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Compound Detail

CHEMBL3900554

BMS-986142
🧪 Phase II
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🧪 Phase II
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

Basic Information

ChEMBL ID CHEMBL3900554
Name BMS-986142
Phase Phase II
Structure Type MOL
InChI Key ZRYMMWAJAFUANM-INIZCTEOSA-N

Known Names

Bms-986142
16
Targets
40
Activities
1
Assay Types
30
PK Parameters
20
Publications
1
Known Names
2
Indications
1
Mechanisms

Molecular Properties

572.6
MW (Da)
4.40
ALogP
6
HBA
3
HBD
123.1
PSA (Ų)
0.30
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Unknown

Extended Properties

Molecular Formula C32H30F2N4O4
MW 572.61
Aromatic Rings 5
Heavy Atoms 42
NP-Likeness -0.25

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Tyrosine-protein kinase BTK inhibitor INHIBITOR Tyrosine-protein kinase BTK

Indications

Arthritis, Rheumatoid Osteoarthritis

Activity Summary

IC50 40 meas. best 9.39

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Tyrosine-protein kinase BTK
CHEMBL5251
IC50 9.39 8.4684 0.4 19
Tyrosine-protein kinase Tec
CHEMBL4246
IC50 8.0 8.0 10.0 1
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
IC50 7.82 7.105 15.0 2
Tyrosine-protein kinase Blk
CHEMBL2250
IC50 7.64 7.64 23.0 1
Tyrosine-protein kinase TXK
CHEMBL4367
IC50 7.55 7.55 28.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
IC50 7.5 7.5 32.0 1
Tyrosine-protein kinase Lck
CHEMBL258
IC50 7.15 6.285 71.0 2
Tyrosine-protein kinase BTK
CHEMBL3259478
IC50 6.85 6.85 140.0 1
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
IC50 5.96 5.96 1100.0 1
Early activation antigen CD69
CHEMBL3308911
IC50 5.89 5.89 1300.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 5.58 5.58 2600.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.26 5.26 5500.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.07 5.07 8500.0 1
Tyrosine-protein kinase JAK2
CHEMBL2971
IC50 4.89 4.578 13000.0 5
Cytochrome P450 2C9
CHEMBL3397
IC50 4.77 4.77 17100.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 4.49 4.49 32200.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 22331.79 ng.hr.mL-1 Mus musculus
AUC 22331.79 ng.hr.mL-1 Mus musculus
AUC 13170.03 ng.hr.mL-1 Rattus norvegicus
AUC 2863.05 ng.hr.mL-1 Macaca fascicularis
AUC 9161.76 ng.hr.mL-1 Canis lupus familiaris
CL 4.1 mL.min-1.kg-1 Mus musculus
CL 4.2 mL.min-1.kg-1 Rattus norvegicus
CL 10.0 mL.min-1.kg-1 Macaca fascicularis
CL 3.2 mL.min-1.kg-1 Canis lupus familiaris
Cmax 4900.0 nM Mus musculus
Cmax 4900.0 nM Mus musculus
Cmax 2300.0 nM Rattus norvegicus
Cmax 850.0 nM Macaca fascicularis
Cmax 1200.0 nM Canis lupus familiaris
F 4.0 % Mus musculus
F 93.0 % Mus musculus
F 67.0 % Rattus norvegicus
F 33.0 % Macaca fascicularis
F 100.0 % Canis lupus familiaris
MRT 4.8 hr Mus musculus
MRT 5.1 hr Rattus norvegicus
MRT 4.7 hr Macaca fascicularis
MRT 18.0 hr Canis lupus familiaris
T1/2 3.4 hr Mus musculus
T1/2 3.6 hr Rattus norvegicus
T1/2 5.1 hr Macaca fascicularis
T1/2 13.0 hr Canis lupus familiaris
Tmax 1.0 hr Mus musculus
Tmax 3.0 hr Rattus norvegicus
Tmax 3.7 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Tyrosine-protein kinase BTK IC50 = 0.41 nM 9.39 Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recom... -
Tyrosine-protein kinase BTK IC50 = 0.41 nM 9.39 Human Recombinant Btk Enzyme Assay: To V-bottom 384-well plates were added test ... -
Tyrosine-protein kinase BTK IC50 = 0.41 nM 9.39 Human Recombinant Btk Enzyme Assay: To V-bottom 384-well plates were added test ... -
Tyrosine-protein kinase BTK IC50 = 0.5 nM 9.3 Inhibition of full length recombinant human His-tagged BTK expressed in baculovi... 27583770
Tyrosine-protein kinase BTK IC50 = 0.54 nM 9.27 Btk Enzyme Assay: To V-bottom 384-well plates were added test compounds, human r... -
Tyrosine-protein kinase BTK IC50 = 0.54 nM 9.27 Human Recombinant Btk Enzyme Assay: To V-bottom 384-well plates were added test ... -
Tyrosine-protein kinase BTK IC50 = 0.54 nM 9.27 Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recom... -
Tyrosine-protein kinase BTK IC50 = 0.54 nM 9.27 Human Recombinant Btk Enzyme Assay: To V-bottom 384-well plates were added test ... -
Tyrosine-protein kinase BTK IC50 = 0.84 nM 9.08 Human Recombinant Btk Enzyme Assay: To V-bottom 384-well plates were added test ... -
Tyrosine-protein kinase BTK IC50 = 1.0 nM 9.0 Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate i... 34734694
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Inhibition of BTK in human PBM cells assessed as suppression of FCRgammaR/immune... 27583770
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Inhibition of BTK in human peripheral B cells assessed as suppression of BCR/ant... 27583770
Tyrosine-protein kinase BTK IC50 = 4.0 nM 8.4 Inhibition of BTK in human peripheral B cells assessed as suppression of BCR/ant... 27583770
Tyrosine-protein kinase BTK IC50 = 9.0 nM 8.05 Inhibition of BTK in human Ramos-B cells assessed as suppression of BCR/anti-IgG... 27583770
Tyrosine-protein kinase Tec IC50 = 10.0 nM 8.0 Inhibition of TEC (unknown origin) 27583770
Tyrosine-protein kinase ITK/TSK IC50 = 15.0 nM 7.82 Inhibition of ITK (unknown origin) 27583770
Tyrosine-protein kinase Blk IC50 = 23.0 nM 7.64 Inhibition of BLK (unknown origin) 27583770
Tyrosine-protein kinase BTK IC50 = 25.0 nM 7.6 Inhibition of full length recombinant human His-tagged BTK expressed in baculovi... 27583770
Tyrosine-protein kinase TXK IC50 = 28.0 nM 7.55 Inhibition of TXK (unknown origin) 27583770
Cytoplasmic tyrosine-protein kinase BMX IC50 = 32.0 nM 7.5 Inhibition of BMX (unknown origin) 27583770

