BMS-986142

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Synonyms
Status
Molecule Category UNKNOWN
UNII PJX9GH268R

Structure

InChI Key ZRYMMWAJAFUANM-INIZCTEOSA-N
Smiles Cc1c(-c2c(F)cc(C(N)=O)c3[nH]c4c(c23)CC[C@H](C(C)(C)O)C4)cccc1-n1c(=O)c2cccc(F)c2n(C)c1=O
InChI
InChI=1S/C32H30F2N4O4/c1-15-17(7-6-10-24(15)38-30(40)19-8-5-9-21(33)28(19)37(4)31(38)41)25-22(34)14-20(29(35)39)27-26(25)18-12-11-16(32(2,3)42)13-23(18)36-27/h5-10,14,16,36,42H,11-13H2,1-4H3,(H2,35,39)/t16-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C32H30F2N4O4
Molecular Weight 572.61
AlogP 4.4
Hydrogen Bond Acceptor 6.0
Hydrogen Bond Donor 3.0
Number of Rotational Bond 4.0
Polar Surface Area 123.11
Molecular species NEUTRAL
Aromatic Rings 5.0
Heavy Atoms 42.0

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 Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C19
- 32200 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C8
- 2600 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C9
- 17100 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A4
- 8500 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Src family
- 71-3800 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Tec family
- 1-750 - - -
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel
- 5500 - - -
Assay Description Organism Bioactivity Reference
Inhibition of full length recombinant human His-tagged BTK expressed in baculovirus using fluoresceinated peptide incubated for 60 mins by fluorescent assay Homo sapiens 0.5 nM Inhibition of full length recombinant human His-tagged BTK expressed in baculovirus using fluoresceinated peptide incubated for 60 mins by fluorescent assay Homo sapiens 25.0 nM
Inhibition of BTK in human Ramos-B cells assessed as suppression of BCR/anti-IgG-stimulated Ca2+ flux after 1 hr incubation in dark by FLIPR1 assay Homo sapiens 9.0 nM Inhibition of BTK in human Ramos-B cells assessed as suppression of BCR/anti-IgG-stimulated Ca2+ flux after 1 hr incubation in dark by FLIPR1 assay Homo sapiens 750.0 nM
Inhibition of BTK in human whole blood assessed as suppression of BCR/anti-IgM/IgG-stimulated CD69 surface expression after 18 hrs with agitation by FITC-staining based FACS analysis Homo sapiens 90.0 nM
Inhibition of BTK in human peripheral B cells assessed as suppression of BCR/anti-IgM/IgG-stimulated cell proliferation Homo sapiens 3.0 nM
Inhibition of BTK in human peripheral B cells assessed as suppression of BCR/anti-IgM/IgG-stimulated CD86 surface expression Homo sapiens 4.0 nM
Inhibition of BTK in human PBM cells assessed as suppression of FCRgammaR/immune complex-stimulated TNFalpha production Homo sapiens 3.0 nM
Inhibition of ITK in human peripheral T cells assessed as suppression of TCR/anti-CD3-stimulated protein catalyzed PLCgamma1 phosphorylation Homo sapiens 410.0 nM
Inhibition of BTK in mouse whole blood assessed as suppression of BCR/anti-IgM/IgG-stimulated CD69 surface expression after 18 hrs with agitation by FITC-staining based FACS analysis Mus musculus 140.0 nM
Inhibition of BTK in human whole blood basophils assessed as suppression of FceRI/anti-IgE-stimulated CD63 surface expression Homo sapiens 89.0 nM
Inhibition of Na+ channel (unknown origin) at 10 uM at 1 Hz by patch clamp assay Homo sapiens 10.0 %
Inhibition of Na+ channel (unknown origin) at 10 uM at 4 Hz by patch clamp assay Homo sapiens 13.0 %
Inhibition of TEC (unknown origin) Homo sapiens 10.0 nM
Inhibition of ITK (unknown origin) Homo sapiens 15.0 nM
Inhibition of BLK (unknown origin) Homo sapiens 23.0 nM
Inhibition of TXK (unknown origin) Homo sapiens 28.0 nM
Inhibition of BMX (unknown origin) Homo sapiens 32.0 nM
Inhibition of LCK (unknown origin) Homo sapiens 71.0 nM
Inhibition of Ca2+ channel (unknown origin) at 10 uM by patch clamp assay Homo sapiens 40.0 %
Btk Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 μM), ATP (20 μM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Homo sapiens 0.54 nM
Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assay Homo sapiens 1.0 nM
Inhibition of BTK phosphorylation in human whole blood assessed as reduction in BTK phosphorylation incubated for 30 mins Homo sapiens 110.0 nM

Cross References

Resources Reference
ChEMBL CHEMBL3900554
DrugBank DB15291
FDA SRS PJX9GH268R
Guide to Pharmacology 9857
PDB 73T
PubChem 86582336
SureChEMBL SCHEMBL16319712
ZINC ZINC000222995022
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