FENEBRUTINIB

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Synonyms
Status
Molecule Category UNKNOWN
UNII E9L2885WUL

Structure

InChI Key WNEODWDFDXWOLU-QHCPKHFHSA-N
Smiles C[C@H]1CN(C2COC2)CCN1c1ccc(Nc2cc(-c3ccnc(N4CCn5c(cc6c5CC(C)(C)C6)C4=O)c3CO)cn(C)c2=O)nc1
InChI
InChI=1S/C37H44N8O4/c1-23-18-42(27-21-49-22-27)9-10-43(23)26-5-6-33(39-17-26)40-30-13-25(19-41(4)35(30)47)28-7-8-38-34(29(28)20-46)45-12-11-44-31(36(45)48)14-24-15-37(2,3)16-32(24)44/h5-8,13-14,17,19,23,27,46H,9-12,15-16,18,20-22H2,1-4H3,(H,39,40)/t23-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C37H44N8O4
Molecular Weight 664.81
AlogP 3.57
Hydrogen Bond Acceptor 11.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 7.0
Polar Surface Area 120.99
Molecular species NEUTRAL
Aromatic Rings 4.0
Heavy Atoms 49.0

Bioactivity

Mechanism of Action Action Reference
Tyrosine-protein kinase BTK inhibitor INHIBITOR PubMed 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(%)
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
- - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakA family
- - - - 5
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakB family
- - - - 5
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Src family
- - - - 6
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Tec family
- 1-31 - 1-13 23
Ion channel Voltage-gated ion channel Voltage-gated calcium channel
- - - - 2-4
Ion channel Voltage-gated ion channel Voltage-gated sodium channel
- - - - 1-2
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 BTK in human isolated primary B cells assessed as inhibition of anti-IgM-induced cell proliferation by [3H]thymidine incorporation assay Homo sapiens 1.2 nM
Inhibition of anti-IgM-induced BTK phosphorylation at Y233 in human whole blood after 6 hrs Homo sapiens 11.0 nM
Inhibition of human recombinant C-terminal polyhistidine tagged BTK (1 to 659 residues)-mediated synthetic peptide substrate phosphorylation expressed in baculovirus-infected insect cells Homo sapiens 0.91 nM
Inhibition of BTK in human whole blood-derived CD19+ B cells assessed as suppression of anti-IgM stimulated-CD69 expression preincubated for 1 hr followed by IgM stimulation for 18 hrs by FACS analysis Homo sapiens 8.0 nM
Inhibition of human Nav1.5 expressed in CHO cells at 1 uM incubated for 3 to 5 mins by Qpatch clamp assay Homo sapiens 0.6 %
Inhibition of human Nav1.5 expressed in CHO cells at 10 uM incubated for 3 to 5 mins by QPatch clamp assay Homo sapiens 1.9 %
Inhibition of human Cav1.2 expressed in CHO cells at 1 uM incubated for 3 to 5 mins by Qpatch clamp assay Homo sapiens 1.5 %
Inhibition of human Cav1.2 expressed in CHO cells at 10 uM incubated for 3 to 5 mins by Qpatch clamp assay Homo sapiens 3.8 %
Inhibition of recombinant human full length His-tagged BTK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 99.0 %
Inhibition of cytoplasmic recombinant human full length His-tagged BMX expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 56.0 %
Inhibition of human full length GST-tagged TXK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 4.0 %
Inhibition of recombinant human full length His-tagged BLK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 6.0 %
Inhibition of recombinant human catalytic GST-tagged JAK3 expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 5.0 %
Inhibition of recombinant human cytoplasmic GST-tagged EGFR expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens -7.0 %
Inhibition of recombinant human cytoplasmic GST-tagged LTK expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens -1.0 %
Inhibition of recombinant human cytoplasmic GST-tagged ERBB4 expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 1.0 %
Inhibition of recombinant human cytoplasmic full length His-tagged TEC expressed in baculovirus at 1 uM by Z'-LYTE assay Homo sapiens 23.0 %
Inhibition of BTK in human isolated primary B cells assessed as inhibition of CD40L-induced cell proliferation by [3H]thymidine incorporation assay Homo sapiens 1.4 nM
Inhibition of anti-IgM-induced BTK phosphorylation at Y233 in human primary B cells Homo sapiens 3.1 nM
Inhibition of BTK in human mononuclear cell-derived monocytes assessed as inhibition of FCgammaR3 activation-induced TNFalpha production by ELISA Homo sapiens 1.3 nM
Inhibition of BTK in human whole blood derived-basophils assessed as suppression of IgE mediated-FcepsilonR ligation-stimulated CD63 expression Homo sapiens 30.7 nM
Antiinflammatory activity in Lewis rat collagen-induced arthritis model assessed as reduction in ankle diameter AUC at 16 mg/kg, po administered qd for 16 days relative to control Rattus norvegicus 99.0 %
Antiinflammatory activity in Lewis rat collagen-induced arthritis model assessed as reduction in ankle diameter AUC at 4 mg/kg, po administered qd for 16 days relative to control Rattus norvegicus 89.0 %
Antiinflammatory activity in Lewis rat collagen-induced arthritis model assessed as reduction in ankle diameter AUC at 1 mg/kg, po administered qd for 16 days relative to control Rattus norvegicus 71.0 %
Antiinflammatory activity in Lewis rat collagen-induced arthritis model assessed as reduction in ankle diameter AUC at 0.25 mg/kg, po administered qd for 16 days relative to control Rattus norvegicus 26.0 %
Antiinflammatory activity in Lewis rat collagen-induced arthritis model assessed as reduction in ankle diameter AUC at 2 mg/kg, po administered bid for 16 days relative to control Rattus norvegicus 96.0 %
Antiinflammatory activity in Lewis rat collagen-induced arthritis model assessed as reduction in ankle diameter AUC at 0.5 mg/kg, po administered bid for 16 days relative to control Rattus norvegicus 79.0 %
Antiinflammatory activity in Lewis rat collagen-induced arthritis model assessed as reduction in ankle diameter AUC at 0.125 mg/kg, po administered bid for 16 days relative to control Rattus norvegicus 50.0 %
Inhibition of BTK C481S mutant (unknown origin) expressed in HEK293 cells Homo sapiens 1.6 nM
Inhibition of BTK C481R mutant (unknown origin) expressed in HEK293 cells Homo sapiens 1.3 nM
Inhibition of BTK T474I mutant (unknown origin) expressed in HEK293 cells Homo sapiens 12.6 nM
Inhibition of BTK T474M mutant (unknown origin) expressed in HEK293 cells Homo sapiens 3.4 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 17.31 %
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 -0.1 % 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 -0.1 %
Inhibition of BTK in human whole blood assessed as reduction in autophosphorylation at Y223 residue incubated for 1 hr by mesoscale assay Homo sapiens 2.3 nM
Inhibition of BTK in human whole blood assessed as reduction in anti-IgM-stimulated CD69 expression preincubated for 1 hr followed by goat F(ab')2 anti-human IgM stimulation and measured after 18 hrs by FACS analysis Homo sapiens 8.0 nM

Cross References

Resources Reference
ChEMBL CHEMBL4065122
DrugBank DB14785
FDA SRS E9L2885WUL
Guide to Pharmacology 9299
PDB 9AJ
PubChem 86567195
SureChEMBL SCHEMBL14912882
ZINC ZINC000220197997
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