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 261.14 33.03 68 914 26615 46658465
Hypercholesterolaemia 134.89 33.03 34 948 11496 46673584
Hypertriglyceridaemia 108.92 33.03 25 957 5679 46679401
Death 76.93 33.03 60 922 335488 46349592
Blood cholesterol increased 44.39 33.03 20 962 39993 46645087
Low density lipoprotein increased 38.33 33.03 11 971 5989 46679091
Hallucination, auditory 35.95 33.03 12 970 10744 46674336

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 295.09 48.85 68 511 17955 29933944
Hypercholesterolaemia 93.86 48.85 23 556 7569 29944330
Death 74.68 48.85 58 521 357225 29594674

Pharmacologic Action:

SourceCodeDescription
ATC L01ED05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:62434 alk inhibitor

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)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2023 NEW CHEMICAL ENTITY
25MG LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2023 NEW CHEMICAL ENTITY
100MG LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2024 EXPANDED INDICATION OF THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST
25MG LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2024 EXPANDED INDICATION OF THE TREATMENT OF ADULT PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA-APPROVED TEST
100MG LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (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 LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (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 LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (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 LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (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 LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (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 LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL Nov. 2, 2025 INDICATED FOR THE TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (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
100MG LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2028 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST, EXCLUDING PATIENTS WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB OR CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE
25MG LORBRENULL PFIZER N210868 Nov. 2, 2018 RX TABLET ORAL March 3, 2028 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST, EXCLUDING PATIENTS WHOSE DISEASE HAS PROGRESSED ON CRIZOTINIB AND AT LEAST ONE OTHER ALK INHIBITOR FOR METASTATIC DISEASE; OR ALECTINIB OR CERITINIB AS THE FIRST ALK INHIBITOR THERAPY FOR METASTATIC DISEASE

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
4037975 VANDF
C4735286 UMLSCUI
CHEBI:143117 CHEBI
53P PDB_CHEM_ID
5P8 PDB_CHEM_ID
QB4 PDB_CHEM_ID
CHEMBL3286830 ChEMBL_ID
D11012 KEGG_DRUG
DB12130 DRUGBANK_ID
C000590786 MESH_SUPPLEMENTAL_RECORD_UI
7476 IUPHAR_LIGAND_ID
10278 INN_ID
OSP71S83EU UNII
71731823 PUBCHEM_CID
2103164 RXNORM
296337 MMSL
35471 MMSL
d09047 MMSL
017834 NDDF
782976007 SNOMEDCT_US
782995000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Lorbrena HUMAN PRESCRIPTION DRUG LABEL 1 0069-0227 TABLET, FILM COATED 25 mg ORAL NDA 32 sections
Lorbrena HUMAN PRESCRIPTION DRUG LABEL 1 0069-0231 TABLET, FILM COATED 100 mg ORAL NDA 32 sections