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Compound Detail

CHEMBL2110732

DACOMITINIB ANHYDROUS
💊 Approved Drug
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💊 Approved Drug
COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/CN1CCCCC1

Basic Information

ChEMBL ID CHEMBL2110732
Name DACOMITINIB ANHYDROUS
Phase Approved
Structure Type MOL
InChI Key LVXJQMNHJWSHET-AATRIKPKSA-N
Therapeutic ✓ Yes

Known Names

Dacomitinib anhydrous Pf-00299804
25
Targets
99
Activities
3
Assay Types
29
PK Parameters
20
Publications
2
Known Names
16
Indications
3
Mechanisms

Molecular Properties

469.9
MW (Da)
5.16
ALogP
6
HBA
2
HBD
79.4
PSA (Ų)
0.47
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2018
Availability Prescription
Chirality Achiral

Routes of Administration

Oral
USAN Stem -tinib
USAN Year 2010

Extended Properties

Molecular Formula C24H25ClFN5O2
MW 469.95
Aromatic Rings 3
Heavy Atoms 33
NP-Likeness -1.61

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Epidermal growth factor receptor erbB1 inhibitor INHIBITOR Epidermal growth factor receptor
Receptor protein-tyrosine kinase erbB-2 inhibitor INHIBITOR Receptor tyrosine-protein kinase erbB-2
Receptor protein-tyrosine kinase erbB-4 inhibitor INHIBITOR Receptor tyrosine-protein kinase erbB-4

Indications

Carcinoma, Non-Small-Cell Lung Lung Neoplasms Brain Neoplasms Brain Neoplasms Carcinoma Carcinoma, Squamous Cell Carcinoma, Squamous Cell Glioblastoma Head and Neck Neoplasms Neoplasms Neoplasms Penile Neoplasms Colorectal Neoplasms Liver Diseases Mouth Neoplasms Neoplasm Metastasis

