alectinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.632 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 3.802 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 8.590 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 6.982 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.600 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 3.830 % High 1
herg hERG pIC50 5.064 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 3.126 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 29.717 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.560 % High 1
kinase-safety-class AAK1,ABL2,ACVR2A,ACVR2B,ACVRL1,AKT2,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK2,CDK3,CDK4,CDK5,CDK6,CDK7,CDK9,CHEK1,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,DYRK2,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB4,ERBB2,FGFR1,FLT3,FLT4,FYN,GAK,GRK1,GRK2,GSK3A,GSK3B,HASPIN,HIPK2,IGF1R,IKBKB,INSR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K19,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK12,MAPK7,MAPK8,MAPK9,MAPKAPK2,MARK1,MARK2,MARK4,MELK,MET,MINK1,MST1R,MTOR,NTRK1,NTRK2,NTRK3,NUAK1,PAK4,PDGFRB,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM1,PIM2,PIM3,PRKAA1,PRKAA2,PRKCD,PRKCZ,PRKDC,ROCK1,RPS6KA1,SGK1,SIK2,SIK3,SRC,STK10,STK17A,STK33,STK4,SYK,TEK,TGFBR1,TNIK,TTK,TYRO3,UHMK1,ULK1,ULK2,YES1,ZAP70 145
kinase-selectivity-class ABL2,ACVR2B,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2A,CAMK2B,CAMK2D,CDK1,CDK16,CDK2,CDK3,CDK4,CDK6,CDK7,CDK9,CHEK1,CLK2,CLK4,CSF1R,CSK,DDR1,DYRK1A,DYRK1B,DYRK3,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FGFR1,FLT3,FLT4,FYN,GAK,GSK3A,GSK3B,HIPK2,IGF1R,INSR,IRAK1,IRAK3,IRAK4,JAK1,JAK2,KDR,KIT,LCK,LRRK2,LYN,MAP3K10,MAP3K11,MAP3K14,MAP3K21,MAP3K7,MAP3K9,MAP4K1,MAP4K3,MAP4K5,MAPK1,MAPK7,MARK1,MARK3,MARK4,MELK,MET,MINK1,MST1R,NTRK1,NTRK3,NUAK1,PAK4,PDK1,PDK4,PIM3,PLK4,PRKAA1,PRKAA2,PRKCD,PRKCZ,PRKDC,PTK2,RET,SIK2,SIK3,SRC,STK10,STK33,STK4,SYK,TEK,TNIK,TNK1,TTK,TYRO3,ULK1,ULK2,YES1 103
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 5.260 High 1
mh-clint Mouse hepatocyte intrinsic clearance 16.255 High 1
mppb Mouse plasma protein binding (% unbound) 0.420 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 9.908 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.870 % High 1
rh-clint Rat hepatocyte intrinsic clearance 5.957 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 1.840 % High 1
rppb Rat plasma protein binding (% unbound) 0.670 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.558 uM High 1

