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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4187 877399-52-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • crizotinib
  • xalkori
  • PF 02341066
  • PF-02341066
Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d'Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene's expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met.
  • Molecular weight: 450.34
  • Formula: C21H22Cl2FN5O
  • CLOGP: 4.34
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 77.99
  • ALOGS: -4.87
  • ROTB: 5
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.50 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 22.15 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 9.75 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.09 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 38.90 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 0.01 mg/mL Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 43 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.021 High 0.80
caco2-efflux Caco-2 efflux ratio (BA/AB) 23.714 High 0.80
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 6.138 10^-6 cm/s High 0.80
dh-clint Dog hepatocyte intrinsic clearance 4.887 uL/min/10^6 cells High 0.80
dppb Dog plasma protein binding (% unbound) 4.780 % High 0.80
fcs-ppb Fetal calf serum protein binding (% unbound) 13.360 % High 0.80
herg hERG pIC50 5.462 pIC50 High 0.80
hh-clint Human hepatocyte intrinsic clearance 1.746 uL/min/10^6 cells High 0.80
hlm-clint Human liver microsomal intrinsic clearance 14.322 uL/min/mg protein High 0.80
hppb Human plasma protein binding (% unbound) 6.740 % High 0.80
kinase-safety-class AAK1,ABL1,ABL2,ACVR1B,ACVR2A,ACVR2B,ACVRL1,AKT1,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK1,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK2,CDK3,CDK4,CDK5,CDK6,CDK7,CDK9,CHEK1,CLK2,CLK4,CSF1R,CSK,DDR1,DYRK1A,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB4,ERBB2,FGFR1,FGFR4,FLT1,FLT3,FLT4,FYN,GAK,GRK2,GSK3A,GSK3B,HASPIN,HIPK2,IGF1R,IKBKB,INSR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K19,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK7,MAPK9,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,MST1R,MTOR,NTRK1,NTRK2,NTRK3,NUAK1,PAK1,PAK2,PAK4,PAK5,PDGFRB,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CD,PIK3CG,PIM1,PIM2,PIM3,PRKAA1,PRKAA2,PRKCD,PRKCI,PRKDC,PTK6,RET,RIPK1,RIPK3,ROCK1,ROCK2,RPS6KA1,SGK1,SIK2,SIK3,SRC,STK10,STK17A,STK3,STK33,STK4,SYK,TEK,TGFBR1,TNIK,TTK,TYRO3,ULK1,ULK2,YES1 152
kinase-selectivity-class AAK1,ABL2,ACVR2A,ACVR2B,ACVRL1,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2A,CAMK2B,CAMK2D,CDK1,CDK9,CSF1R,DDR1,DYRK1B,EGFR,EPHA2,EPHB4,ERBB2,FGFR1,FLT3,FYN,IGF1R,INSR,IRAK1,IRAK3,JAK1,JAK2,KDR,KIT,LCK,LRRK2,LYN,MAP2K3,MAP3K1,MAP3K10,MAP3K11,MAP3K2,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAP4K5,MAPK7,MARK4,MELK,MET,MINK1,MST1R,NTRK1,NTRK3,NUAK1,PAK1,PDK4,PIK3CA,PIK3CB,PIK3CD,PRKCD,PRKDC,RET,SIK2,SIK3,SRC,STK10,STK33,STK4,SYK,TEK,TNIK,TYRO3,ULK1,ULK2,YES1 79
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 29.785 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 37.497 High 0.80
mh-clint Mouse hepatocyte intrinsic clearance 15.596 High 0.80
mppb Mouse plasma protein binding (% unbound) 4.280 High 0.80
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 82.604 High 0.80
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 1
pppb Pig plasma protein binding (% unbound) 11.580 % High 0.80
rat-kpuu-brain Rat brain Kpuu 0.016 % High 1
rh-clint Rat hepatocyte intrinsic clearance 13.709 uL/min/10^6 cells High 0.80
rh-fuinc Rat hepatocyte fraction unbound in incubation 19.930 % High 0.80
rppb Rat plasma protein binding (% unbound) 5.390 % High 0.80
solubility-dd Solubility at pH 7.4 in DMSO 356.451 uM High 0.80

