lorlatinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5302 1454846-35-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • lorlatinib
  • lorbrena
  • PF-06463922
  • PF-6463922
  • lorviqua
Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors.
  • Molecular weight: 406.42
  • Formula: C21H19FN6O2
  • CLOGP: 1.87
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 1
  • TPSA: 110.06
  • ALOGS: -3.57
  • ROTB: 0

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Sept. 21, 2018 PMDA Pfizer Japan Inc
Sept. 21, 2018 FDA PFIZER INC
June 6, 2019 EMA PFIZER EUROPE MA EEIG

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neoplasm progression 116.66 64.57 22 137 4646 2353280
Hypertriglyceridaemia 83.14 64.57 13 146 883 2357043
Hypercholesterolaemia 68.66 64.57 12 147 1606 2356320

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neoplasm progression 124.56 66.99 23 108 3244 1743406
Hypercholesterolaemia 75.32 66.99 13 118 1199 1745451

Pharmacologic Action:

SourceCodeDescription
ATC L01XE44 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175082 Kinase Inhibitors
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.76 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL 10420749 July 27, 2036 TREATMENT OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER, PROGRESSED ON: CRIZOTINIB + AT LEAST 1 OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB, OR CERITINIB AS FIRST ALK INHIBITOR FOR METASTATIC DISEASE.
25MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL 10420749 July 27, 2036 TREATMENT OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER, PROGRESSED ON: CRIZOTINIB + AT LEAST 1 OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB, OR CERITINIB AS FIRST ALK INHIBITOR FOR METASTATIC DISEASE.

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2023 NEW CHEMICAL ENTITY
25MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2023 NEW CHEMICAL ENTITY
100MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON ALECTINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
100MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
100MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DIESASE
25MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON ALECTINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
25MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
25MG LORBRENA PFIZER INC N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DIESASE

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
ALK tyrosine kinase receptor Kinase INHIBITOR Ki 9.96 SCIENTIFIC LITERATURE DRUG LABEL
Proto-oncogene tyrosine-protein kinase ROS Kinase INHIBITOR IC50 9.30 SCIENTIFIC LITERATURE DRUG LABEL
Leukocyte tyrosine kinase receptor Kinase INHIBITOR IC50 8.57 SCIENTIFIC LITERATURE DRUG LABEL
Tyrosine-protein kinase Fer Kinase INHIBITOR IC50 8.48 SCIENTIFIC LITERATURE DRUG LABEL
Tyrosine-protein kinase Fes/Fps Kinase INHIBITOR IC50 8.22 SCIENTIFIC LITERATURE DRUG LABEL
High affinity nerve growth factor receptor Kinase INHIBITOR IC50 7.62 SCIENTIFIC LITERATURE DRUG LABEL
BDNF/NT-3 growth factors receptor Kinase INHIBITOR IC50 7.64 SCIENTIFIC LITERATURE DRUG LABEL
NT-3 growth factor receptor Kinase INHIBITOR IC50 7.34 SCIENTIFIC LITERATURE DRUG LABEL
Focal adhesion kinase 1 Kinase INHIBITOR IC50 7.77 SCIENTIFIC LITERATURE DRUG LABEL
Protein-tyrosine kinase 2-beta Kinase INHIBITOR IC50 7.85 SCIENTIFIC LITERATURE DRUG LABEL
Activated CDC42 kinase 1 Kinase INHIBITOR IC50 7.77 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
2103164 RXNORM
017834 NDDF
35471 MMSL
d09047 MMSL
4037975 VANDF
782976007 SNOMEDCT_US
782995000 SNOMEDCT_US
71731823 PUBCHEM_CID
CHEBI:143117 CHEBI
OSP71S83EU UNII
10278 INN_ID
DB12130 DRUGBANK_ID
D11012 KEGG_DRUG
CHEMBL3286830 ChEMBL_ID
7476 IUPHAR_LIGAND_ID
C000590786 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Lorbrena HUMAN PRESCRIPTION DRUG LABEL 1 0069-0227 TABLET, FILM COATED 25 mg ORAL NDA 17 sections
Lorbrena HUMAN PRESCRIPTION DRUG LABEL 1 0069-0231 TABLET, FILM COATED 100 mg ORAL NDA 17 sections