Compound Detail

CHEMBL1983268

ENTRECTINIB

💊 Approved Drug

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💊 Approved Drug

CN1CCN(c2ccc(C(=O)Nc3n[nH]c4ccc(Cc5cc(F)cc(F)c5)cc34)c(NC3CCOCC3)c2)CC1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1983268
Name	ENTRECTINIB
Phase	Approved
Structure Type	MOL
InChI Key	HAYYBYPASCDWEQ-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

Entrectinib NMS-E628 Rozlytrek Rxdx-101

Targets

194

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

560.6

MW (Da)

5.03

ALogP

HBA

HBD

85.5

PSA (Å²)

0.29

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2019
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

USAN Stem	-tinib
USAN Year	2015

Extended Properties

Molecular Formula	C31H34F2N6O2
MW	560.65
Aromatic Rings	4
Heavy Atoms	41
NP-Likeness	-1.35

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Neurotrophic tyrosine kinase receptor inhibitor	INHIBITOR	Neurotrophic tyrosine kinase receptor	✓	✓
Proto-oncogene tyrosine-protein kinase ROS inhibitor	INHIBITOR	Proto-oncogene tyrosine-protein kinase ROS	✓	✓
ALK tyrosine kinase receptor inhibitor	INHIBITOR	ALK tyrosine kinase receptor	✓	✓

Indications

Carcinoma, Non-Small-Cell Lung Neoplasms Neoplasms Carcinoma, Lobular Hematologic Neoplasms Melanoma Thyroid Neoplasms Glioma Leukemia, Myeloid, Acute Uveal Melanoma

ATC Classification

L01EX14

entrectinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 133 meas. best 9.7