Approvals:

DateAgencyCompanyOrphan
Oct. 23, 2012 EMA
Aug. 26, 2011 FDA PF PRISM CV

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 981.47 26.24 315 10484 44171 90573477
Disease progression 907.72 26.24 418 10381 156197 90461451
Death 541.18 26.24 440 10359 456111 90161537
Photopsia 264.13 26.24 70 10729 4954 90612694
Nausea 249.34 26.24 459 10340 1109857 89507791
Visual impairment 220.49 26.24 157 10642 132208 90485440
Pleural effusion 164.10 26.24 123 10676 111868 90505780
Vomiting 161.16 26.24 314 10485 787979 89829669
Dysgeusia 143.23 26.24 85 10714 52475 90565173
Oedema peripheral 140.50 26.24 163 10636 257752 90359896
Renal abscess 138.04 26.24 31 10768 1090 90616558
Diarrhoea 133.37 26.24 323 10476 938867 89678781
Oesophagitis 124.68 26.24 54 10745 17195 90600453
Constipation 113.88 26.24 153 10646 280242 90337406
Drug resistance 101.01 26.24 56 10743 30393 90587255
Vitreous floaters 86.83 26.24 33 10766 7516 90610132
Metastases to central nervous system 86.18 26.24 42 10757 17500 90600148
Interstitial lung disease 78.00 26.24 68 10731 76337 90541311
Pneumonitis 70.19 26.24 51 10748 44119 90573529
Malignant neoplasm progression 65.63 26.24 72 10727 106798 90510850
Transaminases increased 63.81 26.24 45 10754 37147 90580501
Acquired gene mutation 63.31 26.24 17 10782 1262 90616386
Dysphagia 56.08 26.24 68 10731 112210 90505438
Pericardial effusion 55.07 26.24 41 10758 36792 90580856
Vision blurred 53.79 26.24 66 10733 110227 90507421
Pulmonary embolism 52.38 26.24 71 10728 130749 90486899
Alanine aminotransferase increased 51.65 26.24 67 10732 118271 90499377
Embolism 50.50 26.24 24 10775 9457 90608191
Renal cyst 49.00 26.24 26 10773 12924 90604724
Bradycardia 45.51 26.24 53 10746 83794 90533854
Hepatotoxicity 45.16 26.24 40 10759 45802 90571846
Decreased appetite 43.18 26.24 120 10679 376420 90241228
Electrocardiogram QT prolonged 41.34 26.24 47 10752 72409 90545239
Oesophageal pain 39.32 26.24 16 10783 4358 90613290
Lung adenocarcinoma 38.82 26.24 17 10782 5548 90612100
Drug hypersensitivity 38.35 26.24 5 10794 463604 90154044
Hepatic function abnormal 37.09 26.24 36 10763 46252 90571396
Oesophageal ulcer 36.89 26.24 16 10783 5103 90612545
Hypersensitivity 32.96 26.24 7 10792 454670 90162978
Systemic lupus erythematosus 32.20 26.24 3 10796 361893 90255755
Cardiac failure 31.64 26.24 51 10748 109445 90508203
Visual brightness 30.90 26.24 5 10794 27 90617621
Oedema 30.37 26.24 71 10728 200224 90417424
Aspartate aminotransferase increased 29.82 26.24 48 10751 102889 90514759
Renal cyst infection 29.64 26.24 6 10793 127 90617521
Oesophageal candidiasis 29.54 26.24 15 10784 6814 90610834
Blood creatine phosphokinase increased 28.27 26.24 27 10772 33996 90583652
Diplopia 28.16 26.24 25 10774 28689 90588959
Neutropenia 28.07 26.24 74 10725 224830 90392818
Multiple-drug resistance 27.70 26.24 15 10784 7761 90609887
Metapneumovirus infection 27.48 26.24 9 10790 1326 90616322
Renal failure 27.46 26.24 53 10746 130954 90486694
Maternal exposure during pregnancy 27.22 26.24 5 10794 360058 90257590
Urticaria 26.76 26.24 3 10796 312731 90304917

