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Compound Detail

CHEMBL1738797

ALECTINIB
💊 Approved Drug
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💊 Approved Drug
CCc1cc2c(cc1N1CCC(N3CCOCC3)CC1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O

Basic Information

ChEMBL ID CHEMBL1738797
Name ALECTINIB
Phase Approved
Structure Type MOL
InChI Key KDGFLJKFZUIJMX-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

AF-802 AF802 Alecensa Alectinib CH-5424802 CH5424802 RO-5424802 RO5424802
31
Targets
114
Activities
4
Assay Types
15
PK Parameters
20
Publications
8
Known Names
20
Indications

Molecular Properties

482.6
MW (Da)
4.77
ALogP
5
HBA
1
HBD
72.4
PSA (Ų)
0.58
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2015
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Natural Product Chemical Probe
USAN Stem -tinib
USAN Year 2013

Extended Properties

Molecular Formula C30H34N4O2
MW 482.63
Aromatic Rings 3
Heavy Atoms 36
NP-Likeness -0.21

Indications

Neoplasms Neoplasms Carcinoma, Non-Small-Cell Lung Brain Neoplasms Bronchial Neoplasms Cholangiocarcinoma Colorectal Neoplasms Digestive System Neoplasms Head and Neck Neoplasms Hematologic Neoplasms Intestinal Neoplasms Lung Neoplasms Lymphoma, Large-Cell, Anaplastic Melanoma Neuroendocrine Tumors Ovarian Neoplasms Pancreatic Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Salivary Gland Neoplasms

ATC Classification

L01ED03
alectinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 85 meas. best 9.23
EC50 13 meas. best 8.05
Kd 12 meas. best 6.71
Ki 4 meas. best 5.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
ALK tyrosine kinase receptor
CHEMBL4247
IC50 9.23 8.3733 0.6 15
Unchecked
CHEMBL612545
IC50 9.0 7.9967 1.0 3
EML4-ALK
CHEMBL3883330
IC50 8.7 7.38 2.0 27
KARPAS-299
CHEMBL2366156
IC50 8.52 8.2225 3.0 4
SR
CHEMBL614300
IC50 8.47 8.47 3.4 1
NB1
CHEMBL2366284
IC50 8.35 8.35 4.5 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
IC50 8.32 7.9031 4.8 16
NCI-H2228
CHEMBL1075536
IC50 8.19 7.735 6.5 2
NCI-H3122
CHEMBL4296475
IC50 8.05 7.7 9.0 2
NON-PROTEIN TARGET
CHEMBL3879801
EC50 8.05 6.3989 9.0 9
SRSF protein kinase 1
CHEMBL4375
IC50 7.96 7.335 11.0 2
NON-PROTEIN TARGET
CHEMBL3879801
IC50 7.82 7.5871 15.0 7
SRSF protein kinase 2
CHEMBL5668
IC50 7.55 7.55 28.2 1
Ephrin type-A receptor 1
CHEMBL5810
Kd 6.71 6.71 193.0 1
Cyclin-G-associated kinase
CHEMBL4355
Kd 6.59 6.59 259.0 1
Peroxisomal acyl-coenzyme A oxidase 1
CHEMBL4105748
Kd 6.57 6.57 271.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
Kd 6.43 6.43 369.0 1
Casein kinase I isoform gamma-2
CHEMBL2543
Kd 6.29 6.29 514.0 1
SK-N-SH
CHEMBL614924
EC50 6.06 6.06 872.0 1
SH-SY5Y
CHEMBL614910
EC50 5.94 5.94 1150.0 1
Dual specificity protein kinase CLK3
CHEMBL4226
Kd 5.86 5.86 1397.0 1
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 5.85 5.85 1400.0 2
Broad substrate specificity ATP-binding cassette transporter ABCG2
CHEMBL5393
IC50 5.82 5.82 1500.0 1
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform
CHEMBL2349
Kd 5.77 5.77 1711.0 1
Proto-oncogene tyrosine-protein kinase ROS
CHEMBL5568
Ki 5.7 5.66 2000.0 4
BaF3
CHEMBL614524
IC50 5.68 5.68 2067.0 1
SK-N-AS
CHEMBL1075578
EC50 5.67 5.67 2139.0 1
Dual specificity protein kinase CLK2
CHEMBL4225
Kd 5.63 5.63 2320.0 1
SK-N-FI
CHEMBL2366120
EC50 5.62 5.62 2401.0 1
Peroxisomal acyl-coenzyme A oxidase 3
CHEMBL4105817
Kd 5.58 5.58 2602.0 1
Tyrosine-protein kinase Fer
CHEMBL3982
Kd 5.42 5.42 3758.0 1
Dual specificity protein kinase CLK1
CHEMBL4224
Kd 4.53 4.53 29881.0 1
Calcium/calmodulin-dependent protein kinase kinase 2
CHEMBL5284
Kd 4.45 4.45 35559.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1400.0 ng.hr.mL-1 Rattus norvegicus
AUC 696.0 ng.hr.mL-1 Macaca fascicularis
CL 7.79 mL.min-1.kg-1 Rattus norvegicus
CL 6.04 mL.min-1.kg-1 Macaca fascicularis
CL 5.01 uL.min-1.(10^6cells)-1 Rattus norvegicus
Cmax 115.62 nM Macaca fascicularis
Cmax 125.98 nM Rattus norvegicus
F 50.4 % Macaca fascicularis
F 65.2 % Rattus norvegicus
Fu 0.003 - Homo sapiens
T1/2 10.4 hr Macaca fascicularis
T1/2 17.8 hr Rattus norvegicus
T1/2 8.38 hr Macaca fascicularis
T1/2 12.6 hr Rattus norvegicus
Vd 4016.0 l Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
ALK tyrosine kinase receptor IC50 = 0.59 nM 9.23 Inhibition of N-terminal GST tagged wild-type human ALK cytoplasmic domain (1058... 33185101
ALK tyrosine kinase receptor IC50 = 0.96 nM 9.02 Inhibition of human ALK S1206Y mutant expressed Sf9 cells pre-incubated for 30 m... 33185101
Unchecked IC50 = 1.0 nM 9.0 Inhibition of human ALK F1197M mutant expressed Sf9 cells pre-incubated for 30 m... 33185101
ALK tyrosine kinase receptor IC50 = 1.5 nM 8.82 Inhibition of human ALK L1196M mutant expressed Sf9 cells pre-incubated for 30 m... 33185101
ALK tyrosine kinase receptor IC50 = 1.56 nM 8.81 Inhibition of ALK L1196M (unknown origin) by TR-FRET assay 34402300
ALK tyrosine kinase receptor IC50 = 1.9 nM 8.72 Inhibition of ALK (unknown origin) by TR-FRET assay 34402300
ALK tyrosine kinase receptor IC50 = 1.9 nM 8.72 Inhibition of ALK (unknown origin) 31419130
ALK tyrosine kinase receptor IC50 = 1.9 nM 8.72 Inhibition of ALK (unknown origin) by TR-FRET assay 30565923
ALK tyrosine kinase receptor IC50 = 1.9 nM 8.72 Inhibition of ALK using Bio-Gastrintide as substrate by TR-FRET assay in presenc... 22225917
EML4-ALK IC50 = 2.0 nM 8.7 Inhibition of EML4-ALK S1206Y mutant (unknown origin) expressed in mouse Ba/F3 c... 26568289
EML4-ALK IC50 = 2.0 nM 8.7 Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 c... 26568289
EML4-ALK IC50 = 2.0 nM 8.7 Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells... 26568289
ALK tyrosine kinase receptor IC50 = 2.07 nM 8.68 Inhibition of ALK G1202R (unknown origin) 31419130
KARPAS-299 IC50 = 3.0 nM 8.52 Antiproliferative activity against human KARPAS-299 cells harbouring ALK by Cell... 34402300
KARPAS-299 IC50 = 3.0 nM 8.52 Antiproliferative activity against human KARPAS299 cells 31419130
KARPAS-299 IC50 = 3.0 nM 8.52 Antiproliferative activity against human KARPAS299 cells after 96 hrs by cell co... 22225917
EML4-ALK IC50 = 3.0 nM 8.52 Inhibition of EML4-ALK F1174L mutant (unknown origin) expressed in mouse Ba/F3 c... 26568289
SR IC50 = 3.4 nM 8.47 Antiproliferative activity against ALK positive human SR cells 33751979
ALK tyrosine kinase receptor IC50 = 3.9 nM 8.41 Inhibition of human ALK G1269A mutant expressed Sf9 cells pre-incubated for 30 m... 33185101
EML4-ALK IC50 = 4.5 nM 8.35 Inhibition of EML4/ALK in human NCI-H2228 cells 31419130