Literature References

PubMed DOI Target Context # Activities
27583770 10.1021/acs.jmedchem.6b01088 ADMET 42
- 10.6019/CHEMBL5303304 Fibroblast 16
27583770 10.1021/acs.jmedchem.6b01088 Unchecked 14
27583770 10.1021/acs.jmedchem.6b01088 Tyrosine-protein kinase BTK 12
27583770 10.1021/acs.jmedchem.6b01088 NON-PROTEIN TARGET 12
- 10.6019/CHEMBL5303304 U2OS 10
- 10.6019/CHEMBL5303304 HEK-293T 8
27583770 10.1021/acs.jmedchem.6b01088 Molecular identity unknown 5
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
34734694 10.1021/acs.jmedchem.1c00926 Tyrosine-protein kinase BTK 2
27583770 10.1021/acs.jmedchem.6b01088 No relevant target 2
27583770 10.1021/acs.jmedchem.6b01088 Tyrosine-protein kinase Lck 2
27583770 10.1021/acs.jmedchem.6b01088 Tyrosine-protein kinase ITK/TSK 2
27583770 10.1021/acs.jmedchem.6b01088 Cytochrome P450 2C8 1
27583770 10.1021/acs.jmedchem.6b01088 Cytochrome P450 2C9 1
27583770 10.1021/acs.jmedchem.6b01088 Cytochrome P450 2C19 1
27583770 10.1021/acs.jmedchem.6b01088 Cytochrome P450 2D6 1
27583770 10.1021/acs.jmedchem.6b01088 Cytochrome P450 1A2 1
27583770 10.1021/acs.jmedchem.6b01088 Voltage-gated inwardly rectifying potassium channel KCNH2 1
27583770 10.1021/acs.jmedchem.6b01088 Tyrosine-protein kinase Blk 1

Data from ChEMBL 36 via Core Engine