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:

DoseUnitRoute
1.20 g O

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 Chugai Pharmaceutical Co., Ltd

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 140.18 28.03 52 2335 29867 53316812
Metastases to central nervous system 95.32 28.03 31 2356 12026 53334653
Death 74.04 28.03 85 2302 357147 52989532
Constipation 71.94 28.03 64 2323 198348 53148331
Blood creatine phosphokinase increased 56.41 28.03 27 2360 28958 53317721
Pleural effusion 49.85 28.03 37 2350 88542 53258137
Pneumonitis 43.16 28.03 23 2364 30865 53315814
Disease progression 41.09 28.03 35 2352 101885 53244794
Interstitial lung disease 38.70 28.03 27 2360 58595 53288084
Drug resistance 31.11 28.03 16 2371 19946 53326733
Traumatic lung injury 30.21 28.03 8 2379 1515 53345164
Liver disorder 30.06 28.03 20 2367 40135 53306544
No adverse event 28.06 28.03 19 2368 39246 53307433

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
Death 73.18 37.01 89 1436 382428 32129573
Neoplasm progression 72.19 37.01 29 1496 19629 32492372
Pneumonitis 54.28 37.01 27 1498 30107 32481894
Metastases to central nervous system 52.80 37.01 18 1507 7690 32504311
Interstitial lung disease 44.20 37.01 31 1494 64970 32447031

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 ANAPLASTIC LYMPHOMA KINASE (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 ANAPLASTIC LYMPHOMA KINASE (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
ALK tyrosine kinase receptor Kinase INHIBITOR IC50 8.72 SCIENTIFIC LITERATURE DRUG LABEL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase INHIBITOR IC50 8.32 SCIENTIFIC LITERATURE DRUG LABEL
Tyrosine-protein kinase Fer Kinase Kd 5.42 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 4.53 CHEMBL
Dual specificity protein kinase CLK2 Kinase Kd 5.63 CHEMBL
Dual specificity protein kinase CLK3 Kinase Kd 5.86 CHEMBL
Cyclin-G-associated kinase Kinase Kd 6.59 CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 2 Kinase Kd 4.45 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.85 CHEMBL
SRSF protein kinase 1 Kinase IC50 6.71 CHEMBL
Ephrin type-A receptor 1 Kinase Kd 6.71 CHEMBL
Proto-oncogene tyrosine-protein kinase ROS Kinase Ki 5.70 CHEMBL
Peroxisomal acyl-coenzyme A oxidase 3 Enzyme Kd 5.58 CHEMBL
Peroxisomal acyl-coenzyme A oxidase 1 Enzyme Kd 6.57 CHEMBL
Casein kinase I isoform gamma-2 Kinase Kd 6.29 CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 5.77 CHEMBL

External reference:

IDSource
D10450 KEGG_DRUG
1256589-74-8 SECONDARY_CAS_RN
4035251 VANDF
CHEBI:90936 CHEBI
EMH PDB_CHEM_ID
CHEMBL1738797 ChEMBL_ID
C582670 MESH_SUPPLEMENTAL_RECORD_UI
7739 IUPHAR_LIGAND_ID
9699 INN_ID
DB11363 DRUGBANK_ID
LIJ4CT1Z3Y UNII
49806720 PUBCHEM_CID
1727454 RXNORM
237548 MMSL
31372 MMSL
d08405 MMSL
016628 NDDF
016629 NDDF
716039000 SNOMEDCT_US
716040003 SNOMEDCT_US
781316007 SNOMEDCT_US
C3853921 UMLSCUI
CHEMBL3707320 ChEMBL_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ALECENSA HUMAN PRESCRIPTION DRUG LABEL 1 50242-130 CAPSULE 150 mg ORAL NDA 29 sections