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Compound Detail

CHEMBL4483575

REMIBRUTINIB
🧪 Phase III
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🧪 Phase III
C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C

Basic Information

ChEMBL ID CHEMBL4483575
Name REMIBRUTINIB
Phase Phase III
Structure Type MOL
InChI Key CUABMPOJOBCXJI-UHFFFAOYSA-N

Known Names

LOU064-NXA NVP-LOU064-NXA Remibrutinib
14
Targets
26
Activities
2
Assay Types
19
PK Parameters
20
Publications
3
Known Names
6
Indications

Molecular Properties

507.5
MW (Da)
4.47
ALogP
6
HBA
2
HBD
110.4
PSA (Ų)
0.41
QED
1
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral
USAN Stem -tinib
USAN Year 2021

Extended Properties

Molecular Formula C27H27F2N5O3
MW 507.54
Aromatic Rings 3
Heavy Atoms 37
NP-Likeness -1.10

Indications

Chronic Urticaria Immune System Diseases Multiple Sclerosis Hypersensitivity Sjogren's Syndrome Liver Diseases

ATC Classification

L04AA60
remibrutinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: IMMUNOSUPPRESSANTS

Activity Summary

IC50 13 meas. best 9.0
Kd 13 meas. best 9.62

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Tyrosine-protein kinase BTK
CHEMBL5251
Kd 9.62 9.41 0.2 2
Tyrosine-protein kinase BTK
CHEMBL5251
IC50 9.0 8.5922 1.0 9
Unchecked
CHEMBL612545
IC50 7.44 7.44 36.0 1
Tyrosine-protein kinase Tec
CHEMBL4246
Kd 7.11 7.035 77.0 2
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
Kd 6.27 6.115 540.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.85 5.85 1400.0 1
Phosphatidylinositol 4-kinase beta
CHEMBL3268
IC50 5.51 5.51 3100.0 1
Bile salt export pump
CHEMBL6020
IC50 5.18 5.18 6600.0 1
Tyrosine-protein kinase TXK
CHEMBL4367
Kd 4.77 4.77 17000.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
Kd 4.72 4.72 19000.0 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
Kd 4.52 4.52 30000.0 1
Epidermal growth factor receptor
CHEMBL203
Kd 4.52 4.52 30000.0 1
Tyrosine-protein kinase Blk
CHEMBL2250
Kd 4.52 4.52 30000.0 1
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
Kd 4.52 4.52 30000.0 1
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
Kd 4.52 4.52 30000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 33.0 mL.min-1.g-1 Rattus norvegicus
CL 325.0 mL.min-1.g-1 Mus musculus
CL 146.0 mL.min-1.g-1 Canis lupus familiaris
CL 44.0 mL.min-1.kg-1 Rattus norvegicus
CL 97.0 mL.min-1.kg-1 Mus musculus
CL 29.0 mL.min-1.kg-1 Canis lupus familiaris
CL 214.0 mL.min-1.kg-1 Rattus norvegicus
CL 80.0 mL.min-1.kg-1 Homo sapiens
CL 97.0 mL.min-1.kg-1 Rattus norvegicus
F 29.0 % Rattus norvegicus
F 16.0 % Mus musculus
F 5.0 % Canis lupus familiaris
T1/2 2.0 hr Homo sapiens
T1/2 0.5 hr Rattus norvegicus
T1/2 1.0 hr Mus musculus
T1/2 0.9 hr Canis lupus familiaris
Tmax 0.3 hr Rattus norvegicus
Tmax 0.3 hr Mus musculus
Tmax 0.8 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Tyrosine-protein kinase BTK Kd = 0.24 nM 9.62 Binding affinity to BTK (unknown origin) assessed as dissociation constant by KI... 35041943
Tyrosine-protein kinase BTK Kd = 0.63 nM 9.2 Binding affinity to DNA-tagged recombinant BTK (unknown origin) measured after 1... 32083858
Tyrosine-protein kinase BTK IC50 = 1.0 nM 9.0 Inhibition of Btk Enzymatic Activity: The inhibitory activity of the present com... -
Tyrosine-protein kinase BTK IC50 = 1.0 nM 9.0 Inhibition of Btk Enzymatic Activity Assay: The inhibitory activity of the prese... -
Tyrosine-protein kinase BTK IC50 = 1.0 nM 9.0 Biochemical Enzyme Assay: The inhibitory activity of the present compounds again... -
Tyrosine-protein kinase BTK IC50 = 1.0 nM 9.0 Enzymatic Activity Assay: The inhibitory activity of the present compounds again... -
Tyrosine-protein kinase BTK IC50 = 1.2 nM 8.92 Inhibition of BTK (unknown origin) 35041943
Tyrosine-protein kinase BTK IC50 = 1.3 nM 8.89 Inhibition of full-length human recombinant BTK using FITC-Ahx-TSELKKVVALYDYMPMN... 32083858
Tyrosine-protein kinase BTK IC50 = 2.5 nM 8.6 Inhibition of BTK in vitamin D3 differentiated human THP1 cells assessed as inhi... 32083858
Tyrosine-protein kinase BTK IC50 = 18.0 nM 7.75 Inhibition of BTK in human B cells assessed as reduction in anti-IgM/IL4-stimula... 32083858
Unchecked IC50 = 36.0 nM 7.44 Inhibition of CD69 expression on CD19 positive B cells in anti-IgD stimulated hu... 35041943
Tyrosine-protein kinase BTK IC50 = 67.0 nM 7.17 Inhibition of BTK in human basophils assessed as reduction in anti-IgE mouse IgG... 32083858
Tyrosine-protein kinase Tec Kd = 77.0 nM 7.11 Binding affinity to TEC (unknown origin) assessed as dissociation constant by KI... 35041943
Tyrosine-protein kinase Tec Kd = 110.0 nM 6.96 Binding affinity to DNA-tagged recombinant TEC (unknown origin) measured after 1... 32083858
Cytoplasmic tyrosine-protein kinase BMX Kd = 540.0 nM 6.27 Binding affinity to DNA-tagged recombinant BMX (unknown origin) measured after 1... 32083858
Cytoplasmic tyrosine-protein kinase BMX Kd = 1100.0 nM 5.96 Binding affinity to BMX (unknown origin) assessed as dissociation constant by KI... 35041943
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1400.0 nM 5.85 Inhibition of human ERG by Qpatch clamp method 32083858
Phosphatidylinositol 4-kinase beta IC50 = 3100.0 nM 5.51 Inhibition of PIK4CB (unknown origin) 32083858
Bile salt export pump IC50 = 6600.0 nM 5.18 Inhibition of BSEP (unknown origin) 32083858
Tyrosine-protein kinase TXK Kd = 17000.0 nM 4.77 Binding affinity to TXK (unknown origin) assessed as dissociation constant by KI... 35041943

