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Compound Detail

CHEMBL3353410

OSIMERTINIB
💊 Approved Drug
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💊 Approved Drug
C=CC(=O)Nc1cc(Nc2nccc(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C

Basic Information

ChEMBL ID CHEMBL3353410
Name OSIMERTINIB
Phase Approved
Structure Type MOL
InChI Key DUYJMQONPNNFPI-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Azd-9291 AZD-9291 FREE BASE AZD9291 Mereletinib Osimertinib Tagrisso
54
Targets
654
Activities
4
Assay Types
30
PK Parameters
20
Publications
6
Known Names
12
Indications
1
Mechanisms

Molecular Properties

499.6
MW (Da)
4.51
ALogP
8
HBA
2
HBD
87.5
PSA (Ų)
0.31
QED
0
Ro5 Violations
10
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2015
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Natural Product
USAN Stem -tinib
USAN Year 2015

Extended Properties

Molecular Formula C28H33N7O2
MW 499.62
Aromatic Rings 4
Heavy Atoms 37
NP-Likeness -1.11

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Epidermal growth factor receptor erbB1 inhibitor INHIBITOR Epidermal growth factor receptor

Indications

Neoplasms Neoplasms Carcinoma, Non-Small-Cell Lung Lung Neoplasms Lung Neoplasms Adenocarcinoma Adenocarcinoma of Lung Carcinoma Carcinoma, Squamous Cell Colorectal Neoplasms Glioblastoma Brain Neoplasms

ATC Classification

L01EB04
osimertinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 594 meas. best 10.96
EC50 37 meas. best 8.7
Ki 17 meas. best 8.82
Kd 6 meas. best 7.92

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
PC-9
CHEMBL614102
IC50 10.96 7.3865 0.0 23
NCI-H1975
CHEMBL614348
IC50 10.96 7.2267 0.0 69
Epidermal growth factor receptor
CHEMBL203
IC50 10.7 7.8158 0.0 225
Unchecked
CHEMBL612545
IC50 9.46 6.8608 0.3 60
NCI-H292
CHEMBL614733
IC50 9.03 6.8375 0.9 4
HCC827
CHEMBL4296422
IC50 9.01 8.0326 1.0 23
von Hippel-Lindau disease tumor suppressor/EGFR
CHEMBL4523998
IC50 9.0 8.76 1.0 2
Epidermal growth factor receptor
CHEMBL203
Ki 8.82 7.9465 1.5 17
A549
CHEMBL392
IC50 8.81 6.1197 1.6 29
BaF3
CHEMBL614524
IC50 8.7 6.6468 2.0 47
Epidermal growth factor receptor
CHEMBL203
EC50 8.7 6.7795 2.0 21
A-431
CHEMBL614069
IC50 8.69 6.1206 2.0 33
Receptor tyrosine-protein kinase erbB-3
CHEMBL5838
IC50 8.68 8.68 2.1 1
MGH121
CHEMBL6066770
IC50 8.59 6.865 2.6 2
BaF3
CHEMBL614524
EC50 8.49 7.3033 3.2 6
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
IC50 8.32 8.32 4.8 1
Epidermal growth factor receptor
CHEMBL3608
IC50 8.05 7.57 9.0 2
Cysteine--tRNA ligase, cytoplasmic
CHEMBL4105937
Kd 7.92 7.92 12.0 1
Lymphoma cell line
CHEMBL614114
IC50 7.82 7.82 15.0 2
BC
CHEMBL613535
IC50 7.82 7.82 15.0 2
Unchecked
CHEMBL612545
EC50 7.82 7.26 15.0 2
NCI-H1975
CHEMBL614348
EC50 7.72 7.72 19.0 1
Molecular identity unknown
CHEMBL612546
IC50 7.56 7.56 27.6 1
Non-small cell lung cancer cell line
CHEMBL615002
IC50 7.39 7.39 41.0 1
Activated CDC42 kinase 1
CHEMBL4599
IC50 7.15 7.15 71.0 1
CL97
CHEMBL4513122
IC50 7.0 7.0 100.0 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
EC50 6.91 6.91 122.0 1
Epidermal growth factor receptor
CHEMBL203
Kd 6.81 6.81 155.0 1
ALK tyrosine kinase receptor
CHEMBL4247
IC50 6.75 6.75 177.0 1
L02
CHEMBL4296457
IC50 6.52 5.76 300.0 5
Tyrosine-protein kinase Tec
CHEMBL4246
Kd 6.49 6.49 321.0 1
NCI-H460
CHEMBL396
IC50 6.38 6.38 415.9 1
LoVo
CHEMBL614721
IC50 6.32 6.32 480.0 1
Tyrosine-protein kinase BTK
CHEMBL5251
Kd 6.28 6.28 525.0 1
KG-1
CHEMBL612264
IC50 6.28 6.28 530.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 6.24 5.2733 570.0 3
HT-29
CHEMBL384
IC50 6.19 6.19 650.0 1
A-431
CHEMBL614069
EC50 6.17 6.1075 670.0 4
Calu-3
CHEMBL614534
IC50 6.12 6.12 750.0 1
Insulin receptor
CHEMBL1981
IC50 6.04 6.04 912.0 1
HeLa
CHEMBL399
IC50 6.01 5.875 975.0 2
MCF7
CHEMBL387
IC50 5.94 5.6067 1160.0 3
EA.hy 926
CHEMBL4296410
IC50 5.93 5.93 1161.0 1
MDA-MB-468
CHEMBL614335
IC50 5.89 5.89 1300.0 1
HepG2
CHEMBL395
IC50 5.79 5.65 1605.0 2
EML4-ALK
CHEMBL3883330
EC50 5.76 5.76 1748.0 1
A549
CHEMBL392
EC50 5.74 5.74 1830.0 1
HK-2
CHEMBL4296428
IC50 5.67 5.5775 2138.0 4
MDA-MB-231
CHEMBL400
IC50 5.65 5.65 2250.0 1
HUVEC
CHEMBL613979
IC50 5.62 5.46 2399.0 3

