Compound Detail

CHEMBL3286830

LORLATINIB

💊 Approved Drug

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💊 Approved Drug

C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)c2ccc(F)cc21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3286830
Name	LORLATINIB
Phase	Approved
Structure Type	MOL
InChI Key	IIXWYSCJSQVBQM-LLVKDONJSA-N
Therapeutic	✓ Yes

Known Names

Lorbrena Lorlatinib Lorviqua PF-06463922

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

406.4

MW (Da)

2.80

ALogP

HBA

HBD

110.1

PSA (Å²)

0.61

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2018
Availability	Prescription
Chirality	Single Enantiomer

Routes of Administration

Oral

USAN Stem	-tinib
USAN Year	2015

Extended Properties

Molecular Formula	C21H19FN6O2
MW	406.42
Aromatic Rings	3
Heavy Atoms	30
NP-Likeness	-0.62

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
ALK tyrosine kinase receptor inhibitor	INHIBITOR	ALK tyrosine kinase receptor	✓	✓
EML4-ALK inhibitor	INHIBITOR	EML4-ALK	✓	✓

Indications

Carcinoma, Non-Small-Cell Lung Lymphoma Neoplasms Neoplasms Ganglioneuroblastoma Neuroblastoma Lung Neoplasms Lymphoma, Large-Cell, Anaplastic Kidney Diseases Liver Diseases

ATC Classification

L01ED05

lorlatinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 60 meas. best 9.72

Ki 24 meas. best 10.0

EC50 1 meas. best 8.24

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Proto-oncogene tyrosine-protein kinase ROS CHEMBL5568	Ki	10.0	9.3067	0.1	3
SLC34A2-ROS1 CHEMBL4680045	IC50	9.72	9.72	0.2	1
EML4-ALK CHEMBL3883330	IC50	9.7	8.153	0.2	10
ALK tyrosine kinase receptor CHEMBL4247	IC50	9.7	7.9436	0.2	28
CD74-ROS1 CHEMBL4680046	IC50	9.64	9.64	0.2	1
ALK tyrosine kinase receptor CHEMBL4247	Ki	9.15	8.9733	0.7	6
BaF3 CHEMBL614524	IC50	8.92	7.622	1.2	5
Leukocyte tyrosine kinase receptor CHEMBL5627	Ki	8.57	8.57	2.7	1
Leukocyte tyrosine kinase receptor CHEMBL5627	IC50	8.57	8.57	2.7	1
KARPAS-299 CHEMBL2366156	IC50	8.52	8.52	3.0	1
Tyrosine-protein kinase Fer CHEMBL3982	Ki	8.48	8.48	3.3	1
Tyrosine-protein kinase Fer CHEMBL3982	IC50	8.48	8.48	3.3	1
SU-DHL-1 CHEMBL2366200	IC50	8.31	8.31	4.9	1
Proto-oncogene tyrosine-protein kinase ROS CHEMBL5568	EC50	8.24	8.24	5.8	1
Tyrosine-protein kinase Fes/Fps CHEMBL5455	IC50	8.22	8.22	6.0	1
Tyrosine-protein kinase Fes/Fps CHEMBL5455	Ki	8.22	8.22	6.0	1
NCI-H3122 CHEMBL4296475	IC50	8.11	8.11	7.8	1
Protein-tyrosine kinase 2-beta CHEMBL5469	Ki	7.85	7.85	14.0	1
Protein-tyrosine kinase 2-beta CHEMBL5469	IC50	7.85	7.85	14.0	1
Focal adhesion kinase 1 CHEMBL2695	Ki	7.77	7.77	17.0	1
Focal adhesion kinase 1 CHEMBL2695	IC50	7.77	7.77	17.0	1
Activated CDC42 kinase 1 CHEMBL4599	IC50	7.77	7.77	17.0	1
Activated CDC42 kinase 1 CHEMBL4599	Ki	7.77	7.77	17.0	1
BDNF/NT-3 growth factors receptor CHEMBL4898	Ki	7.64	7.64	23.0	3
High affinity nerve growth factor receptor CHEMBL2815	IC50	7.62	7.62	24.0	1
High affinity nerve growth factor receptor CHEMBL2815	Ki	7.62	7.62	24.0	1
Activin receptor type-1 CHEMBL5903	IC50	7.54	7.54	29.0	1
NT-3 growth factor receptor CHEMBL5608	Ki	7.34	7.34	46.0	1
NT-3 growth factor receptor CHEMBL5608	IC50	7.34	7.34	46.0	1
Tyrosine-protein kinase FRK CHEMBL4223	IC50	7.28	7.28	53.0	1
Tyrosine-protein kinase FRK CHEMBL4223	Ki	7.28	7.28	53.0	1
Epidermal growth factor receptor CHEMBL203	Ki	7.25	6.875	56.0	2
Proto-oncogene tyrosine-protein kinase ROS CHEMBL5568	IC50	7.11	7.11	78.0	1
HCC78 CHEMBL4296421	IC50	6.45	6.45	357.0	1
Tyrosine-protein kinase JAK2 CHEMBL2971	Ki	6.28	6.28	529.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	1150.0	ng.hr.mL-1	Rattus norvegicus
AUC	14933.0	ng.hr.mL-1	Rattus norvegicus
AUC	1412.31	ng.hr.mL-1	Rattus norvegicus
AUC	7973.96	ng.hr.mL-1	Rattus norvegicus
AUC	12477.09	ng.hr.mL-1	Rattus norvegicus
CL	8.0	mL.min-1.kg-1	Homo sapiens
CL	15.5	mL.min-1.kg-1	Rattus norvegicus
CL	8.0	mL.min-1.kg-1	Homo sapiens
CL	8.0	mL.min-1.g-1	Homo sapiens
Cmax	4249.3	nM	Rattus norvegicus
F	100.0	%	Rattus norvegicus
F	100.0	%	Rattus norvegicus
F	81.0	%	Homo sapiens
Fu	0.36	-	Rattus norvegicus
Fu	0.12	-	Rattus norvegicus
T1/2	2.7	hr	Rattus norvegicus
T1/2	25.0	hr	Homo sapiens
Tmax	1.3	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Proto-oncogene tyrosine-protein kinase ROS	Ki	=	0.1	nM	10.0	Inhibition of ROS1 L2026M mutant (unknown origin)	28431340
Proto-oncogene tyrosine-protein kinase ROS	Ki	=	0.1	nM	10.0	Inhibition of ROS1 L2026M mutant (unknown origin) in presence of ATP by microflu...	32432477
SLC34A2-ROS1	IC50	=	0.19	nM	9.72	Inhibition of SLC34A2-ROS1 (unknown origin) expressed in human HCC78 cells asses...	30258534
EML4-ALK	IC50	=	0.2	nM	9.7	Inhibition of wild type EML4/ALK F1174L mutant (unknown origin) expressed in NIH...	28431340
ALK tyrosine kinase receptor	IC50	=	0.2	nM	9.7	Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cell...	24819116
CD74-ROS1	IC50	=	0.23	nM	9.64	Inhibition of CD74-ROS1 (unknown origin) expressed in mouse BaF3 cells assessed ...	30258534
ALK tyrosine kinase receptor	Ki	=	0.7	nM	9.15	Binding affinity to ALK L1196M mutant (unknown origin) assessed as inhibition co...	38389874
ALK tyrosine kinase receptor	Ki	=	0.7	nM	9.15	Inhibition of human recombinant ALK L1196M mutant kinase domain (amino acids 109...	24819116
ALK tyrosine kinase receptor	Ki	=	0.7	nM	9.15	Inhibition of ALK L1196M mutant (unknown origin)	30258534
ALK tyrosine kinase receptor	Ki	=	0.7	nM	9.15	Inhibition of ALK (unknown origin)	28431340
ALK tyrosine kinase receptor	Ki	=	0.7	nM	9.15	Inhibition of ALK L1196M mutant (unknown origin)	29589935
BaF3	IC50	=	1.2	nM	8.92	Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72...	29288940
EML4-ALK	IC50	=	1.3	nM	8.89	Inhibition of wild type EML4/ALK (unknown origin) expressed in NIH/3T3 cells	28431340
ALK tyrosine kinase receptor	IC50	=	1.3	nM	8.89	Affinity On-target Cellular interaction (ELISA (ALK phosphoryaltion in 3T3-EML4-...	-
ALK tyrosine kinase receptor	IC50	=	1.3	nM	8.89	Inhibition of wild type human EML4-fused ALK expressed in mouse NIH-3T3 cells as...	24819116
EML4-ALK	IC50	=	1.6	nM	8.8	Inhibition of wild type EML4/ALK C1156Y mutant (unknown origin) expressed in NIH...	28431340
ALK tyrosine kinase receptor	IC50	=	1.6	nM	8.8	Inhibition of human EML4-fused ALK C1156Y mutant expressed in mouse NIH-3T3 cell...	24819116
Leukocyte tyrosine kinase receptor	IC50	=	2.7	nM	8.57	Inhibition of LTK (unknown origin) by TR-FRET-based Z'-LYTE assay	24819116
Leukocyte tyrosine kinase receptor	Ki	=	2.7	nM	8.57	Selectivity interaction (Z’-LYTE assay (SelectScreen Invitrogen)) EUB0000690a LT...	-
BaF3	IC50	=	2.9	nM	8.54	Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 ...	29288940

