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Compound Detail

CHEMBL1873475

IBRUTINIB
💊 Approved Drug
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💊 Approved Drug
C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1

Basic Information

ChEMBL ID CHEMBL1873475
Name IBRUTINIB
Phase Approved
Structure Type MOL
InChI Key XYFPWWZEPKGCCK-GOSISDBHSA-N
Therapeutic ✓ Yes

Known Names

CRA-032765 Ibrutinib Imbruvica PC-32765 PCI 32765 PCI-32765 PCI-32765-00
90
Targets
557
Activities
4
Assay Types
30
PK Parameters
20
Publications
7
Known Names
20
Indications
1
Mechanisms

Molecular Properties

440.5
MW (Da)
4.22
ALogP
7
HBA
1
HBD
99.2
PSA (Ų)
0.47
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2013
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product First in Class
USAN Stem -tinib
USAN Year 2011

Extended Properties

Molecular Formula C25H24N6O2
MW 440.51
Aromatic Rings 4
Heavy Atoms 33
NP-Likeness -0.80

Mechanism of Action

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

Indications

Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Mantle-Cell Neoplasms Neoplasms Waldenstrom Macroglobulinemia Waldenstrom Macroglobulinemia Bronchiolitis Obliterans Syndrome Graft vs Host Disease Lymphoma Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Amyloidosis Anaphylaxis Anemia, Hemolytic, Autoimmune Burkitt Lymphoma Carcinoid Tumor Carcinoma, Non-Small-Cell Lung

ATC Classification

L01EL01
ibrutinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 497 meas. best 11.0
Kd 42 meas. best 9.25
EC50 9 meas. best 8.3
Ki 9 meas. best 9.62

