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Compound Detail

CHEMBL3936761

ZANUBRUTINIB
💊 Approved Drug
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💊 Approved Drug
C=CC(=O)N1CCC([C@@H]2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn32)CC1

Basic Information

ChEMBL ID CHEMBL3936761
Name ZANUBRUTINIB
Phase Approved
Structure Type MOL
InChI Key RNOAOAWBMHREKO-QFIPXVFZSA-N
Therapeutic ✓ Yes

Known Names

Bgb-3111 Brukinsa Zanubrutinib
24
Targets
89
Activities
3
Assay Types
15
PK Parameters
20
Publications
3
Known Names
20
Indications
1
Mechanisms

Molecular Properties

471.6
MW (Da)
4.22
ALogP
6
HBA
2
HBD
102.5
PSA (Ų)
0.52
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2019
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral
USAN Stem -tinib
USAN Year 2018

Extended Properties

Molecular Formula C27H29N5O3
MW 471.56
Aromatic Rings 3
Heavy Atoms 35
NP-Likeness -0.59

Mechanism of Action

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

Indications

Lymphoma, Mantle-Cell Neoplasms Neoplasms Waldenstrom Macroglobulinemia Leukemia, Lymphocytic, Chronic, B-Cell Lymphohistiocytosis, Hemophagocytic Lymphoma, Follicular Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Anemia, Hemolytic, Autoimmune Castleman Disease Immunoglobulin G4-Related Disease Kidney Diseases Leukemia, Lymphoid Lupus Nephritis Lymphoma Lymphoma, B-Cell, Marginal Zone Neuromyelitis Optica Paraproteinemias

ATC Classification

L01EL03
zanubrutinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 77 meas. best 9.52
Kd 10 meas. best 8.34
EC50 2 meas. best 8.62