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	HEK-293T	261
-	10.6019/CHEMBL4689842	Fibroblast	261
-	10.6019/CHEMBL4689842	U2OS	261
24819116	10.1021/jm500261q	Unchecked	12
24819116	10.1021/jm500261q	ALK tyrosine kinase receptor	11
28431340	10.1016/j.ejmech.2017.04.032	EML4-ALK	9
24819116	10.1021/jm500261q	Rattus norvegicus	9
29288940	10.1016/j.ejmech.2017.12.060	ALK tyrosine kinase receptor	8
29288940	10.1016/j.ejmech.2017.12.060	BaF3	6
28431340	10.1016/j.ejmech.2017.04.032	ADMET	6
37036171	10.1021/acs.jmedchem.2c01864	BaF3	6
24819116	10.1021/jm500261q	Plasma	5
-	10.6019/CHEMBL4808148	Histone deacetylase 6	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
28431340	10.1016/j.ejmech.2017.04.032	Proto-oncogene tyrosine-protein kinase ROS	3
30258534	10.1021/acsmedchemlett.8b00147	CD74-ROS1	2
30258534	10.1021/acsmedchemlett.8b00147	Proto-oncogene tyrosine-protein kinase ROS	2
30258534	10.1021/acsmedchemlett.8b00147	ALK tyrosine kinase receptor	2
-	10.6019/CHEMBL4651402	SARS-CoV-2	2
30258534	10.1021/acsmedchemlett.8b00147	SLC34A2-ROS1	2

Data from ChEMBL 36 via Core Engine