Literature References

PubMed DOI Target Context # Activities
32083858 10.1021/acs.jmedchem.9b01916 Unchecked 100
32083858 10.1021/acs.jmedchem.9b01916 ADMET 35
32083858 10.1021/acs.jmedchem.9b01916 Rattus norvegicus 17
32083858 10.1021/acs.jmedchem.9b01916 Tyrosine-protein kinase BTK 16
32083858 10.1021/acs.jmedchem.9b01916 No relevant target 5
32083858 10.1021/acs.jmedchem.9b01916 Glutamate NMDA receptor 4
35041943 10.1016/j.bmcl.2022.128549 ADMET 3
35041943 10.1016/j.bmcl.2022.128549 Tyrosine-protein kinase BTK 3
32083858 10.1021/acs.jmedchem.9b01916 Nuclear receptor subfamily 1 group I member 2 2
32083858 10.1021/acs.jmedchem.9b01916 Tyrosine-protein kinase Tec 2
32083858 10.1021/acs.jmedchem.9b01916 Cytoplasmic tyrosine-protein kinase BMX 2
32083858 10.1021/acs.jmedchem.9b01916 Epidermal growth factor receptor 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
35041943 10.1016/j.bmcl.2022.128549 Tyrosine-protein kinase TXK 1
32083858 10.1021/acs.jmedchem.9b01916 Tyrosine-protein kinase ITK/TSK 1
32083858 10.1021/acs.jmedchem.9b01916 Receptor tyrosine-protein kinase erbB-2 1
32083858 10.1021/acs.jmedchem.9b01916 Receptor tyrosine-protein kinase erbB-4 1
32083858 10.1021/acs.jmedchem.9b01916 Cytochrome P450 3A4 1
32083858 10.1021/acs.jmedchem.9b01916 Sodium channel protein type 5 subunit alpha 1
32083858 10.1021/acs.jmedchem.9b01916 Voltage-dependent L-type calcium channel subunit alpha-1C 1

Data from ChEMBL 36 via Core Engine