EVOBRUTINIB

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Synonyms
Status
Molecule Category UNKNOWN
UNII ZA45457L1K

Structure

InChI Key QUIWHXQETADMGN-UHFFFAOYSA-N
Smiles C=CC(=O)N1CCC(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChI
InChI=1S/C25H27N5O2/c1-2-22(31)30-14-12-18(13-15-30)16-27-25-23(24(26)28-17-29-25)19-8-10-21(11-9-19)32-20-6-4-3-5-7-20/h2-11,17-18H,1,12-16H2,(H3,26,27,28,29)

Physicochemical Descriptors

Property Name Value
Molecular Formula C25H27N5O2
Molecular Weight 429.52
AlogP 4.35
Hydrogen Bond Acceptor 6.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 7.0
Polar Surface Area 93.37
Molecular species NEUTRAL
Aromatic Rings 3.0
Heavy Atoms 32.0

Bioactivity

Mechanism of Action Action Reference
Tyrosine-protein kinase BTK inhibitor INHIBITOR PubMed Other PubMed
Protein: Tyrosine-protein kinase BTK
Description: Tyrosine-protein kinase BTK
Organism : Homo sapiens
Q06187 ENSG00000010671
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Adhesion
- 5840 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Alk family
- - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase EGFR family
- 38 5600 - 1
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakA family
- - - - 0
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakB family
- - - - 0
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Src family
- - - - 42
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Tec family
- 9-8600 16 - 30
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel
- - - 3100 -
Membrane receptor
- 5840 - - -
Assay Description Organism Bioactivity Reference
Inhibition of recombinant human cytoplasmic His-tagged ERBB2 expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 1.0 %
Inhibition of recombinant human full length His-tagged BTK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 90.0 %
Inhibition of cytoplasmic recombinant human full length His-tagged BMX expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 89.0 %
Inhibition of human full length GST-tagged TXK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 30.0 %
Inhibition of recombinant human full length His-tagged BLK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 42.0 %
Inhibition of recombinant human catalytic GST-tagged JAK3 expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 0.0 %
Inhibition of recombinant human cytoplasmic GST-tagged EGFR expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 1.0 %
Inhibition of recombinant human cytoplasmic GST-tagged LTK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens -2.0 %
Inhibition of recombinant human cytoplasmic GST-tagged ERBB4 expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 57.0 %
Inhibition of recombinant human cytoplasmic full length His-tagged TEC expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 80.0 %
Inhibition of cytoplasmic recombinant human full length His-tagged BMX expressed in baculovirus by Z'-LYTE assay Homo sapiens 37.9 nM
Inhibition of recombinant human cytoplasmic full length His-tagged TEC expressed in baculovirus by Z'-LYTE assay Homo sapiens 37.9 nM
Inhibition of recombinant human cytoplasmic GST-tagged ERBB4 expressed in baculovirus by Z'-LYTE assay Homo sapiens 37.9 nM
Inhibition of full-length human recombinant BTK using FITC-Ahx-TSELKKVVALYDYMPMNAND-NH2 as substrate measured after 60 mins by caliper assay Homo sapiens 62.0 nM
Inhibition of BTK in vitamin D3 differentiated human THP1 cells assessed as inhibition of FCgammaR-induced IL8 production measured after 24 hrs by HTRF assay Homo sapiens 61.0 nM
Inhibition of BTK in human B cells assessed as reduction in anti-IgM/IL4-stimulated CD69 expression on B cells preincubated for 60 mins followed by anti-IgM antibody/IL4 stimulation and measured after 16 hrs by flow cytometry Homo sapiens 320.0 nM
Binding affinity to DNA-tagged recombinant BTK (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis Homo sapiens 16.0 nM
Binding affinity to DNA-tagged recombinant BMX (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis Homo sapiens 31.0 nM
Binding affinity to DNA-tagged recombinant TEC (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis Homo sapiens 4.5 nM
Covalent inhibition of N-terminal GST-fused human BTK (2-659(end) amino acids) expressed in baculovirus expression system using FITC-AHA-EEPLYWSFPAKKK-NH2 as substrate incubated for 90 mins by microfluidic off-Chip Mobility Shift Assay Homo sapiens 8.9 nM
Inhibition of BTK in human PBMC cells assessed as reduction in anti-IgM-stimulated CD69 expression on B cells preincubated for 60 mins followed by goat F(ab')2 anti-human IgM stimulation and measured after overnight incubation by flow cytometry Homo sapiens 61.0 nM
Inhibition of B cell activation in C57BL/6 mouse at 1 mg/kg, po after 0.25 hr relative to control Mus musculus 17.0 %
Inhibition of B cell activation in C57BL/6 mouse at 1 mg/kg, po after 1 hr relative to control Mus musculus 71.0 %
Inhibition of B cell activation in C57BL/6 mouse at 1 mg/kg, po after 24 hr relative to control Mus musculus 25.0 %
Antiarthritic activity in po dosed Lewis mouse model of collagen-induced arthritis assessed as reduction in ankle histopathological scores administered via gavage once daily starting from day 6 to day 16 Mus musculus 5.18 mg kg-1
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 6.68 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.03 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.03 %
Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assay Homo sapiens 5.0 nM
Binding affinity to wild-type human full length BTK (M1 to S659 residues) expressed in mammalian expression system by Kinomescan method Homo sapiens 4.6 nM

Cross References

Resources Reference
ChEMBL CHEMBL4072833
DrugBank DB15170
FDA SRS ZA45457L1K
Guide to Pharmacology 9752
PDB MZJ
PubChem 71479709
SureChEMBL SCHEMBL14165673
ZINC ZINC000205623965
CONTENTS