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
TMD8
CHEMBL4296503
IC50 11.0 8.6817 0.0 6
Tyrosine-protein kinase BTK
CHEMBL5251
IC50 10.1 8.7105 0.1 127
Tyrosine-protein kinase Blk
CHEMBL2250
IC50 10.0 9.4462 0.1 13
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
IC50 10.0 8.8847 0.1 15
Tyrosine-protein kinase BTK
CHEMBL5251
Ki 9.62 8.264 0.2 5
OCI-Ly10
CHEMBL4483285
IC50 9.52 7.9933 0.3 6
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
IC50 9.4 9.0056 0.4 16
Epidermal growth factor receptor
CHEMBL203
IC50 9.3 8.0595 0.5 39
Tyrosine-protein kinase Tec
CHEMBL4246
IC50 9.3 8.1293 0.5 14
Tyrosine-protein kinase Blk
CHEMBL2250
Kd 9.25 9.25 0.6 1
Tyrosine-protein kinase TXK
CHEMBL4367
Kd 9.21 9.21 0.6 1
Tyrosine-protein kinase BTK
CHEMBL5251
Kd 9.19 8.6367 0.6 3
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
Kd 9.12 9.02 0.8 2
Rec1
CHEMBL4483266
IC50 9.1 7.53 0.8 2
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
Kd 9.04 8.83 0.9 2
Tyrosine-protein kinase Tec
CHEMBL4246
Kd 9.0 8.4567 1.0 3
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
Kd 8.85 8.825 1.4 2
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
IC50 8.82 7.9642 1.5 12
Tyrosine-protein kinase Fgr
CHEMBL4454
IC50 8.74 8.54 1.8 6
Tyrosine-protein kinase Lck
CHEMBL258
IC50 8.7 8.5291 2.0 11
Tyrosine-protein kinase TXK
CHEMBL4367
IC50 8.7 8.6167 2.0 6
Tyrosine-protein kinase CSK
CHEMBL2634
IC50 8.66 8.3475 2.2 4
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
IC50 8.57 7.7839 2.7 23
Protein-tyrosine kinase 6
CHEMBL4601
IC50 8.48 8.2367 3.3 3
Tyrosine-protein kinase HCK
CHEMBL3234
IC50 8.43 7.8486 3.7 7
Epidermal growth factor receptor
CHEMBL203
Kd 8.41 7.98 3.9 3
Tyrosine-protein kinase Yes
CHEMBL2073
IC50 8.39 8.24 4.1 4
Tyrosine-protein kinase BTK
CHEMBL5251
EC50 8.3 8.27 5.0 2
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
IC50 8.28 7.7167 5.2 3
Nuclear receptor subfamily 4 group A member 3
CHEMBL1961792
IC50 8.24 7.675 5.7 2
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 8.1 7.6606 8.0 18
Unchecked
CHEMBL612545
IC50 8.1 6.6413 8.0 16
Z-138
CHEMBL4483276
IC50 8.01 5.9333 9.7 3
Ramos
CHEMBL614629
IC50 8.0 5.582 10.0 20
Tyrosine-protein kinase Lyn
CHEMBL3905
Ki 7.85 7.85 14.0 1
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
IC50 7.8 7.1488 15.9 8
Tyrosine-protein kinase Lyn
CHEMBL3905
IC50 7.79 7.23 16.2 6
Tyrosine-protein kinase JAK3
CHEMBL2148
Kd 7.68 7.555 21.0 2
DOHH-2
CHEMBL2366181
IC50 7.64 7.14 23.0 3
Tyrosine-protein kinase Yes
CHEMBL2073
Kd 7.57 7.57 27.0 1
Tyrosine-protein kinase Fyn
CHEMBL1841
IC50 7.54 7.15 29.0 4
Tyrosine-protein kinase FRK
CHEMBL4223
IC50 7.54 7.32 29.2 2
MDA-MB-468
CHEMBL614335
IC50 7.52 7.52 30.0 1
Protein-tyrosine kinase 6
CHEMBL4601
Kd 7.51 7.51 31.0 1
HCC827
CHEMBL4296422
IC50 7.41 7.41 39.0 1
Tyrosine-protein kinase HCK
CHEMBL3234
Kd 7.38 7.38 42.0 1
Epidermal growth factor receptor
CHEMBL203
EC50 7.31 7.235 49.0 2
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
Kd 7.24 7.22 57.0 2
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
Kd 7.24 7.24 57.0 1
NCI-H522
CHEMBL614387
IC50 7.22 7.22 60.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 57.0 ng.hr.mL-1 Rattus norvegicus
AUC 26.0 ng.hr.mL-1 Mus musculus
AUC 21.4 ng.hr.mL-1 Mus musculus
AUC 643.0 ng.hr.mL-1 Rattus norvegicus
AUC 318.0 ng.hr.mL-1 Rattus norvegicus
AUC 628.0 ng.hr.mL-1 Mus musculus
AUC 11176.44 ng.hr.mL-1 Rattus norvegicus
AUC 11690.99 ng.hr.mL-1 Rattus norvegicus
CL 150.0 mL.min-1.g-1 Homo sapiens
CL 1980.0 mL.min-1.g-1 Mus musculus
CL 420.0 mL.min-1.g-1 Homo sapiens
CL 1020.0 mL.min-1.kg-1 Rattus norvegicus
CL 35.0 mL.min-1.kg-1 Rattus norvegicus
CL 28.33 mL.min-1.kg-1 Mus musculus
CL 920.0 mL.min-1.g-1 Homo sapiens
CL 1000.0 mL.min-1.g-1 Mus musculus
CL 330.0 mL.min-1.g-1 Rattus norvegicus
CL 846.7 mL.min-1.g-1 Homo sapiens
CL 762.0 mL.min-1.kg-1 Homo sapiens
CL 234.0 mL.min-1.g-1 Homo sapiens
CL 1000.0 mL.min-1.g-1 Mus musculus
CL 254.2 mL.min-1.g-1 Homo sapiens
CL 53200.0 mL.min-1.g-1 Rattus norvegicus
CL 27400.0 mL.min-1.g-1 Mus musculus
CL 846.7 mL.min-1.g-1 Homo sapiens
CL 0.005833 mL.min-1.kg-1 Rattus norvegicus
Cmax 88.53 nM Rattus norvegicus
Cmax 55.3 nM Mus musculus
Cmax 340.51 nM Rattus norvegicus
Cmax 7861.34 nM Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
TMD8 IC50 = 0.01 nM 11.0 Antiproliferative activity against human TMD8 cells assessed as reduction in cel... 33740548
Tyrosine-protein kinase BTK IC50 = 0.08 nM 10.1 Inhibition of recombinant human BTK using fluoresceinated peptide as substrate a... 30893553
Receptor tyrosine-protein kinase erbB-4 IC50 = 0.1 nM 10.0 In Vitro HotSpot Kinase Assay: IC50s were determined using the in vitro HotSpot ... -
Receptor tyrosine-protein kinase erbB-4 IC50 = 0.1 nM 10.0 HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase as... -
Tyrosine-protein kinase Blk IC50 = 0.1 nM 10.0 Inhibition of recombinant BLK (unknown origin) preincubated for 1 hr in presence... 26641137
Tyrosine-protein kinase BTK IC50 = 0.1 nM 10.0 Covalent inhibition of full length N-terminal GST tagged BTK (2 to 659 residues)... 39119945
Tyrosine-protein kinase Blk IC50 = 0.1 nM 10.0 Inhibition of BLK (unknown origin) incubated for 1 hr in presence of ATP by Z'LY... 36923918
Tyrosine-protein kinase Blk IC50 = 0.1 nM 10.0 Inhibition of BLK (unknown origin) 34839996
Tyrosine-protein kinase Blk IC50 = 0.1 nM 10.0 Inhibition of recombinant full length human His-tagged BLK cytoplasmic domain ex... 32527559
Tyrosine-protein kinase BTK IC50 = 0.1 nM 10.0 Inhibition of full-length human His-tagged BTK expressed in baculovirus expressi... 30655951
Receptor tyrosine-protein kinase erbB-4 IC50 = 0.1 nM 10.0 In Vitro HotSpot Kinase Assay: IC50s were determined using the in vitro HotSpot ... -
Receptor tyrosine-protein kinase erbB-4 IC50 = 0.1 nM 10.0 HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase as... -
Tyrosine-protein kinase BTK IC50 = 0.11 nM 9.96 Inhibition of human BTK using KVEKIGEGTYGVVYK as substrate preincubated for 20 m... 28945083
Tyrosine-protein kinase BTK IC50 = 0.2 nM 9.7 Inhibition of BTK (unknown origin) measured by ADP-Glo assay 35939993
Tyrosine-protein kinase BTK IC50 = 0.2 nM 9.7 Inhibition of recombinant human full length N-terminal GST-tagged BTK (2 to 659 ... 30290988
Tyrosine-protein kinase BTK IC50 = 0.2 nM 9.7 Inhibition of human full length BTK using FITC-AHA-EEPLYWSFPAKKK-NH2 as substrat... 30122225
Tyrosine-protein kinase BTK IC50 = 0.21 nM 9.68 Inhibition Activity Assay: The kinase activity was measured using QuickScout Scr... -
Tyrosine-protein kinase BTK IC50 = 0.21 nM 9.68 Inhibition of BTK (unknown origin) 30343954
Tyrosine-protein kinase Blk IC50 = 0.23 nM 9.64 Inhibition of human BLK using poly[Glu:Tyr] (4:1) as substrate preincubated for ... 31381333
Tyrosine-protein kinase BTK Ki = 0.24 nM 9.62 Binding affinity to BTK (unknown origin) assessed as inhibition constant measure... 38321747

Literature References

Data from ChEMBL 36 via Core Engine