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
No adverse event 282.21 26.24 119 5583 67863 90554882
Disease progression 264.53 26.24 148 5554 156467 90466278
Metastases to central nervous system 238.77 26.24 74 5628 17468 90605277
Blood bilirubin increased 183.22 26.24 77 5625 43393 90579352
Constipation 160.65 26.24 136 5566 280259 90342486
Neoplasm progression 148.92 26.24 67 5635 44419 90578326
Anaemia 135.71 26.24 137 5565 352665 90270080
Blood creatine phosphokinase increased 132.48 26.24 57 5645 33966 90588779
Death 97.44 26.24 131 5571 456420 90166325
Haemolytic anaemia 97.15 26.24 34 5668 11663 90611082
Aspartate aminotransferase increased 91.68 26.24 65 5637 102872 90519873
Drug resistance 68.70 26.24 35 5667 30414 90592331
Pleural effusion 67.34 26.24 56 5646 111935 90510810
Haemolysis 60.32 26.24 22 5680 8488 90614257
Hepatic function abnormal 60.07 26.24 37 5665 46251 90576494
Myalgia 59.86 26.24 64 5638 175061 90447684
Pneumonitis 59.09 26.24 36 5666 44134 90578611
Hyperbilirubinaemia 56.35 26.24 24 5678 13912 90608833
Oedema peripheral 53.29 26.24 73 5629 257842 90364903
Blood alkaline phosphatase increased 48.96 26.24 33 5669 48046 90574699
Alanine aminotransferase increased 47.18 26.24 47 5655 118291 90504454
Transaminases increased 46.40 26.24 29 5673 37163 90585582
Spur cell anaemia 44.91 26.24 7 5695 60 90622685
Pelvic haematoma 43.86 26.24 10 5692 722 90622023
Blood creatinine increased 43.65 26.24 42 5660 101344 90521401
Interstitial lung disease 41.38 26.24 36 5666 76369 90546376
Oedema 35.88 26.24 53 5649 200242 90422503
Retroperitoneal haematoma 32.67 26.24 11 5691 3357 90619388
Rhabdomyolysis 31.54 26.24 26 5676 51230 90571515
Retroperitoneal haemorrhage 29.64 26.24 10 5692 3070 90619675
Off label use 29.59 26.24 142 5560 1102110 89520635
Bradycardia 29.23 26.24 31 5671 83816 90538929
Anaplastic lymphoma kinase gene mutation 29.15 26.24 4 5698 12 90622733
Pericardial effusion 27.63 26.24 21 5681 36812 90585933
Erythema multiforme 27.38 26.24 14 5688 12232 90610513
Hypertriglyceridaemia 26.73 26.24 12 5690 7877 90614868

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 198.89 28.41 133 3489 143523 42474190
No adverse event 141.31 28.41 68 3554 38953 42578760
Metastases to central nervous system 121.47 28.41 42 3580 10313 42607400
Blood bilirubin increased 112.99 28.41 60 3562 42192 42575521
Neoplasm progression 71.35 28.41 39 3583 28961 42588752
Death 64.27 28.41 130 3492 471055 42146658
Pneumonitis 58.24 28.41 39 3583 41679 42576034
Blood creatine phosphokinase increased 57.63 28.41 41 3581 48297 42569416
Haemolysis 51.38 28.41 22 3600 9567 42608146
Interstitial lung disease 49.73 28.41 46 3576 78416 42539297
Blood creatinine increased 43.42 28.41 50 3572 109953 42507760
Myalgia 38.45 28.41 44 3578 96036 42521677
Pericardial effusion 37.58 28.41 26 3596 29249 42588464
Metastases to bone 36.62 28.41 20 3602 14789 42602924
Constipation 36.51 28.41 56 3566 162235 42455478
Hepatic function abnormal 36.11 28.41 32 3590 51535 42566178
Haemolytic anaemia 34.56 28.41 18 3604 12109 42605604
Metastases to salivary gland 33.74 28.41 6 3616 88 42617625
Aspartate aminotransferase increased 33.71 28.41 37 3585 77126 42540587
Osteosarcoma recurrent 32.04 28.41 6 3616 119 42617594
Anaemia 31.79 28.41 72 3550 280206 42337507
Drug resistance 31.74 28.41 25 3597 34223 42583490
Spur cell anaemia 29.13 28.41 5 3617 59 42617654
Bradycardia 29.00 28.41 36 3586 85448 42532265

