alectinib 🐶 Veterinary Use | 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: 5.66
  • 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 141.26 28.45 53 2390 29104 50573577
Metastases to central nervous system 95.03 28.45 31 2412 11251 50591430
Death 78.69 28.45 87 2356 325292 50277389
Constipation 71.39 28.45 64 2379 185644 50417037
Blood creatine phosphokinase increased 59.97 28.45 28 2415 26339 50576342
Disease progression 55.55 28.45 42 2401 95824 50506857
Pleural effusion 50.10 28.45 37 2406 81417 50521264
Pneumonitis 45.31 28.45 24 2419 29486 50573195
Interstitial lung disease 39.22 28.45 27 2416 53149 50549532
Drug resistance 33.61 28.45 17 2426 18972 50583709
Liver disorder 32.50 28.45 21 2422 37201 50565480
Traumatic lung injury 30.04 28.45 8 2435 1433 50601248
Hepatic function abnormal 29.92 28.45 19 2424 32662 50570019
No adverse event 29.45 28.45 19 2424 33559 50569122
Haemolysis 29.29 28.45 11 2432 6005 50596676

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 79.00 35.16 93 1475 341991 29230968
Neoplasm progression 73.69 35.16 30 1538 18582 29554377
Metastases to central nervous system 55.91 35.16 19 1549 7112 29565847
Pneumonitis 55.91 35.16 28 1540 28016 29544943
Interstitial lung disease 53.68 35.16 35 1533 57683 29515276

FDA Adverse Event Reporting System (Geriatric)

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 132.35 30.39 56 3135 40908 64454633
Metastases to central nervous system 107.34 30.39 36 3155 13876 64481665
Interstitial lung disease 91.38 30.39 58 3133 97674 64397867
Death 87.78 30.39 113 3078 482592 64012949
Pneumonitis 76.55 30.39 41 3150 50324 64445217
Blood creatine phosphokinase increased 73.44 30.39 42 3149 58516 64437025
Constipation 67.43 30.39 69 3122 229268 64266273
Disease progression 61.56 30.39 53 3138 141627 64353914
Pleural effusion 54.26 30.39 47 3144 126512 64369029
Pericardial effusion 46.11 30.39 27 3164 39227 64456314
Haemolysis 45.51 30.39 18 3173 11021 64484520
Blood bilirubin increased 38.95 30.39 28 3163 57525 64438016
Liver disorder 38.52 30.39 27 3164 53324 64442217
Traumatic lung injury 34.99 30.39 10 3181 2266 64493275
Hepatic function abnormal 34.01 30.39 27 3164 64286 64431255
Bradycardia 33.60 30.39 35 3156 118184 64377357
Blood creatinine increased 32.99 30.39 37 3154 135745 64359796
Hyperbilirubinaemia 31.44 30.39 17 3174 21188 64474353

FDA Adverse Event Reporting System (Pediatric)

None

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 antineoplastic agents
CHEBI has role CHEBI:62434 ALK inhibitor

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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

Pharmaceutical products:

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