Ki 56 meas. best 9.0

Kd 4 meas. best 8.7

EC50 1 meas. best 5.61

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Proto-oncogene tyrosine-protein kinase ROS CHEMBL5568	IC50	9.7	8.2622	0.2	9
High affinity nerve growth factor receptor CHEMBL2815	IC50	9.66	8.6363	0.2	19
ALK tyrosine kinase receptor CHEMBL4247	Ki	9.0	8.605	1.0	2
BDNF/NT-3 growth factors receptor CHEMBL4898	IC50	9.0	8.5767	1.0	9
NT-3 growth factor receptor CHEMBL5608	IC50	9.0	8.451	1.0	10
ALK tyrosine kinase receptor CHEMBL4247	IC50	8.8	7.5092	1.6	37
High affinity nerve growth factor receptor CHEMBL2815	Ki	8.8	8.8	1.6	1
NT-3 growth factor receptor CHEMBL5608	Ki	8.8	8.8	1.6	1
Leukocyte tyrosine kinase receptor CHEMBL5627	Ki	8.8	8.8	1.6	1
KM12 CHEMBL614709	IC50	8.77	7.85	1.7	7
High affinity nerve growth factor receptor CHEMBL2815	Kd	8.7	8.7	2.0	1
BDNF/NT-3 growth factors receptor CHEMBL4898	Ki	8.6	8.6	2.5	1
Tyrosine-protein kinase Fer CHEMBL3982	Ki	8.3	8.3	5.0	1
Tyrosine-protein kinase FRK CHEMBL4223	Ki	7.8	7.8	15.8	1
Tyrosine-protein kinase JAK2 CHEMBL2971	Ki	7.7	7.7	19.9	1
SU-DHL-1 CHEMBL2366200	IC50	7.7	7.7	20.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	7.62	7.34	24.0	5
EML4-ALK CHEMBL3883330	IC50	7.55	6.9233	28.0	3
KARPAS-299 CHEMBL2366156	IC50	7.51	7.315	31.0	2
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	Ki	7.5	7.5	31.6	1
Activated CDC42 kinase 1 CHEMBL4599	Ki	7.5	7.5	31.6	1
Serine/threonine-protein kinase PLK4 CHEMBL3788	Ki	7.4	7.4	39.8	1
Macrophage colony-stimulating factor 1 receptor CHEMBL1844	Ki	7.4	7.4	39.8	1
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	7.4	7.4	40.0	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Ki	7.4	7.4	39.8	1
Tyrosine-protein kinase receptor UFO CHEMBL4895	Ki	7.4	7.4	39.8	1
Unchecked CHEMBL612545	IC50	7.39	7.02	41.0	3
Insulin-like growth factor 1 receptor CHEMBL1957	Ki	7.2	7.2	63.1	1
NCI-H2228 CHEMBL1075536	IC50	7.17	6.9767	68.0	3
Activated CDC42 kinase 1 CHEMBL4599	IC50	7.16	7.16	70.0	1
MV4-11 CHEMBL613835	IC50	7.09	7.09	81.0	1
Focal adhesion kinase 1 CHEMBL2695	Ki	7.0	7.0	100.0	1
Tyrosine-protein kinase JAK1 CHEMBL2835	IC50	6.95	6.95	112.0	1
Insulin-like growth factor 1 receptor CHEMBL1957	IC50	6.91	6.6625	122.0	4
Focal adhesion kinase 1 CHEMBL2695	IC50	6.85	6.85	140.0	1
STE20-like serine/threonine-protein kinase CHEMBL4202	Ki	6.8	6.8	158.5	1
Tyrosine-protein kinase BTK CHEMBL5251	Ki	6.8	6.8	158.5	1
Mast/stem cell growth factor receptor Kit CHEMBL1936	Ki	6.8	6.8	158.5	1
Fibroblast growth factor receptor 3 CHEMBL2742	Ki	6.8	6.8	158.5	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	6.79	6.79	164.0	1
Protein-tyrosine kinase 6 CHEMBL4601	IC50	6.71	6.71	195.0	1
Dual specificity protein kinase CLK4 CHEMBL4203	Ki	6.7	6.7	199.5	1
Vascular endothelial growth factor receptor 3 CHEMBL1955	Ki	6.7	6.7	199.5	1
Tyrosine-protein kinase Lyn CHEMBL3905	Ki	6.7	6.7	199.5	1
Tyrosine-protein kinase Blk CHEMBL2250	Ki	6.7	6.7	199.5	1
Insulin receptor CHEMBL1981	IC50	6.68	6.68	209.0	1
Aurora kinase A CHEMBL4722	IC50	6.67	6.52	215.0	4
Macrophage-stimulating protein receptor CHEMBL2689	Ki	6.6	6.6	251.2	1
Aurora kinase A CHEMBL4722	Ki	6.6	6.6	251.2	1
Fibroblast growth factor receptor 1 CHEMBL3650	Ki	6.6	6.6	251.2	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	10988.74	ng.hr.mL-1	Mus musculus
AUC	9755.31	ng.hr.mL-1	Mus musculus
AUC	8465.81	ng.hr.mL-1	Rattus norvegicus
AUC	2876.13	ng.hr.mL-1	Rattus norvegicus
AUC	9867.44	ng.hr.mL-1	Canis lupus familiaris
AUC	3195.7	ng.hr.mL-1	Canis lupus familiaris
CL	33.0	mL.min-1.kg-1	Homo sapiens
CL	87.0	mL.min-1.kg-1	Rattus norvegicus
CL	13.5	mL.min-1.kg-1	Mus musculus
CL	20.8	mL.min-1.kg-1	Rattus norvegicus
CL	17.5	mL.min-1.kg-1	Canis lupus familiaris
Cmax	4900.0	nM	Mus musculus
Cmax	1330.0	nM	Mus musculus
Cmax	11000.0	nM	Rattus norvegicus
Cmax	500.0	nM	Rattus norvegicus
Cmax	8600.0	nM	Canis lupus familiaris
Cmax	600.0	nM	Canis lupus familiaris
F	77.0	%	Mus musculus
F	43.0	%	Rattus norvegicus
F	32.0	%	Canis lupus familiaris
T1/2	3.59	hr	Mus musculus
T1/2	2.94	hr	Mus musculus
T1/2	3.5	hr	Rattus norvegicus
T1/2	3.8	hr	Rattus norvegicus
T1/2	11.9	hr	Canis lupus familiaris
T1/2	15.2	hr	Canis lupus familiaris
Tmax	2.5	hr	Mus musculus
Tmax	3.08	hr	Rattus norvegicus
Tmax	2.0	hr	Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Proto-oncogene tyrosine-protein kinase ROS	IC50	=	0.2	nM	9.7	Inhibition of ROS1 (unknown origin)	35033885
High affinity nerve growth factor receptor	IC50	=	0.22	nM	9.66	Inhibition of human wild type TrkA kinase domain expressed in mouse NIH/3T3 cell...	31444087
High affinity nerve growth factor receptor	IC50	=	0.6	nM	9.22	Enzyme Assay: In each well of a 384-well plate, 1 nM-1.5 nM of wild type NTRK1 e...	-
High affinity nerve growth factor receptor	IC50	=	0.6	nM	9.22	NTRK1 Wild Type Assay at 1 mM ATP: In each well of a 384-well plate, 1 nM-1.5 nM...	-
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of wild type TRAK (unknown origin) incubated for 30 mins by caliper m...	33069129
ALK tyrosine kinase receptor	Ki	=	1.0	nM	9.0	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na...	-
NT-3 growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TRKC (unknown origin)	37413881
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TRKA (unknown origin)	38852338
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TRKA (unknown origin) by TR-FRET assay	36095945
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TRKA (unknown origin) by radiometric assay	35007864
BDNF/NT-3 growth factors receptor	IC50	=	1.0	nM	9.0	Inhibition of TrkB (unknown origin)	35033885
NT-3 growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TrkC (unknown origin)	35033885
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TrkA (unknown origin)	35033885
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TrkA (unknown origin) by radiometric assay	34253025
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TRKA (unknown origin) by radiometric assay	34628036
High affinity nerve growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of TRKA (unknown origin) in presence of gamma33-ATP	27003761
High affinity nerve growth factor receptor	Ki	=	1.585	nM	8.8	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na...	-
Leukocyte tyrosine kinase receptor	Ki	=	1.585	nM	8.8	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na...	-
NT-3 growth factor receptor	Ki	=	1.585	nM	8.8	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na...	-
ALK tyrosine kinase receptor	IC50	=	1.6	nM	8.8	Inhibition of ALK (unknown origin)	35033885

