LORLATINIB

/static/temp/default.svg Search structure
Trade Names
Synonyms
Status
Molecule Category UNKNOWN
ATC L01ED05
UNII OSP71S83EU

Structure

InChI Key IIXWYSCJSQVBQM-LLVKDONJSA-N
Smiles C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)c2ccc(F)cc21
InChI
InChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C21H19FN6O2
Molecular Weight 406.42
AlogP 2.8
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 0.0
Polar Surface Area 110.06
Molecular species NEUTRAL
Aromatic Rings 3.0
Heavy Atoms 30.0

Bioactivity

Mechanism of Action Action Reference
ALK tyrosine kinase receptor inhibitor INHIBITOR FDA
Protein: EML4-ALK
Description: Echinoderm microtubule-associated protein-like 4
Organism : Homo sapiens
Q9HC35 ENSG00000143924
Protein: ALK tyrosine kinase receptor
Description: ALK tyrosine kinase receptor
Organism : Homo sapiens
Q9UM73 ENSG00000171094
Protein: EML4-ALK
Description: ALK tyrosine kinase receptor
Organism : Homo sapiens
Q9UM73 ENSG00000171094
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Ack family
- 17 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Alk family
- 3 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Fak family
- 14 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Fer family
- 3 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Sev family
- 0 - 0-12 -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Src family
- 53 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Trk family
- 24 - 23-23 -
Enzyme Kinase Protein Kinase TKL protein kinase group TKL protein kinase STKR family TKL protein kinase STKR Type 1 subfamily
- 0-77 - 1-8 -
Surface antigen
- 0 - - -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC34 family of sodium phosphate co-transporters
- 0 - - -
Unclassified protein
- 0-77 - - -
Assay Description Organism Bioactivity Reference
Inhibition of wild type human recombinant ALK kinase domain (amino acids 1093 to 1141) expressed in baculovirus system using 5'FAM-KKSRGDYMTMQIG-CONH2 as substrate incubated for 15 mins prior to ATP addition measured after 1 hr by microfluidic mobility shift assay Homo sapiens 0.07 nM
Inhibition of human recombinant ALK L1196M mutant kinase domain (amino acids 1093 to 1141) expressed in baculovirus system using 5'FAM-KKSRGDYMTMQIG-CONH2 as substrate incubated for 15 mins prior to ATP addition measured after 1 hr by microfluidic mobility shift assay Homo sapiens 0.7 nM
Inhibition of wild type human EML4-fused ALK expressed in mouse NIH-3T3 cells assessed as phosphorylated ALK level after 1 hr by sandwich ELISA Homo sapiens 1.3 nM
Inhibition of human EML4-fused ALK L1196M mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 21.0 nM
Inhibition of TRKB (unknown origin) by off-chip mobility shift assay Homo sapiens 23.0 nM
Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 0.2 nM
Inhibition of human EML4-fused ALK C1156Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 1.6 nM
Inhibition of human EML4-fused ALK G1269A mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 15.0 nM
Inhibition of human EML4-fused ALK S1206Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 4.2 nM
Inhibition of human EML4-fused ALK L1152R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 9.0 nM
Inhibition of human EML4-fused ALK G1202R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 77.0 nM
Inhibition of human EML4-fused ALK 1151Tins mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA Homo sapiens 38.0 nM
Inhibition of ROS1 (unknown origin) by off-chip mobility shift assay Homo sapiens 0.02 nM
Inhibition of FER (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 3.3 nM
Inhibition of FES (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 6.0 nM
Inhibition of PTK2B (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 14.0 nM
Inhibition of TNK2 (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 17.0 nM
Inhibition of PTK2 (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 17.0 nM
Inhibition of NRTK1 (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 24.0 nM
Inhibition of NRTK3 (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 46.0 nM
Inhibition of FRK (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 53.0 nM
Inhibition of LTK (unknown origin) by TR-FRET-based Z'-LYTE assay Homo sapiens 2.7 nM
Inhibition of ALK L1196M mutant (unknown origin) Homo sapiens 0.7 nM
Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay Homo sapiens 7.8 nM
Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay Homo sapiens 4.9 nM
Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay Homo sapiens 3.0 nM
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay Mus musculus 2.9 nM
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay Mus musculus 42.4 nM
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay Mus musculus 200.0 nM
Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay Homo sapiens 357.0 nM
Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay Mus musculus 1.2 nM
Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay Mus musculus 262.0 nM
Inhibition of wild type ROS1 (unknown origin) Homo sapiens 0.025 nM
Inhibition of ROS1 L2026M mutant (unknown origin) Homo sapiens 0.1 nM
Inhibition of ROS1 G2032R mutant (unknown origin) Homo sapiens 12.0 nM
Inhibition of wild type EML4/ALK (unknown origin) expressed in NIH/3T3 cells Homo sapiens 1.3 nM
Inhibition of wild type EML4/ALK F1174L mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 0.2 nM
Inhibition of wild type EML4/ALK C1156Y mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 1.6 nM
Inhibition of wild type EML4/ALK G1269A mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 15.0 nM
Inhibition of wild type EML4/ALK S1206Y mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 4.2 nM
Inhibition of wild type EML4/ALK L1196M mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 21.0 nM
Inhibition of wild type EML4/ALK L1152R mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 9.0 nM
Inhibition of wild type EML4/ALK G1202R mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 77.0 nM
Inhibition of wild type EML4/ALK 1151Tins mutant (unknown origin) expressed in NIH/3T3 cells Homo sapiens 38.0 nM
Inhibition of ALK (unknown origin) Homo sapiens 0.7 nM
Inhibition of L1196M mutant (unknown origin) Homo sapiens 8.2 nM
Inhibition of TrkB (unknown origin) Homo sapiens 23.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 2.31 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 7.63 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -2.471 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.16 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.05 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.05 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.16 %
Inhibition of ROS1 L2026M mutant (unknown origin) in presence of ATP by microfluidic mobility shift assay Homo sapiens 0.1 nM
Inhibition of EML4/ALK L1196M mutant (unknown origin) Homo sapiens 21.0 nM
Inhibition of ALK L1196M mutant (unknown origin) Homo sapiens 0.7 nM
Inhibition of CD74-ROS1 (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell viability Homo sapiens 0.23 nM
Inhibition of ROS1 (unknown origin) Homo sapiens 0.025 nM
Inhibition of SLC34A2-ROS1 (unknown origin) expressed in human HCC78 cells assessed as reduction in cell viability Homo sapiens 0.19 nM

Cross References

Resources Reference
ChEBI 143117
ChEMBL CHEMBL3286830
DrugBank DB12130
DrugCentral 5302
FDA SRS OSP71S83EU
Guide to Pharmacology 7476
PDB 5P8
PubChem 71731823
SureChEMBL SCHEMBL15261807
ZINC ZINC000098208524
CONTENTS