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 705.34 26.45 399 7739 143257 42469940
Neoplasm progression 696.41 26.45 246 7892 28754 42584443
Death 458.18 26.45 500 7638 470685 42142512
Nausea 113.00 26.45 239 7899 396560 42216637
Visual impairment 108.19 26.45 79 8059 43034 42570163
Oedema peripheral 81.04 26.45 114 8024 135962 42477235
Acquired gene mutation 64.21 26.45 20 8118 1560 42611637
Vomiting 61.68 26.45 156 7982 289567 42323630
Photopsia 59.88 26.45 21 8117 2371 42610826
Interstitial lung disease 57.80 26.45 73 8065 78389 42534808
Oedema 56.22 26.45 59 8079 51942 42561255
Pneumonitis 49.92 26.45 50 8088 41668 42571529
Constipation 49.63 26.45 101 8037 162190 42451007
Diarrhoea 48.88 26.45 195 7943 460654 42152543
Metastases to central nervous system 48.23 26.45 28 8110 10327 42602870
Dysgeusia 46.57 26.45 44 8094 34145 42579052
Malignant neoplasm progression 46.38 26.45 78 8060 108322 42504875
Decreased appetite 42.03 26.45 105 8033 193032 42420165
Pleural effusion 41.67 26.45 70 8068 97096 42516101
Drug resistance 40.88 26.45 41 8097 34207 42578990
Sinus bradycardia 38.99 26.45 28 8110 14825 42598372
Oesophagitis 38.33 26.45 28 8110 15219 42597978
Hepatic function abnormal 34.84 26.45 46 8092 51521 42561676
Second primary malignancy 32.12 26.45 21 8117 9554 42603643
Hypoalbuminaemia 31.18 26.45 25 8113 15585 42597612

