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Compound Detail

CHEMBL3707348

ACALABRUTINIB
💊 Approved Drug
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💊 Approved Drug
CC#CC(=O)N1CCC[C@H]1c1nc(-c2ccc(C(=O)Nc3ccccn3)cc2)c2c(N)nccn12

Basic Information

ChEMBL ID CHEMBL3707348
Name ACALABRUTINIB
Phase Approved
Structure Type MOL
InChI Key WDENQIQQYWYTPO-IBGZPJMESA-N
Therapeutic ✓ Yes

Known Names

Acalabrutinib Acp-196
15
Targets
69
Activities
3
Assay Types
30
PK Parameters
20
Publications
2
Known Names
20
Indications
1
Mechanisms

Molecular Properties

465.5
MW (Da)
3.31
ALogP
7
HBA
2
HBD
118.5
PSA (Ų)
0.45
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2017
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product
USAN Stem -tinib
USAN Year 2016

Extended Properties

Molecular Formula C26H23N7O2
MW 465.52
Aromatic Rings 4
Heavy Atoms 35
NP-Likeness -0.95

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 Lymphoma, Large B-Cell, Diffuse Severe Acute Respiratory Syndrome Arthritis, Rheumatoid Bronchiolitis Obliterans Syndrome Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Food Hypersensitivity Hematologic Neoplasms Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Non-Hodgkin Ovarian Neoplasms Pancreatic Neoplasms Waldenstrom Macroglobulinemia Communicable Diseases Glioblastoma

ATC Classification

L01EL02
acalabrutinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 50 meas. best 10.85
Kd 16 meas. best 8.59
EC50 3 meas. best 8.1

