 0.6 | nM | IC50 | Eur J Med Chem (2018) 143: 1847-1857 [PMID:29146136] |
| ChEMBL | Inhibition of recombinant human N-terminal His-tagged BTK expressed in baculovirus infected sf9 cells using poly(4:1 Glu,Tyr) as substrate by ADP-Glo kinase assay | B | 9.22 | pIC50 | 0.6 | nM | IC50 | ACS Med Chem Lett (2016) 7: 1050-1055 [PMID:27994736] |
| GtoPdb | - | - | 9.3 | pIC50 | <0.5 | nM | IC50 | Clinical Development of AVL - 292: A Potent, Selective Covalent Btk Inhibitor for the Treatment of B Cell Malignancies.. http://www.celgene.com |
| ChEMBL | Inhibition of BTK (unknown origin) | B | 9.3 | pIC50 | 0.5 | nM | IC50 | Eur J Med Chem (2021) 218: 113356-113356 [PMID:33773287] |
| IL2 inducible T cell kinase/Tyrosine-protein kinase ITK/TSK in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2959] [GtoPdb: 2046] [UniProtKB: Q08881] | ||||||||
| ChEMBL | Omnia Assay: Briefly, 10x stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λem485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to 30 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (minutes) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response, Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.). | B | 6.26 | pIC50 | 550 | nM | IC50 | US-11351168-B1. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2022) |
| ChEMBL | Omnia Assay: ITK: This example describes continuous-read kinase assays to measure inherent potency of compound against active forms of ITK enzymes as described in Example 251 above except that the modified ITK-optimized reagent conditions are:[ITK]=10 nM, [ATP]=25 [Y6-Sox]=10 μM (ATP KMapp=33 μM). | B | 7.26 | pIC50 | 55 | nM | IC50 | US-9987276-B2. Substituted 2,4-diaminopyrimidines as kinase inhibitors (2018) |
| ChEMBL | Omnia Assay Protocol : Briefly, 10× stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λcm485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). | B | 7.26 | pIC50 | 55 | nM | IC50 | US-10596172-B2. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2020) |
| Janus kinase 1/Tyrosine-protein kinase JAK1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2835] [GtoPdb: 2047] [UniProtKB: P23458] | ||||||||
| ChEMBL | Inhibition of recombinant human N-terminal GST-tagged JAK1 (850 to 1154 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay | B | 6 | pIC50 | >1000 | nM | IC50 | Bioorg Med Chem (2020) 28: 115236-115236 [PMID:31843459] |
| Janus kinase 2/Tyrosine-protein kinase JAK2 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2971] [GtoPdb: 2048] [UniProtKB: O60674] | ||||||||
| ChEMBL | Inhibition of recombinant human N-terminal His-tagged JAK2 (826 to 1132 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay | B | 6.27 | pIC50 | 533.7 | nM | IC50 | Bioorg Med Chem (2020) 28: 115236-115236 [PMID:31843459] |
| Janus kinase 3/Tyrosine-protein kinase JAK3 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2148] [GtoPdb: 2049] [UniProtKB: P52333] | ||||||||
| ChEMBL | Inhibition of recombinant human N-terminal GST-tagged JAK3 (781 to end residues) expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr)4:1 as substrate pretreated for 60 mins followed by substrate addition after 1 hr by ADP-Glo luminescence assay | B | 5.76 | pIC50 | 1753 | nM | IC50 | Eur J Med Chem (2017) 131: 107-125 [PMID:28315597] |
| ChEMBL | Omnia Assay: Briefly, 10x stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λem485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). At the conclusion of each assay, progress curves from each well were examined for linear reaction kinetics and fit statistics (R2, 95% confidence interval, absolute sum of squares). Initial velocity (0 minutes to 30 minutes) from each reaction was determined from the slope of a plot of relative fluorescence units vs time (minutes) and then plotted against inhibitor concentration to estimate IC50 from log[Inhibitor] vs Response, Variable Slope model in GraphPad Prism from GraphPad Software (San Diego, Calif.). | B | 7 | pIC50 | <100 | nM | IC50 | US-11351168-B1. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2022) |
| ChEMBL | Inhibition of recombinant human N-terminal GST-tagged JAK3 (781 to end residues) expressed in baculovirus infected Sf9 cells using poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ADP-Glo kinase assay | B | 7.18 | pIC50 | 66.5 | nM | IC50 | Bioorg Med Chem (2020) 28: 115254-115254 [PMID:31866272] |
| ChEMBL | Inhibition of recombinant N-terminal GST-tagged human JAK3 (781 to end residues) expressed in baculovirus infected Sf9 insect cells using Poly(4:1 Glu,Tyr) peptide substrate incubated for 60 mins by ADP-Glo luminescence assay | B | 7.65 | pIC50 | 22.5 | nM | IC50 | Eur J Med Chem (2018) 143: 1847-1857 [PMID:29146136] |