Literature References

PubMed DOI Target Context # Activities
27780853 10.1158/1078-0432.ccr-16-0569 EML4-ALK 42
27131066 10.1016/j.ejmech.2016.04.046 NON-PROTEIN TARGET 10
26568289 10.1021/acs.jmedchem.5b01136 NON-PROTEIN TARGET 9
26568289 10.1021/acs.jmedchem.5b01136 EML4-ALK 8
22225917 10.1016/j.bmc.2011.12.021 Rattus norvegicus 7
22225917 10.1016/j.bmc.2011.12.021 Cynomolgus monkey 7
38484122 10.1021/acs.jmedchem.3c02319 Proto-oncogene tyrosine-protein kinase receptor Ret 6
- 10.6019/CHEMBL5303304 U2OS 6
34402300 10.1021/acs.jmedchem.0c02167 Proto-oncogene tyrosine-protein kinase receptor Ret 6
25733882 10.1073/pnas.1420785112 Proto-oncogene tyrosine-protein kinase ROS 6
34176264 10.1021/acs.jmedchem.1c00270 ADMET 6
34176264 10.1021/acs.jmedchem.1c00270 KARPAS-299 5
- 10.6019/CHEMBL5303304 HEK-293T 5
33185101 10.1021/acs.jmedchem.0c01550 Unchecked 5
27780853 10.1158/1078-0432.ccr-16-0569 ADMET 5
34176264 10.1021/acs.jmedchem.1c00270 BaF3 5
37036171 10.1021/acs.jmedchem.2c01864 BaF3 5
- 10.6019/CHEMBL5303304 Fibroblast 4
27780853 10.1158/1078-0432.ccr-16-0569 BaF3 4
33185101 10.1021/acs.jmedchem.0c01550 ALK tyrosine kinase receptor 4

Data from ChEMBL 36 via Core Engine