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 1421.60 22.58 714 16764 243320 110328501
Neoplasm progression 1300.05 22.58 458 17020 64137 110507684
Death 850.31 22.58 771 16707 698098 109873723
Nausea 303.90 22.58 626 16852 1235064 109336757
Photopsia 277.58 22.58 81 17397 6133 110565688
Visual impairment 268.35 22.58 199 17279 134229 110437592
Oedema peripheral 188.04 22.58 245 17233 328415 110243406
Pleural effusion 177.56 22.58 177 17301 177532 110394289
Vomiting 174.85 22.58 419 17059 910256 109661565
Dysgeusia 160.97 22.58 113 17365 69872 110501949
Constipation 151.52 22.58 231 17247 357555 110214266
Renal abscess 148.79 22.58 37 17441 1519 110570302
Diarrhoea 146.18 22.58 452 17026 1139053 109432768
Interstitial lung disease 132.18 22.58 135 17343 139199 110432622
Oesophagitis 128.93 22.58 71 17407 28644 110543177
Acquired gene mutation 127.86 22.58 37 17441 2717 110569104
Drug resistance 122.63 22.58 88 17390 56286 110515535
Metastases to central nervous system 112.40 22.58 60 17418 22757 110549064
Malignant neoplasm progression 110.48 22.58 137 17341 174430 110397391
Vitreous floaters 87.76 22.58 38 17440 9096 110562725
Decreased appetite 81.38 22.58 210 17268 475636 110096185
Pneumonitis 77.74 22.58 77 17401 76454 110495367
Hepatic function abnormal 71.30 22.58 79 17399 89216 110482605
Transaminases increased 70.43 22.58 67 17411 63323 110508498
Renal cyst 65.64 22.58 39 17439 18133 110553688
Sinus bradycardia 64.04 22.58 46 17432 29437 110542384
Embolism 61.57 22.58 36 17442 16253 110555568
Pericardial effusion 58.90 22.58 58 17420 57159 110514662
Alanine aminotransferase increased 56.59 22.58 103 17375 183670 110388151
Pulmonary embolism 55.93 22.58 112 17366 214362 110357459
Vision blurred 55.43 22.58 84 17394 128938 110442883
Hypoalbuminaemia 53.49 22.58 41 17437 28933 110542888
Lung adenocarcinoma 52.45 22.58 27 17451 9504 110562317
Electrocardiogram QT prolonged 51.20 22.58 74 17404 108886 110462935
Drug hypersensitivity 51 22.58 6 17472 454084 110117737
Oesophageal ulcer 51.00 22.58 25 17453 7939 110563882
Hepatotoxicity 50.44 22.58 56 17422 63344 110508477
Dysphagia 48.44 22.58 87 17391 153513 110418308
Second primary malignancy 45.81 22.58 31 17447 18037 110553784
Bradycardia 45.15 22.58 85 17393 155432 110416389
Renal impairment 43.94 22.58 94 17384 188351 110383470
Oedema 43.62 22.58 100 17378 209876 110361945
Dehydration 42.27 22.58 118 17360 279393 110292428
Aspartate aminotransferase increased 41.06 22.58 83 17395 159853 110411968
Toxicity to various agents 40.12 22.58 13 17465 480542 110091279
Renal cyst infection 38.95 22.58 9 17469 269 110571552
Multiple-drug resistance 36.67 22.58 24 17454 13211 110558610
Carcinoembryonic antigen increased 34.69 22.58 14 17464 2810 110569011
Urticaria 33.90 22.58 5 17473 318852 110252969
Hypersensitivity 33.59 22.58 11 17467 403987 110167834
Non-small cell lung cancer 31.21 22.58 18 17460 7917 110563904
Rheumatoid arthritis 31.16 22.58 5 17473 299608 110272213
Hypertension 30.14 22.58 22 17456 510062 110061759
Pain 29.72 22.58 67 17411 954888 109616933
Systemic lupus erythematosus 29.45 22.58 3 17475 254335 110317486
Arthralgia 29.19 22.58 49 17429 779583 109792238
Sinusitis 28.60 22.58 6 17472 296682 110275139
Oesophageal candidiasis 27.37 22.58 19 17459 11515 110560306
Maternal exposure during pregnancy 27.08 22.58 4 17474 254879 110316942
Diplopia 26.65 22.58 33 17445 41861 110529960
Musculoskeletal stiffness 26.28 22.58 6 17472 279816 110292005
Generalised oedema 25.94 22.58 28 17450 30676 110541145
Blister 25.52 22.58 3 17475 227373 110344448
Drug ineffective 25.51 22.58 139 17339 1520401 109051420
Pruritus 25.21 22.58 33 17445 581527 109990294
Blood creatine phosphokinase increased 25.10 22.58 43 17435 73034 110498787
Visual field defect 24.86 22.58 17 17461 10055 110561766
Blood creatinine increased 24.53 22.58 74 17404 182815 110389006
Metastases to liver 24.34 22.58 29 17449 35357 110536464
Oesophageal pain 23.90 22.58 13 17465 5112 110566709
Nasopharyngitis 23.30 22.58 17 17461 394344 110177477
Metapneumovirus infection 22.93 22.58 10 17468 2434 110569387
Neutropenia 22.69 22.58 118 17360 374502 110197319

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01ED01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA N0000020000 Receptor Tyrosine Kinase Inhibitors
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000182139 Cytochrome P450 2B6 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187061 Organic Cation Transporter 2 Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
FDA MoA N0000191265 Organic Cation Transporter 1 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:59163 biomarker
CHEBI has role CHEBI:62434 EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