| ChEMBL | Omnia Assay: JAK3: The Omnia Assay Protocol for potency assessment against JAK3 was performed in a substantially similar manner as that described in Example 251 above except that the modified JAK3-optimized reagent conditions were:[JAK3]=5 nM, [ATP]=5 μM, [Y12-Sox]=5 μM (ATP KMapp˜5 μM). | B | 8 | pIC50 | <10 | nM | IC50 | US-9987276-B2. Substituted 2,4-diaminopyrimidines as kinase inhibitors (2018) |
| ChEMBL | Omnia Assay Protocol : Briefly, 10× stocks of EGFR-WT (PV3872) from Invitrogen and EGFR-T790M/L858R (40350) from BPS Bioscience, San Diego, Calif., 1.13×ATP (AS001A) and appropriate Tyr-Sox conjugated peptide substrates (KCZ1001) were prepared in 1× kinase reaction buffer consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM β-glycerophosphate, 5% glycerol (10× stock, KB002A) and 0.2 mM DTT (DS001A). 5 μL of each enzyme were pre-incubated in a Corning (#3574) 384-well, white, non-binding surface microtiter plate (Corning, N.Y.) for 30 min. at 27° C. with a 0.5 μL volume of 50% DMSO and serially diluted compounds prepared in 50% DMSO. Kinase reactions were started with the addition of 45 μL of the ATP/Tyr-Sox peptide substrate mix and monitored every 30-90 seconds for 60 minutes at λex360/λcm485 in a Synergy4 plate reader from BioTek (Winooski, Vt.). | B | 8 | pIC50 | <10 | nM | IC50 | US-10596172-B2. 2,4-disubstituted pyrimidines useful as kinase inhibitors (2020) |
| ChEMBL | Inhibition of recombinant human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay | B | 8.07 | pIC50 | 8.5 | nM | IC50 | Bioorg Med Chem (2020) 28: 115236-115236 [PMID:31843459] |
| LYN proto-oncogene, Src family tyrosine kinase/Tyrosine-protein kinase Lyn in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3905] [GtoPdb: 2060] [UniProtKB: P07948] | ||||||||
| ChEMBL | Inhibition of LYN (unknown origin) | B | 5.36 | pIC50 | 4400 | nM | IC50 | Eur J Med Chem (2018) 151: 315-326 [PMID:29631132] |
| ChEMBL | Inhibition of LYN (unknown origin) | B | 5.36 | pIC50 | 4400 | nM | IC50 | Bioorg Med Chem (2021) 47: 116358-116358 [PMID:34479103] |
| tec protein tyrosine kinase/Tyrosine-protein kinase Tec in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4246] [GtoPdb: 2238] [UniProtKB: P42680] | ||||||||
| ChEMBL | Lanthscreen Eu Kinase Binding Assay : Lanthscreen Eu Kinase Binding assay for BMX is performed as described above for BTK except that 1 nM human recombinant full length TEC (His-tagged) kinase and 1 nM Alexa Fluor647-labeled Kinase Tracer #178 were used instead.Representative compounds of the present invention are assessed for inhibition of BTK, BMX, and TXK measuring phosphorylation of a substrate (Z′-LYTE assay, Life Technologies) and TEC measuring displacement of a tracer (Lanthscreen® Eu Kinase Binding assay, Life Technologies). | B | 8.17 | pIC50 | 6.8 | nM | IC50 | US-9975882-B2. Heteroaromatic compounds as BTK inhibitors (2018) |
| ChEMBL | Inhibition of TEC (unknown origin) | B | 8.21 | pIC50 | 6.2 | nM | IC50 | Eur J Med Chem (2018) 151: 315-326 [PMID:29631132] |
| ChEMBL | Inhibition of TEC (unknown origin) | B | 8.21 | pIC50 | 6.2 | nM | IC50 | Bioorg Med Chem (2021) 47: 116358-116358 [PMID:34479103] |
| TXK tyrosine kinase/Tyrosine-protein kinase TXK in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4367] [GtoPdb: 2268] [UniProtKB: P42681] | ||||||||
| ChEMBL | Lanthscreen Eu Kinase Binding Assay : Lanthscreen Eu Kinase Binding assay for BMX is performed as described above for BTK except that 1 nM human recombinant full length TEC (His-tagged) kinase and 1 nM Alexa Fluor647-labeled Kinase Tracer #178 were used instead.Representative compounds of the present invention are assessed for inhibition of BTK, BMX, and TXK measuring phosphorylation of a substrate (Z′-LYTE assay, Life Technologies) and TEC measuring displacement of a tracer (Lanthscreen® Eu Kinase Binding assay, Life Technologies). | B | 7.66 | pIC50 | 22 | nM | IC50 | US-9975882-B2. Heteroaromatic compounds as BTK inhibitors (2018) |
| YES proto-oncogene 1, Src family tyrosine kinase in Human [GtoPdb: 2284] [UniProtKB: P07947] | ||||||||
| GtoPdb | - | - | 6.14 | pIC50 | 723 | nM | IC50 | Clinical Development of AVL - 292: A Potent, Selective Covalent Btk Inhibitor for the Treatment of B Cell Malignancies.. http://www.celgene.com |
ChEMBL data shown on this page come from version 36:
Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]