Pharmacokinetic Data

Parameter Value Units Species
AUC 699.47 ng.hr.mL-1 Mus musculus
AUC 937.3 ng.hr.mL-1 Rattus norvegicus
AUC 954.3 ng.hr.mL-1 Rattus norvegicus
AUC 141.0 ng.hr.mL-1 Rattus norvegicus
AUC 152.7 ng.hr.mL-1 Rattus norvegicus
AUC 883.0 ng.hr.mL-1 Rattus norvegicus
AUC 929.0 ng.hr.mL-1 Rattus norvegicus
AUC 796.0 ng.hr.mL-1 Rattus norvegicus
AUC 974.0 ng.hr.mL-1 Rattus norvegicus
AUC 33.62 ng.hr.mL-1 Rattus norvegicus
AUC 764.42 ng.hr.mL-1 Rattus norvegicus
AUC 691.0 ng.hr.mL-1 Mus musculus
AUC 1538.0 ng.hr.mL-1 Rattus norvegicus
CL 0.045 mL.min-1.kg-1 Rattus norvegicus
CL 14.2 L/hr Homo sapiens
CL 51.0 mL.min-1.g-1 Mus musculus
CL 4.1 mL.min-1.g-1 Homo sapiens
CL 228.4 mL.min-1.kg-1 Mus musculus
CL 40.0 mL.min-1.kg-1 Rattus norvegicus
CL 95.0 mL.min-1.kg-1 Canis lupus familiaris
CL 29.7 mL.min-1.kg-1 Macaca mulatta
CL 110.0 mL.min-1.kg-1 Rattus norvegicus
CL 62100.0 mL.min-1.g-1 Mus musculus
CL 37600.0 mL.min-1.g-1 Rattus norvegicus
CL 53200.0 mL.min-1.g-1 Canis lupus familiaris
CL 41700.0 mL.min-1.g-1 Macaca fascicularis
CL 8100.0 mL.min-1.g-1 Homo sapiens
CL 21.4 mL.min-1.kg-1 Homo sapiens
Cmax 380.0 nM Mus musculus
Cmax 222.17 nM Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
PC-9 IC50 = 0.011 nM 10.96 Antiproliferative activity against human PC-9 cells harboring EGFR L858R mutant ... 33429247
NCI-H1975 IC50 = 0.011 nM 10.96 Antiproliferative activity against human NCI-H1975 cells harboring EGFR T790M/L8... 33429247
NCI-H1975 IC50 = 0.019 nM 10.72 Antiproliferative activity against human NCI-H1975 cells expressing EGFR T790M/ ... 37087886
Epidermal growth factor receptor IC50 = 0.02 nM 10.7 Inhibition of human N-terminal GST-tagged EGFR L858R/T790M mutant (669 to 1210 r... 32931277
PC-9 IC50 = 0.023 nM 10.64 Antiproliferative activity against human PC-9 cells expressing EGFR Del19 mutant... 37087886
Epidermal growth factor receptor IC50 = 0.05 nM 10.3 Inhibition of EGFR L858R mutant (unknown origin) using TK-substrate preincubated... 37197473
Epidermal growth factor receptor IC50 = 0.058 nM 10.24 Inhibition of EGFR d746-750/T790M double mutant (unknown origin) 36064123
Epidermal growth factor receptor IC50 = 0.06 nM 10.22 Inhibition of human N-terminal GST-tagged EGFR L858R mutant (669 to 1210 residue... 32931277
Epidermal growth factor receptor IC50 = 0.16 nM 9.8 Inhibition of EGFR L858R/T790M (unknown origin) preincubated for 10 mins followe... 38169271
Epidermal growth factor receptor IC50 = 0.2 nM 9.7 Inhibition of human N-terminal GST-tagged EGFR (669 to 1210 residues) expressed ... 32931277
Epidermal growth factor receptor IC50 = 0.2 nM 9.7 Inhibition of recombinant human N-terminal GST tagged EGFR d746-750 mutant (669 ... 29523467
Epidermal growth factor receptor IC50 = 0.25 nM 9.6 Inhibition of EGFR L858R/T790M double mutant (unknown origin) 36064123
Epidermal growth factor receptor IC50 = 0.34 nM 9.47 Inhibition of EGFR T790M/L858R mutant (unknown origin) 38908104
Unchecked IC50 = 0.35 nM 9.46 Inhibition of human EGFR L858R/T790M double mutant expressed in Sf9 insect cells... 34668706
Epidermal growth factor receptor IC50 = 0.37 nM 9.43 Inhibition of EGFR L858R/T790M mutant (unknown origin) 38879996
Epidermal growth factor receptor IC50 = 0.421 nM 9.38 Inhibition of GST-tagged human EGFR A763_Y764insFHEA mutant using poly(Glu, Tyr)... 31560541
Epidermal growth factor receptor IC50 = 0.414 nM 9.38 Inhibition of EGFR T790M/C797S double mutant (unknown origin) using flurogenic s... 34794818
Epidermal growth factor receptor IC50 = 0.43 nM 9.37 Inhibition of EGFR L858R/T790M (unknown origin) by mobility shift assay 33493830
Epidermal growth factor receptor IC50 = 0.5 nM 9.3 Inhibition of recombinant human N-terminal GST tagged EGFR L858R mutant (669 to ... 29523467
Epidermal growth factor receptor IC50 = 0.5 nM 9.3 Inhibition of EGFR (unknown origin) Del19 mutant preincubated with compound 30 m... 36384036

