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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4937 1256580-46-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • alectinib
  • alectinib hydrochloride
  • alecensa
  • CH5424802
  • alectinib HCl
  • RO5424802
  • RO-5424802
Alectinib is a tyrosine kinase inhibitor that targets ALK and RET. In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions, amplifications, or activating mutations. The major active metabolite of alectinib, M4, showed similar in vitro potency and activity.
  • Molecular weight: 482.63
  • Formula: C30H34N4O2
  • CLOGP: 5.53
  • LIPINSKI: 1
  • HAC: 6
  • HDO: 1
  • TPSA: 72.36
  • ALOGS: -4.66
  • ROTB: 3

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 6.35 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 7.69 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 11.70 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Feb. 16, 2017 EMA Roche Registration Limited
Dec. 11, 2015 FDA HOFFMAN-LA ROCHE
July 4, 2014 PMDA

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 131.24 33.43 47 1873 26636 46657506
Metastases to central nervous system 91.75 33.43 29 1891 11192 46672950
Constipation 64.90 33.43 55 1865 174042 46510100
Death 59.97 33.43 71 1849 335477 46348665
Blood creatine phosphokinase increased 41.42 33.43 21 1899 27703 46656439
Pleural effusion 38.82 33.43 30 1890 82922 46601220
Pneumonitis 35.23 33.43 19 1901 28401 46655741

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 69.22 36.56 27 1295 17996 29933160
Death 63.97 36.56 78 1244 357205 29593951
Pneumonitis 52.10 36.56 25 1297 27429 29923727
Metastases to central nervous system 46.93 36.56 16 1306 7268 29943888
Interstitial lung disease 43.24 36.56 29 1293 60168 29890988

Pharmacologic Action:

SourceCodeDescription
ATC L01ED03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
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
Anaplastic lymphoma kinase positive anaplastic large cell lymphoma indication 738770003

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.42 acidic
pKa2 7.47 Basic
pKa3 4.89 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 150MG BASE ALECENSA HOFFMANN-LA ROCHE N208434 Dec. 11, 2015 RX CAPSULE ORAL Dec. 11, 2022 TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB
EQ 150MG BASE ALECENSA HOFFMANN-LA ROCHE N208434 Dec. 11, 2015 RX CAPSULE ORAL Nov. 6, 2024 FOR TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK) POSITIVE, METASTATIC NON-SMALL-CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA APPROVED TEST, EXCLUDING PATIENTS WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase INHIBITOR IC50 8.32 SCIENTIFIC LITERATURE DRUG LABEL
ALK tyrosine kinase receptor Kinase INHIBITOR IC50 8.72 SCIENTIFIC LITERATURE DRUG LABEL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.85 CHEMBL

External reference:

IDSource
LIJ4CT1Z3Y UNII
D10450 KEGG_DRUG
1256589-74-8 SECONDARY_CAS_RN
4035251 VANDF
C4060047 UMLSCUI
CHEBI:62268 CHEBI
EMH PDB_CHEM_ID
CHEMBL1738797 ChEMBL_ID
CHEMBL3707320 ChEMBL_ID
DB11363 DRUGBANK_ID
49806720 PUBCHEM_CID
9699 INN_ID
C582670 MESH_SUPPLEMENTAL_RECORD_UI
7739 IUPHAR_LIGAND_ID
1727454 RXNORM
237548 MMSL
31372 MMSL
d08405 MMSL
016628 NDDF
016629 NDDF
716039000 SNOMEDCT_US
716040003 SNOMEDCT_US
781316007 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ALECENSA HUMAN PRESCRIPTION DRUG LABEL 1 50242-130 CAPSULE 150 mg ORAL NDA 28 sections