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
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

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
Metastases to central nervous system 154.08 28.68 47 3178 13058 63472739
Neoplasm progression 147.63 28.68 59 3166 36369 63449428
Disease progression 146.90 28.68 86 3139 122672 63363125
Death 92.86 28.68 104 3121 374277 63111520
Constipation 76.28 28.68 74 3151 224869 63260928
Haemolysis 69.91 28.68 22 3203 6746 63479051
Blood creatine phosphokinase increased 63.63 28.68 31 3194 30399 63455398
Pleural effusion 59.06 28.68 44 3181 93166 63392631
Drug resistance 49.86 28.68 24 3201 22909 63462888
Pneumonitis 45.47 28.68 26 3199 35196 63450601
Interstitial lung disease 40.92 28.68 30 3195 61878 63423919
Haemolytic anaemia 36.14 28.68 15 3210 10110 63475687
Liver disorder 35.44 28.68 26 3199 53661 63432136
Traumatic lung injury 33.52 28.68 9 3216 1580 63484217
Spur cell anaemia 32.93 28.68 5 3220 45 63485752
Oedema 32.74 28.68 32 3193 97590 63388207
No adverse event 31.81 28.68 22 3203 41383 63444414
Blood bilirubin increased 31.55 28.68 21 3204 37119 63448678
Hepatic function abnormal 31.55 28.68 21 3204 37121 63448676

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
Disease progression 116.04 33.55 75 2028 108002 34846826
Death 80.35 33.55 108 1995 397941 34556887
Metastases to central nervous system 73.76 33.55 25 2078 8180 34946648
Neoplasm progression 72.88 33.55 33 2070 23267 34931561
Interstitial lung disease 59.43 33.55 41 2062 65241 34889587
Pneumonitis 55.62 33.55 31 2072 33847 34920981
Haemolysis 54.89 33.55 20 2083 8074 34946754
Pericardial effusion 44.41 33.55 24 2079 24638 34930190

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
Disease progression 218.02 27.48 131 4184 184231 79555842
Metastases to central nervous system 156.87 27.48 51 4264 16324 79723749
Neoplasm progression 142.74 27.48 65 4250 51617 79688456
Interstitial lung disease 102.58 27.48 68 4247 112532 79627541
Death 98.58 27.48 136 4179 566378 79173695
Blood creatine phosphokinase increased 85.71 27.48 50 4265 66040 79674033
Pneumonitis 76.16 27.48 45 4270 60815 79679258
Pleural effusion 70.13 27.48 60 4255 145202 79594871
Constipation 64.75 27.48 78 4237 282972 79457101
Pericardial effusion 59.97 27.48 35 4280 46202 79693871
Drug resistance 57.52 27.48 33 4282 42180 79697893
Spur cell anaemia 56.05 27.48 9 4306 112 79739961
Hyperbilirubinaemia 49.80 27.48 25 4290 24493 79715580
Haemolysis 44.64 27.48 19 4296 12793 79727280
Hepatic function abnormal 41.06 27.48 33 4282 73074 79666999
Bradycardia 40.53 27.48 43 4272 135514 79604559
Blood bilirubin increased 39.56 27.48 31 4284 66201 79673872
Haemolytic anaemia 38.64 27.48 19 4296 17801 79722272
Traumatic lung injury 38.02 27.48 11 4304 2380 79737693
Liver disorder 37.12 27.48 31 4284 72386 79667687
Myalgia 34.19 27.48 46 4269 185595 79554478
Adenocarcinoma metastatic 32.20 27.48 6 4309 185 79739888
Metastases to bone 30.36 27.48 18 4297 24409 79715664
Aspartate aminotransferase increased 29.65 27.48 37 4278 138604 79601469
Rhabdomyolysis 29.55 27.48 32 4283 103099 79636974
Blood creatinine increased 29.42 27.48 39 4276 155018 79585055
Anaemia 29.03 27.48 70 4245 444945 79295128
Transaminases increased 28.28 27.48 23 4292 51720 79688353

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 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
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 5.77 CHEMBL
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
ATP-binding cassette sub-family G member 2 Transporter IC50 5.82 CHEMBL
Casein kinase I isoform gamma-2 Kinase Kd 6.29 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
Calcium/calmodulin-dependent protein kinase kinase 2 Kinase Kd 4.45 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.85 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
1256589-74-8 SECONDARY_CAS_RN
DB11363 DRUGBANK_ID
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
9699 INN_ID
49806720 PUBCHEM_CID
LIJ4CT1Z3Y UNII

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