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 352.20 24.41 220 7899 243814 110337366
No adverse event 279.88 24.41 127 7992 73712 110507468
Metastases to central nervous system 274.71 24.41 91 8028 22726 110558454
Blood bilirubin increased 273.29 24.41 126 7993 75846 110505334
Blood creatine phosphokinase increased 192.59 24.41 98 8021 72979 110508201
Anaemia 174.32 24.41 207 7912 546879 110034301
Constipation 167.53 24.41 166 7953 357620 110223560
Neoplasm progression 137.12 24.41 75 8044 64520 110516660
Aspartate aminotransferase increased 126.43 24.41 100 8019 159836 110421344
Death 93.22 24.41 176 7943 698693 109882487
Haemolytic anaemia 92.02 24.41 40 8079 20880 110560300
Interstitial lung disease 88.93 24.41 77 8042 139257 110441923
Drug resistance 86.43 24.41 53 8066 56321 110524859
Blood creatinine increased 85.60 24.41 85 8034 182804 110398376
Myalgia 83.75 24.41 92 8027 222289 110358891
Pneumonitis 78.54 24.41 56 8063 76475 110504705
Hyperbilirubinaemia 77.43 24.41 40 8079 30631 110550549
Hepatic function abnormal 77.36 24.41 59 8060 89236 110491944
Pleural effusion 74.79 24.41 78 8041 177631 110403549
Spur cell anaemia 73.30 24.41 12 8107 122 110581058
Alanine aminotransferase increased 65.67 24.41 74 8045 183699 110397481
Transaminases increased 59.60 24.41 44 8075 63346 110517834
Blood alkaline phosphatase increased 59.52 24.41 46 8073 70889 110510291
Oedema peripheral 58.26 24.41 94 8025 328566 110252614
Pericardial effusion 54.43 24.41 40 8079 57177 110524003
Bradycardia 49.46 24.41 59 8060 155458 110425722
Oedema 45.56 24.41 66 8053 209910 110371270
Pulmonary toxicity 41.51 24.41 22 8097 17724 110563456
Haemolysis 41.21 24.41 21 8098 15618 110565562
Pelvic haematoma 38.75 24.41 10 8109 1039 110580141
Metastases to bone 36.95 24.41 25 8094 31347 110549833
Hypertriglyceridaemia 34.91 24.41 19 8100 16135 110565045
Metastases to salivary gland 34.62 24.41 6 8113 88 110581092
Hyperuricaemia 33.95 24.41 18 8101 14513 110566667
Rhabdomyolysis 33.94 24.41 43 8076 120358 110460822
Sinus bradycardia 33.55 24.41 23 8096 29460 110551720
Osteosarcoma recurrent 31.58 24.41 6 8113 150 110581030
Traumatic lung injury 29.87 24.41 10 8109 2567 110578613
Photosensitivity reaction 29.20 24.41 20 8099 25569 110555611
Retroperitoneal haemorrhage 27.98 24.41 12 8107 6053 110575127
Erythema multiforme 27.72 24.41 18 8101 21079 110560101
Peritonitis 27.02 24.41 21 8098 32586 110548594
Adenocarcinoma metastatic 25.95 24.41 6 8113 394 110580786
Anaplastic lymphoma kinase gene mutation 25.54 24.41 5 8114 147 110581033
Non-small cell lung cancer 24.89 24.41 12 8107 7923 110573257

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
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:62434 EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor

Related Drugs by ATC class:

L01ED Anaplastic lymphoma kinase (ALK) inhibitors 4 drugs
brigatinibceritinibcrizotiniblorlatinib

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 April 18, 2027 FOR ADJUVANT TREATMENT IN ADULT PATIENTS FOLLOWING TUMOR RESECTION OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC) (TUMORS >/= 4 CM OR NODE POSITIVE), AS DETECTED BY AN FDA-APPROVED TEST
EQ 150MG BASE ALECENSA HOFFMANN-LA ROCHE N208434 Dec. 11, 2015 RX CAPSULE ORAL April 18, 2031 ADJUVANT TREATMENT IN ADULT PATIENTS FOLLOWING TUMOR RESECTION OF ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC) (TUMORS GREATER THAN OR EQUAL TO 4 CM OR NODE POSITIVE), AS DETECTED BY AN FDA-APPROVED TEST

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
Calcium/calmodulin-dependent protein kinase kinase 2 Kinase Kd 4.45 CHEMBL
ATP-binding cassette sub-family G member 2 Transporter IC50 5.82 CHEMBL
SRSF protein kinase 1 Kinase IC50 6.71 CHEMBL
SRSF protein kinase 2 Kinase IC50 7.55 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
Vascular endothelial growth factor receptor 2 Kinase IC50 5.85 CHEMBL

External reference:

IDSource
D10450 KEGG_DRUG
4035251 VANDF
CHEBI:90936 CHEBI
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
EMH PDB_CHEM_ID
CHEMBL3707320 ChEMBL_ID
9699 INN_ID
49806720 PUBCHEM_CID
LIJ4CT1Z3Y UNII
LIJ4CT1Z3Y INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ALECENSA HUMAN PRESCRIPTION DRUG LABEL 1 50242-130 CAPSULE 150 mg ORAL NDA 27 sections