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Tyrosine-protein kinase BTK
CHEMBL5251
IC50 9.52 8.8871 0.3 17
OCI-Ly10
CHEMBL4483285
IC50 9.46 9.46 0.3 1
Rec1
CHEMBL4483266
IC50 9.44 9.44 0.4 2
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
IC50 9.21 8.214 0.6 5
Tyrosine-protein kinase Blk
CHEMBL2250
IC50 8.95 8.1133 1.1 3
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
IC50 8.8 8.0133 1.6 3
Tyrosine-protein kinase Tec
CHEMBL4246
IC50 8.77 7.8183 1.7 6
Tyrosine-protein kinase BTK
CHEMBL5251
EC50 8.62 8.62 2.4 1
Epidermal growth factor receptor
CHEMBL203
IC50 8.62 7.7933 2.4 9
Tyrosine-protein kinase TXK
CHEMBL4367
IC50 8.53 7.8333 3.0 3
TMD8
CHEMBL4296503
IC50 8.42 8.42 3.8 1
Tyrosine-protein kinase BTK
CHEMBL5251
Kd 8.34 8.34 4.6 1
Tyrosine-protein kinase Tec
CHEMBL4246
Kd 7.75 7.75 18.0 1
Protein-tyrosine kinase 6
CHEMBL4601
IC50 7.48 7.48 33.0 2
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
IC50 7.3 6.6557 50.0 7
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
Kd 7.21 7.21 61.0 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
Kd 7.12 7.12 76.0 1
Tyrosine-protein kinase Fgr
CHEMBL4454
IC50 6.81 6.81 155.0 2
Tyrosine-protein kinase Lck
CHEMBL258
IC50 6.73 6.73 187.0 2
Tyrosine-protein kinase FRK
CHEMBL4223
IC50 6.42 6.42 379.0 2
Epidermal growth factor receptor
CHEMBL203
EC50 6.41 6.41 390.0 1
Platelet glycoprotein VI
CHEMBL3308912
IC50 6.29 6.29 510.0 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
IC50 6.28 6.28 530.0 2
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 6.24 6.24 580.0 2
Tyrosine-protein kinase TXK
CHEMBL4367
Kd 6.01 6.01 980.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
Kd 5.8 5.8 1600.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 5.4 5.4 4000.0 1
Epidermal growth factor receptor
CHEMBL203
Kd 5.36 5.36 4400.0 1
MOLM-13
CHEMBL3706572
IC50 5.29 5.29 5095.0 1
Tyrosine-protein kinase Blk
CHEMBL2250
Kd 5.26 5.26 5500.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.24 5.24 5700.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 5.12 5.12 7600.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 4.84 4.53 14300.0 2
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
Kd 4.52 4.52 30000.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
Kd 4.52 4.52 30000.0 1
HEK-293T
CHEMBL3706568
IC50 4.41 4.41 39136.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 257.0 ng.hr.mL-1 Rattus norvegicus
CL 76.8 mL.min-1.kg-1 Rattus norvegicus
CL 109.0 mL.min-1.g-1 Homo sapiens
CL 25.6 mL.min-1.g-1 Canis lupus familiaris
CL 148.0 mL.min-1.g-1 Rattus norvegicus
CL 67.0 mL.min-1.g-1 Mus musculus
Cmax 498.35 nM Rattus norvegicus
Cmax 4800.0 nM Mus musculus
F 23.6 % Rattus norvegicus
Fu 0.051 - Mus musculus
Fu 0.058 - Homo sapiens
Fu 0.067 - Canis lupus familiaris
Fu 0.033 - Rattus norvegicus
T1/2 0.53 hr Rattus norvegicus
Tmax 0.33 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Tyrosine-protein kinase BTK IC50 = 0.3 nM 9.52 Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) ... 31381333
Tyrosine-protein kinase BTK IC50 = 0.3 nM 9.52 Inhibition of BTK (unknown origin) 33539089
Tyrosine-protein kinase BTK IC50 = 0.3 nM 9.52 Affinity Biochemical interaction (33P-ATP and filter-binding assay (Reaction Bio... -
Tyrosine-protein kinase BTK IC50 = 0.3 nM 9.52 Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) ... 36912866
Tyrosine-protein kinase BTK IC50 = 0.33 nM 9.48 Kinase Assay: Compounds disclosed herein were tested for inhibition of Btk kinas... -
OCI-Ly10 IC50 = 0.35 nM 9.46 Antiproliferative activity against human OCI-LY10 cells after 6 days by Celltite... 31381333
Rec1 IC50 = 0.36 nM 9.44 Antiproliferative activity against human Rec1 cells after 6 days by Celltiter-gl... 31381333
Rec1 IC50 = 0.36 nM 9.44 Antiproliferative activity against human REC1 cells assessed as reduction in cel... 36912866
Tyrosine-protein kinase BTK IC50 = 0.5 nM 9.3 Inhibition of BTK (unknown origin) 36561076
Tyrosine-protein kinase BTK IC50 = 0.5 nM 9.3 Inhibition of BTK (unknown origin) 35439421
Cytoplasmic tyrosine-protein kinase BMX IC50 = 0.62 nM 9.21 Inhibition of human BMX using poly[Glu:Tyr] (4:1) as substrate preincubated for ... 31381333
Cytoplasmic tyrosine-protein kinase BMX IC50 = 0.62 nM 9.21 Affinity Biochemical interaction (33P-ATP and filter-binding assay (Reaction Bio... -
Tyrosine-protein kinase BTK IC50 = 0.92 nM 9.04 Inhibition of human BTK using poly[Glu:Tyr] (4:1) as substrate preincubated for ... 31381333
Tyrosine-protein kinase Blk IC50 = 1.13 nM 8.95 Affinity Biochemical interaction (33P-ATP and filter-binding assay (Reaction Bio... -
Tyrosine-protein kinase Blk IC50 = 1.13 nM 8.95 Inhibition of human BLK using poly[Glu:Tyr] (4:1) as substrate preincubated for ... 31381333
Receptor tyrosine-protein kinase erbB-4 IC50 = 1.58 nM 8.8 Inhibition of human HER4 using poly[Glu:Tyr] (4:1) as substrate preincubated for... 31381333
Receptor tyrosine-protein kinase erbB-4 IC50 = 1.58 nM 8.8 Affinity Biochemical interaction (33P-ATP and filter-binding assay (Reaction Bio... -
Tyrosine-protein kinase Tec IC50 = 1.7 nM 8.77 Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate ... 36912866
Tyrosine-protein kinase BTK IC50 = 1.8 nM 8.74 Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubat... 36912866
Tyrosine-protein kinase BTK IC50 = 1.8 nM 8.74 Inhibition of BTK (unknown origin) 36439976

Literature References

PubMed DOI Target Context # Activities
31381333 10.1021/acs.jmedchem.9b00687 ADMET 27
31381333 10.1021/acs.jmedchem.9b00687 Mus musculus 20
31381333 10.1021/acs.jmedchem.9b00687 Unchecked 16
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL4689842 Fibroblast 10
34391034 10.1016/j.ejmech.2021.113724 TMD8 9
35041943 10.1016/j.bmcl.2022.128549 Unchecked 9
- 10.6019/CHEMBL4689842 U2OS 9
- 10.6019/CHEMBL4689842 HEK-293T 8
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
31381333 10.1021/acs.jmedchem.9b00687 Tyrosine-protein kinase BTK 5
31381333 10.1021/acs.jmedchem.9b00687 OCI-Ly10 3
34391034 10.1016/j.ejmech.2021.113724 Unchecked 3
34672559 10.1021/acs.jmedchem.1c01559 Unchecked 3
31381333 10.1021/acs.jmedchem.9b00687 Tyrosine-protein kinase ITK/TSK 2
31381333 10.1021/acs.jmedchem.9b00687 Tyrosine-protein kinase Tec 2
35099969 10.1021/acs.jmedchem.1c02208 Unchecked 2
31381333 10.1021/acs.jmedchem.9b00687 Tyrosine-protein kinase Lck 2
35439421 10.1021/acs.jmedchem.1c02134 Tyrosine-protein kinase BTK 2

Data from ChEMBL 36 via Core Engine