ENTOSPLETINIB

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Synonyms
Status
Molecule Category Free-form
UNII 6I3O3W6O3B

Structure

InChI Key XSMSNFMDVXXHGJ-UHFFFAOYSA-N
Smiles c1cn2cc(-c3ccc4cn[nH]c4c3)nc(Nc3ccc(N4CCOCC4)cc3)c2n1
InChI
InChI=1S/C23H21N7O/c1-2-17-14-25-28-20(17)13-16(1)21-15-30-8-7-24-23(30)22(27-21)26-18-3-5-19(6-4-18)29-9-11-31-12-10-29/h1-8,13-15H,9-12H2,(H,25,28)(H,26,27)

Physicochemical Descriptors

Property Name Value
Molecular Formula C23H21N7O
Molecular Weight 411.47
AlogP 3.85
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 4.0
Polar Surface Area 83.37
Molecular species NEUTRAL
Aromatic Rings 5.0
Heavy Atoms 31.0

Bioactivity

Mechanism of Action Action Reference
Tyrosine-protein kinase SYK inhibitor INHIBITOR PubMed
Protein: Tyrosine-protein kinase SYK
Description: Tyrosine-protein kinase SYK
Organism : Homo sapiens
P43405 ENSG00000165025
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakA family
453 - - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakB family
453 - - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase PDGFR family
327 - - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Syk family
2-367 8-19416 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Tec family
- 801 - - -
Assay Description Organism Bioactivity Reference
Inhibition of full length Syk (unknown origin) using biotinylated peptide substrate Homo sapiens 7.7 nM
Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay Homo sapiens 26.0 nM
Inhibition of Syk in goat antihuman IgE-induced CD63 expression in human whole blood by FACS analysis Homo sapiens 367.0 nM
Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation Homo sapiens 453.0 nM
Inhibition of cKit in stem cell factor-stimulated bone marrow derived mouse mast cells assessed as phosphorylation after 1 hr incubation Mus musculus 445.0 nM
Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry Homo sapiens 327.0 nM
Inhibition of Syk in alphaIgM-stimulated human B cells assessed as CD86 expression after 1 hr incubation by flow cytometry Homo sapiens 125.0 nM
Inhibition of Syk in alphaIgM-stimulated human B cells assessed as cell proliferation after 1 hr incubation by flow cytometry Homo sapiens 41.0 nM
Inhibition of Syk in immune complex-stimulated human monocyte assessed as TNFalpha production after 1 hr incubation Homo sapiens 147.0 nM
Antiinflammatory activity in po dosed Lewis rat collagen-induced arthritis model assessed as disease parameter measured as body weight treated twice daily on arthritic days 0 to 7 Rattus norvegicus 47.4 uM.hr
Antiinflammatory activity in po dosed Lewis rat collagen-induced arthritis model assessed as disease parameter measured as ankle diameter treated twice daily on arthritic days 0 to 7 Rattus norvegicus 20.0 uM.hr
Antiinflammatory activity in po dosed Lewis rat collagen-induced arthritis model assessed as disease parameter measured as paw weight treated twice daily on arthritic days 0 to 7 Rattus norvegicus 24.0 uM.hr
Antiinflammatory activity in po dosed Lewis rat collagen-induced arthritis model assessed as disease parameter measured as ankle inflammation treated twice daily on arthritic days 0 to 7 by histological analysis Rattus norvegicus 29.5 uM.hr
Antiinflammatory activity in po dosed Lewis rat collagen-induced arthritis model assessed as disease parameter measured as knee inflammation treated twice daily on arthritic days 0 to 7 by histological analysis Rattus norvegicus 9.8 uM.hr
Antiinflammatory activity in po dosed Lewis rat collagen-induced arthritis model assessed as disease parameter measured as peritosteal bone width treated twice daily on arthritic days 0 to 7 by histological analysis Rattus norvegicus 32.7 uM.hr
Inhibition of Syk (unknown origin) using 5-Fluo-Ahx-GAPDYENLQELNKK-Amide as substrate after 60 mins by microfluidic mobility shift assay Homo sapiens 377.0 nM
Cytotoxicity against C57BL/6 mouse bone marrow cells assessed as growth inhibition preincubated for 4 days followed by [3H]-thymidine addition measured after 5 hrs by betaplate counting analysis Mus musculus 582.0 nM
Inhibition of Syk in anti-igM stimulated human Ramos B cells assessed as phospho-BLNK level preincubated for 30 mins followed by anti-IgM stimulation measured after 15 mins by flow cytometric analysis Homo sapiens 878.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 0.47 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 14.2 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -5.807 %
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 0.79 % 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 0.02 % 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 0.79 % 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 0.02 %
Inhibition of SYK (unknown origin) using XL665-labeled peptide as substrate in presence of ATP measured after 30 mins by TR-FRET assay Homo sapiens 16.5 nM
Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay Homo sapiens 2.0 nM
Inhibition of SYK in human whole blood assessed as reduction in anti-FCepsilonR1 mAb-induced basophil activation by measuring decrease in CD63 surface expression incubated for 60 mins followed by anti-FCepsilonR1 mAb stimulation for 20 mins by flow cytometry analysis Homo sapiens 178.0 nM
Inhibition of SYK (unknown origin) using poly(Glu, Tyr) 4:1 as substrate incubated in presence of [gamma33P]ATP by image analyser Homo sapiens 82.0 nM
Inhibition of BTK (unknown origin) using poly(Glu, Tyr) 4:1 as substrate incubated in presence of [gamma33P]ATP by image analyser Homo sapiens 801.0 nM

Cross References

Resources Reference
ChEMBL CHEMBL3265032
DrugBank DB12121
FDA SRS 6I3O3W6O3B
Guide to Pharmacology 7889
PDB CG9
PubChem 59473233
SureChEMBL SCHEMBL2483776
ZINC ZINC000098208742
CONTENTS