Literature References

PubMed	DOI	Target Context	# Activities
27003761	10.1021/acs.jmedchem.6b00064	Unchecked	52
27003761	10.1021/acs.jmedchem.6b00064	Mus musculus	19
27003761	10.1021/acs.jmedchem.6b00064	Canis familiaris	10
27003761	10.1021/acs.jmedchem.6b00064	Rattus norvegicus	10
-	10.6019/CHEMBL5303304	U2OS	9
-	10.6019/CHEMBL5303304	HEK-293T	8
27003761	10.1021/acs.jmedchem.6b00064	NON-PROTEIN TARGET	7
-	10.6019/CHEMBL5303304	Fibroblast	7
27003761	10.1021/acs.jmedchem.6b00064	Tropomyosin alpha-3 chain/High affinity nerve growth factor receptor	5
37030091	10.1016/j.ejmech.2023.115291	High affinity nerve growth factor receptor	4
27003761	10.1021/acs.jmedchem.6b00064	ADMET	4
27003761	10.1021/acs.jmedchem.6b00064	NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor)	4
29191878	10.1126/science.aan4368	Unchecked	4
31444087	10.1016/j.bmcl.2019.126624	High affinity nerve growth factor receptor	3
27003761	10.1021/acs.jmedchem.6b00064	EML4-ALK	3
27003761	10.1021/acs.jmedchem.6b00064	Proto-oncogene tyrosine-protein kinase ROS	2
27003761	10.1021/acs.jmedchem.6b00064	High affinity nerve growth factor receptor	2
27003761	10.1021/acs.jmedchem.6b00064	BDNF/NT-3 growth factors receptor	2
-	10.6019/CHEMBL4495565	SARS-CoV-2	2
27003761	10.1021/acs.jmedchem.6b00064	ALK tyrosine kinase receptor	2

Data from ChEMBL 36 via Core Engine