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
TMD8
CHEMBL4296503
IC50 10.85 9.235 0.0 2
Tyrosine-protein kinase BTK
CHEMBL5251
Kd 8.59 8.135 2.6 2
Tyrosine-protein kinase BTK
CHEMBL5251
IC50 8.52 7.7896 3.0 24
Tyrosine-protein kinase Tec
CHEMBL4246
Kd 8.26 8.055 5.5 2
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
Kd 8.13 7.295 7.4 2
Unchecked
CHEMBL612545
EC50 8.1 8.1 8.0 1
Tyrosine-protein kinase BTK
CHEMBL5251
EC50 8.04 8.04 9.2 1
Rec1
CHEMBL4483266
IC50 7.89 7.89 13.0 1
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
IC50 7.8 7.8 16.0 3
Tyrosine-protein kinase Blk
CHEMBL2250
Kd 7.75 7.75 18.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
Kd 7.72 6.965 19.0 2
Tyrosine-protein kinase Tec
CHEMBL4246
IC50 7.7 7.1517 20.0 6
Tyrosine-protein kinase TXK
CHEMBL4367
Kd 7.62 7.62 24.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
IC50 7.34 7.06 46.0 4
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
Kd 7.22 7.035 60.0 2
Epidermal growth factor receptor
CHEMBL203
Kd 6.77 6.01 170.0 2
Tyrosine-protein kinase TXK
CHEMBL4367
IC50 6.43 6.1475 368.0 4
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
IC50 6.0 6.0 1000.0 2
Platelet glycoprotein VI
CHEMBL3308912
IC50 5.92 5.92 1210.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
Kd 5.52 5.52 3000.0 1
Epidermal growth factor receptor
CHEMBL203
IC50 5.45 5.45 3513.0 1
Epidermal growth factor receptor
CHEMBL203
EC50 5.33 5.33 4700.0 1
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
Kd 4.92 4.92 12000.0 1
Ramos
CHEMBL614629
IC50 4.5 4.5 31300.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 584.0 ng.hr.mL-1 Homo sapiens
AUC 1140.0 ng.hr.mL-1 Homo sapiens
AUC 826.0 ng.hr.mL-1 Homo sapiens
AUC 1990.0 ng.hr.mL-1 Homo sapiens
AUC 1730.0 ng.hr.mL-1 Homo sapiens
AUC 602.0 ng.hr.mL-1 Homo sapiens
AUC 1160.0 ng.hr.mL-1 Homo sapiens
AUC 926.0 ng.hr.mL-1 Homo sapiens
AUC 2310.0 ng.hr.mL-1 Homo sapiens
AUC 1850.0 ng.hr.mL-1 Homo sapiens
AUC 603.0 ng.hr.mL-1 Homo sapiens
AUC 1160.0 ng.hr.mL-1 Homo sapiens
AUC 1850.0 ng.hr.mL-1 Homo sapiens
AUC 2310.0 ng.hr.mL-1 Homo sapiens
AUC 1870.0 ng.hr.mL-1 Homo sapiens
AUC 603.0 ng.hr.mL-1 Homo sapiens
AUC 1160.0 ng.hr.mL-1 Homo sapiens
AUC 927.0 ng.hr.mL-1 Homo sapiens
AUC 2310.0 ng.hr.mL-1 Homo sapiens
AUC 1870.0 ng.hr.mL-1 Homo sapiens
Cmax 780.0 nM Mus musculus
Cmax 1136.36 nM Homo sapiens
Cmax 1729.25 nM Homo sapiens
Cmax 1776.51 nM Homo sapiens
Cmax 2899.98 nM Homo sapiens
Cmax 1937.62 nM Homo sapiens
T1/2 5.5 hr -
T1/2 1.16 hr Homo sapiens
T1/2 1.02 hr Homo sapiens
T1/2 1.13 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
TMD8 IC50 = 0.014 nM 10.85 Antiproliferative activity against human TMD8 cells assessed as reduction in cel... 33740548
Tyrosine-protein kinase BTK Kd = 2.6 nM 8.59 Binding affinity to BTK (unknown origin) assessed as dissociation constant by KI... 35041943
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Inhibition of BTK (unknown origin) 29631132
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Inhibition of BTK (unknown origin) 30939001
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Inhibition of BTK (unknown origin) 36561076
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Irreversible inhibition of recombinant human BTK 33773287
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Irreversible inhibition of BTK (unknown origin) 34479103
Tyrosine-protein kinase BTK IC50 = 3.0 nM 8.52 Inhibition of BTK (unknown origin) 37210838
Tyrosine-protein kinase BTK IC50 = 3.1 nM 8.51 Inhibition of recombinant BTK (unknown origin) preincubated for 1 hr followed by... 27210433
Tyrosine-protein kinase BTK IC50 = 3.1 nM 8.51 Inhibition of His-tagged recombinant human His-tagged full length BTK expressed ... 32527559
Tyrosine-protein kinase BTK IC50 = 5.1 nM 8.29 Inhibition of BTK (unknown origin) 35439421
Tyrosine-protein kinase BTK IC50 = 5.1 nM 8.29 Affinity Biochemical interaction (IMAP (immobilized metal ion affinity-based flu... -
Tyrosine-protein kinase BTK IC50 = 5.1 nM 8.29 Inhibition of human BTK by ATP-Competition Binding Assay 27903679
Tyrosine-protein kinase BTK IC50 = 5.1 nM 8.29 Inhibition of recombinant BTK (unknown origin) preincubated for 1 hr in presence... 26641137
Tyrosine-protein kinase Tec Kd = 5.5 nM 8.26 Binding affinity to TEC (unknown origin) assessed as dissociation constant by KI... 35041943
Receptor tyrosine-protein kinase erbB-2 Kd = 7.4 nM 8.13 Binding affinity to DNA-tagged recombinant ERBB2 (unknown origin) measured after... 32083858
Unchecked EC50 = 8.0 nM 8.1 Inhibition of human whole blood CD69 B cell activation 37801827
Tyrosine-protein kinase BTK EC50 = 9.2 nM 8.04 Inhibition of BTK in human whole blood 35439421
Tyrosine-protein kinase BTK IC50 = 11.0 nM 7.96 Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubat... 36912866
Rec1 IC50 = 13.0 nM 7.89 Antiproliferative activity against human REC-1 cells assessed as reduction in ce... 34672559

Literature References

PubMed DOI Target Context # Activities
26641137 10.1056/nejmoa1509981 ADMET 52
27903679 10.1158/1078-0432.ccr-16-0463 Unchecked 16
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
27903679 10.1158/1078-0432.ccr-16-0463 Epidermal growth factor receptor 11
33091850 10.1016/j.bmc.2020.115815 SUD4 10
- 10.6019/CHEMBL4689842 U2OS 10
- 10.6019/CHEMBL4689842 HEK-293T 10
33091850 10.1016/j.bmc.2020.115815 OCI-Ly10 10
- 10.6019/CHEMBL4689842 Fibroblast 10
27903679 10.1158/1078-0432.ccr-16-0463 Tyrosine-protein kinase BTK 9
35041943 10.1016/j.bmcl.2022.128549 Unchecked 9
27903679 10.1158/1078-0432.ccr-16-0463 Tyrosine-protein kinase ABL1 9
32083858 10.1021/acs.jmedchem.9b01916 Unchecked 7
26641137 10.1056/nejmoa1509981 Tyrosine-protein kinase BTK 7
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
27903679 10.1158/1078-0432.ccr-16-0463 Mast/stem cell growth factor receptor Kit 6
32083858 10.1021/acs.jmedchem.9b01916 Tyrosine-protein kinase BTK 6
27903679 10.1158/1078-0432.ccr-16-0463 Receptor-type tyrosine-protein kinase FLT3 6
34672559 10.1021/acs.jmedchem.1c01559 Unchecked 4

Data from ChEMBL 36 via Core Engine