Literature References

PubMed DOI Target Context # Activities
33459024 10.1021/acs.jmedchem.0c02005 ADMET 25
28282122 10.1021/acs.jmedchem.6b01907 Epidermal growth factor receptor 23
28287083 10.1038/ncomms14768 Unchecked 22
37042119 10.1021/acs.jmedchem.3c00027 NCI-H1975 17
28528303 10.1016/j.ejmech.2017.04.079 Epidermal growth factor receptor 16
37042119 10.1021/acs.jmedchem.3c00027 A549 16
37042119 10.1021/acs.jmedchem.3c00027 HCC827 16
37042119 10.1021/acs.jmedchem.3c00027 A-431 16
31951960 10.1016/j.ejmech.2020.112061 HCC827 15
28225269 10.1021/acs.jmedchem.6b01626 Epidermal growth factor receptor 15
33667898 10.1016/j.bmc.2021.116094 ADMET 14
38134304 10.1021/acs.jmedchem.3c01502 Epidermal growth factor receptor 14
28603991 10.1021/acs.jmedchem.7b00316 Epidermal growth factor receptor 13
28287083 10.1038/ncomms14768 Epidermal growth factor receptor 12
37042119 10.1021/acs.jmedchem.3c00027 Epidermal growth factor receptor 12
36384036 10.1021/acs.jmedchem.2c01041 BaF3 12
28426996 10.1016/j.ejmech.2017.04.036 Rattus norvegicus 12
39094277 10.1016/j.ejmech.2024.116711 Unchecked 12
39094277 10.1016/j.ejmech.2024.116711 PC-9 12
37870244 10.1021/acs.jmedchem.3c01400 Unchecked 11

Data from ChEMBL 36 via Core Engine