Activity Summary

IC50 92 meas. best 9.2
Kd 4 meas. best 8.3
EC50 3 meas. best 7.66

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Epidermal growth factor receptor
CHEMBL203
IC50 9.2 8.1238 0.6 21
BaF3
CHEMBL614524
IC50 8.92 7.62 1.2 13
PC-9
CHEMBL614102
IC50 8.7 8.7 2.0 1
HCC827
CHEMBL4296422
IC50 8.7 8.1138 2.0 8
HCC4006
CHEMBL4523575
IC50 8.4 8.4 4.0 1
Epidermal growth factor receptor
CHEMBL203
Kd 8.3 8.3 5.0 1
Epidermal growth factor receptor
CHEMBL3608
IC50 8.24 7.97 5.8 2
NCI-H3255
CHEMBL4296476
IC50 8.15 6.95 7.0 5
SK-BR-3
CHEMBL613834
IC50 7.82 7.82 15.0 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
IC50 7.78 7.3963 16.7 8
BT-474
CHEMBL614529
IC50 7.75 7.75 18.0 1
Epidermal growth factor receptor
CHEMBL203
EC50 7.66 7.53 22.0 2
Unchecked
CHEMBL612545
IC50 7.54 6.5763 29.0 8
Unchecked
CHEMBL612545
EC50 7.54 7.54 29.0 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL2311234
IC50 7.39 7.39 41.0 1
Calu-3
CHEMBL614534
IC50 7.2 7.2 63.0 1
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
IC50 7.13 7.1175 73.7 4
A-431
CHEMBL614069
IC50 7.1 6.405 79.4 2
Tyrosine-protein kinase Lck
CHEMBL258
IC50 7.03 7.03 94.0 2
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
IC50 6.96 6.96 110.0 2
Cyclin-G-associated kinase
CHEMBL4355
Kd 6.78 6.78 168.0 1
HEK293
CHEMBL614818
IC50 6.73 6.73 185.0 1
NCI-H1975
CHEMBL614348
IC50 6.36 6.2933 440.0 3
A549
CHEMBL392
IC50 6.31 6.31 490.0 1
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
Kd 6.0 6.0 988.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 5.45 5.45 3566.0 2
Receptor-interacting serine/threonine-protein kinase 3
CHEMBL1795199
Kd 5.44 5.44 3637.0 1
NCI-H441
CHEMBL1075542
IC50 5.4 5.4 4000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 20500.0 ng.hr.mL-1 Rattus norvegicus
AUC 25200.0 ng.hr.mL-1 Canis lupus familiaris
AUC 5400.0 ng.hr.mL-1 Macaca fascicularis
AUC 2100.0 ng.hr.mL-1 Rattus norvegicus
AUC 3400.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1900.0 ng.hr.mL-1 Macaca fascicularis
CL 9.77 uL.min-1.(10^6cells)-1 Rattus norvegicus
CL 3.0 uL.min-1.(10^6cells)-1 Homo sapiens
CL 49.1 mL.min-1.kg-1 Rattus norvegicus
CL 24.4 mL.min-1.kg-1 Canis lupus familiaris
CL 44.1 mL.min-1.kg-1 Macaca fascicularis
Cmax 1340.57 nM Rattus norvegicus
Cmax 1851.26 nM Canis lupus familiaris
Cmax 468.13 nM Macaca fascicularis
F 80.0 % Rattus norvegicus
F 74.0 % Canis lupus familiaris
F 56.0 % Macaca fascicularis
T1/2 0.8217 hr -
T1/2 0.6667 hr Rattus norvegicus
T1/2 0.6667 hr Homo sapiens
T1/2 2.383 hr Rattus norvegicus
T1/2 4.15 hr Homo sapiens
T1/2 19.4 hr Rattus norvegicus
T1/2 20.9 hr Canis lupus familiaris
T1/2 12.1 hr Macaca fascicularis
T1/2 9.8 hr Rattus norvegicus
T1/2 15.9 hr Canis lupus familiaris
T1/2 5.7 hr Macaca fascicularis
T1/2 59.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Epidermal growth factor receptor IC50 = 0.63 nM 9.2 Inhibition of EGFR exon 19 deletion activating mutant phosphorylation in human P... 23930994
BaF3 IC50 = 1.2 nM 8.92 Cytotoxicity against mouse BaF3 cells harboring EGFR vIII mutant assessed as inh... 18089823
BaF3 IC50 = 1.4 nM 8.85 Cytotoxicity against mouse BaF3 cells harboring EGFR Del E746_S752InsV mutant as... 18089823
BaF3 IC50 = 1.6 nM 8.8 Cytotoxicity against mouse BaF3 cells harboring EGFR Del L747_A750InsP mutant as... 18089823
Epidermal growth factor receptor IC50 = 1.8 nM 8.74 Inhibition of EGFR (unknown origin) by ELISA method 26310890
BaF3 IC50 = 1.9 nM 8.72 Cytotoxicity against mouse BaF3 cells harboring EGFR Del L747_P753InsS mutant as... 18089823
HCC827 IC50 = 2.0 nM 8.7 Antiproliferative activity against human HCC827 cells harboring EGFR Del E746_A7... 18089823
PC-9 IC50 = 2.0 nM 8.7 Antiproliferative activity against human PC-9 cells harboring EGFR Del E746_A750... 18089823
BaF3 IC50 = 2.0 nM 8.7 Cytotoxicity against mouse BaF3 cells harboring EGFR Del S752_I759 mutant assess... 18089823
HCC827 IC50 = 2.0 nM 8.7 Antiproliferative activity against human HCC827 cells harboring EGFR Del E746_A7... 18089823
HCC827 IC50 = 2.0 nM 8.7 Antiproliferative activity against human HCC827 cells harboring EGFR Del E746_A7... 18089823
BaF3 IC50 = 2.6 nM 8.59 Cytotoxicity against mouse BaF3 cells harboring EGFR L858R mutant assessed as in... 18089823
HCC827 IC50 = 3.0 nM 8.52 Antiproliferative activity against human HCC827 cells harboring EGFR Del E746_A7... 18089823
HCC4006 IC50 = 4.0 nM 8.4 Antiproliferative activity against human HCC4006 cells harboring EGFR Del L747_E... 18089823
Epidermal growth factor receptor Kd = 5.0 nM 8.3 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878
Epidermal growth factor receptor IC50 = 5.8 nM 8.24 Inhibition of EGFR expressed in mouse NIH3T3 cells 18089823
Epidermal growth factor receptor IC50 = 6.0 nM 8.22 Inhibition of EGFR phosphorylation (unknown origin) 35439421
Epidermal growth factor receptor IC50 = 6.0 nM 8.22 Inhibition of GST-tagged EGFR (unknown origin) expressed in insect cells by ELIS... 33540357
Epidermal growth factor receptor IC50 = 6.0 nM 8.22 Inhibition of EGFR (unknown origin) 33771586
Epidermal growth factor receptor IC50 = 6.0 nM 8.22 Inhibition of EGFR (unknown origin) 32828424

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 Fibroblast 261
- 10.6019/CHEMBL4689842 HEK-293T 260
- 10.6019/CHEMBL4689842 U2OS 260
27491023 10.1021/acs.jmedchem.6b00883 ADMET 29
18089823 10.1158/0008-5472.can-07-1885 Unchecked 19
18089823 10.1158/0008-5472.can-07-1885 BaF3 14
18089823 10.1158/0008-5472.can-07-1885 Epidermal growth factor receptor 9
18089823 10.1158/0008-5472.can-07-1885 Receptor tyrosine-protein kinase erbB-2 9
18089823 10.1158/0008-5472.can-07-1885 HCC827 9
18089823 10.1158/0008-5472.can-07-1885 NCI-H3255 6
29191878 10.1126/science.aan4368 Unchecked 5
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
- 10.6019/CHEMBL3301361 No relevant target 4
23930994 10.1021/jm400822z Epidermal growth factor receptor 4
35439421 10.1021/acs.jmedchem.1c02134 Epidermal growth factor receptor 3
27491023 10.1021/acs.jmedchem.6b00883 Epidermal growth factor receptor 3
37468498 10.1038/s41467-023-40064-9 Nuclear receptor subfamily 1 group I member 2 3
37499291 10.1016/j.ejmech.2023.115671 Epidermal growth factor receptor 3
- 10.6019/CHEMBL3301361 ADMET 3
37647129 10.1021/acs.jmedchem.3c00845 Epidermal growth factor receptor 3

Data from ChEMBL 36 via Core Engine