BMS-911543

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Synonyms
Status
Molecule Category UNKNOWN
UNII 7N03P021J8
EPA CompTox DTXSID00155403

Structure

InChI Key JCINBYQJBYJGDM-UHFFFAOYSA-N
Smiles CCn1c(C(=O)N(C2CC2)C2CC2)cc2c3c(ncn3C)c(Nc3cc(C)n(C)n3)nc21
InChI
InChI=1S/C23H28N8O/c1-5-30-17(23(32)31(14-6-7-14)15-8-9-15)11-16-20-19(24-12-28(20)3)21(26-22(16)30)25-18-10-13(2)29(4)27-18/h10-12,14-15H,5-9H2,1-4H3,(H,25,26,27)

Physicochemical Descriptors

Property Name Value
Molecular Formula C23H28N8O
Molecular Weight 432.53
AlogP 3.5
Hydrogen Bond Acceptor 8.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 6.0
Polar Surface Area 85.8
Molecular species NEUTRAL
Aromatic Rings 4.0
Heavy Atoms 32.0

Bioactivity

Mechanism of Action Action Reference
Tyrosine-protein kinase JAK2 inhibitor INHIBITOR PubMed PubMed
Protein: Tyrosine-protein kinase JAK2
Description: Tyrosine-protein kinase JAK2
Organism : Homo sapiens
O60674 ENSG00000096968
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Cytochrome P450 Cytochrome P450 family 1 Cytochrome P450 family 1A Cytochrome P450 1A2
- 1000 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A4
- 3000 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakA family
- 1-80 1 360 -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase JakB family
- 1-80 1 360 -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4A
- 5600 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4B
- 5600 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4C
- 5600 - - -
Enzyme Phosphodiesterase Phosphodiesterase 4 Phosphodiesterase 4D
- 5600 - - -
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel
- - - - 20-20
Assay Description Organism Bioactivity Reference
Inhibition of recombinant JAK2 (unknown origin) using 5-FAM-KKKKEEIYFFFG-OH substrate and ATP incubated for 180 mins by scintillation counting method Homo sapiens 1.1 nM
Inhibition of recombinant JAK1 (unknown origin) using 5-FAM-KKKKEEIYFFFG-OH substrate and ATP incubated for 180 mins by scintillation counting method Homo sapiens 75.0 nM
Inhibition of recombinant JAK3 (unknown origin) using 5-FAM-KKKKEEIYFFFG-OH substrate and ATP incubated for 180 mins by scintillation counting method Homo sapiens 360.0 nM
Antiproliferative activity against human SET2 cells incubated for 72 hrs by [3H] thymidine incorporation assay Homo sapiens 60.0 nM
Inhibition of recombinant TYK2 (unknown origin) by scintillation counting method Homo sapiens 66.0 nM
Binding affinity to JAK1 (unknown origin) assessed as dissociation constant Homo sapiens 110.0 nM
Binding affinity to JAK2 (unknown origin) assessed as dissociation constant Homo sapiens 0.48 nM
Binding affinity to JAK3 (unknown origin) assessed as dissociation constant Homo sapiens 360.0 nM
Inhibition of human ERG channel at 30 uM Homo sapiens 20.0 %
Antiproliferative activity against mouse BAF3 cells expressing JAK2 V617F mutant incubated for 72 hrs by [3H] thymidine incorporation assay Mus musculus 70.0 nM
Inhibition of JAK2 in human SET2 cells assessed as reduction in STAT5 phosphorylation incubated for 2 hrs by Western blot method Homo sapiens 80.0 nM
Inhibition of JAK2 in mouse BAF3 cells assessed as reduction in STAT5 phosphorylation incubated for 2 hrs by Western blot method Mus musculus 65.0 nM
Inhibition of JAK1/JAK3 in T cells (unknown origin) assessed as reduction in IL2-mediated cell proliferation Homo sapiens 990.0 nM
Inhibition of JAK2 in mouse pharamcodynamic model assessed as reduction in STAT5 phosphorylation at 10 mg/kg, po measured up to 18 hrs Mus musculus 65.0 %
Inhibition of JAK2 in mouse pharamcodynamic model assessed as reduction in STAT5 phosphorylation at 5 mg/kg, po measured after 8 hrs Mus musculus 50.0 %
Inhibition of human ERG at 30 uM by patch clamp assay Homo sapiens 20.0 %
Inhibition of sodium channel (unknown origin) at 10 uM at 1 and 4 Hz stimulation by patch clamp assay Homo sapiens 10.0 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 12.48 %
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 -0.18 % 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 -0.18 %
Inhibition of recombinant human JAK1 (854 to 1154 residues) expressed in insect cells using Y1-B as substrate incubated for 30 mins by microfluidic mobility shift assay Homo sapiens 360.0 nM
Inhibition of JAK in human BEAS-2B cells assessed as reduction in IL13-induced STAT6 phosphorylation at 1 uM incubated for 1 hr followed by IL13 addition and measured after 15 mins by immunofluorescence assay relative to control Homo sapiens 50.0 %

Cross References

Resources Reference
ChEMBL CHEMBL3545215
DrugBank DB12591
FDA SRS 7N03P021J8
Guide to Pharmacology 7954
PDB 50V
PubChem 50922691
SureChEMBL SCHEMBL1512419
ZINC ZINC000100468481
CONTENTS