L01ED Anaplastic lymphoma kinase (ALK) inhibitors 4 drugs
alectinibbrigatinibceritiniblorlatinib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Reactive oxygen species 1 positive non-small cell lung cancer indication 72242500
Non-small cell lung cancer indication 254637007 DOID:3908
Anaplastic lymphoma kinase positive anaplastic large cell lymphoma indication 738770003
Inflammatory myofibroblastic tumor (IMT), ALK-positive indication 771233008
ALK fusion gene-positive non-small-cell lung cancer indication 830151004




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.74 Basic
pKa2 6.14 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
200MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL 7825137 May 12, 2027 METHOD OF REVERSING OR INHIBITING THE PROGRESS OF UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE IN ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
200MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL 7825137 May 12, 2027 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
200MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL 7825137 May 12, 2027 TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
250MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL 7825137 May 12, 2027 METHOD OF REVERSING OR INHIBITING THE PROGRESS OF UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE IN ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
250MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL 7825137 May 12, 2027 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
250MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL 7825137 May 12, 2027 TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
150MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 METHOD OF REVERSING OR INHIBITING THE PROGRESS OF UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE IN ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
150MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
150MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
20MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 METHOD OF REVERSING OR INHIBITING THE PROGRESS OF UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE IN ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
20MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
20MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
50MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 METHOD OF REVERSING OR INHIBITING THE PROGRESS OF UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE IN ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
50MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE
50MG XALKORI PF PRISM CV N217581 Sept. 7, 2023 RX CAPSULE, PELLETS ORAL 7825137 May 12, 2027 TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
200MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL Jan. 14, 2028 TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ALK-POSITIVE
250MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL Jan. 14, 2028 TREATMENT OF PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY, SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) THAT IS ALK-POSITIVE
200MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL July 14, 2029 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER WITH UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE
250MG XALKORI PF PRISM CV N202570 Aug. 26, 2011 RX CAPSULE ORAL July 14, 2029 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER WITH UNRESECTABLE, RECURRENT, OR REFRACTORY INFLAMMATORY MYOFIBROBLASTIC TUMOR (IMT) THAT IS ALK-POSITIVE

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Hepatocyte growth factor receptor Kinase INHIBITOR Kd 9.26 CHEMBL CHEMBL
ALK tyrosine kinase receptor Kinase INHIBITOR Ki 9.13 CHEMBL CHEMBL
Macrophage-stimulating protein receptor Kinase Kd 7.60 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 8 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase Kd 6.10 CHEMBL
Epidermal growth factor receptor Kinase Kd 5.57 CHEMBL
Breakpoint cluster region protein Kinase Kd 5.61 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase Kd 6.25 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 7.52 CHEMBL
Tyrosine-protein kinase Yes Kinase Kd 6.11 CHEMBL
Tyrosine-protein kinase Fyn Kinase Kd 5.89 CHEMBL
Ephrin type-A receptor 2 Kinase Kd 7 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 6.68 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase Kd 5.89 CHEMBL
Vascular endothelial growth factor receptor 1 Kinase Kd 5.64 CHEMBL
Macrophage colony-stimulating factor 1 receptor Kinase Kd 6.68 CHEMBL
Insulin-like growth factor 1 receptor Kinase Kd 6.11 CHEMBL
Insulin receptor Kinase AGONIST Kd 6.47 CHEMBL
Fibroblast growth factor receptor 3 Kinase Kd 5.57 CHEMBL
Rho-associated protein kinase 1 Kinase Kd 5.43 CHEMBL
Tyrosine-protein kinase JAK1 Kinase Kd 6.48 CHEMBL
High affinity nerve growth factor receptor Kinase Kd 7.02 CHEMBL
Tyrosine-protein kinase JAK2 Kinase Kd 6.54 CHEMBL
Rho-associated protein kinase 2 Kinase Kd 5.48 CHEMBL
Tyrosine-protein kinase SYK Kinase Kd 5.60 CHEMBL
Angiopoietin-1 receptor Kinase Kd 6.57 CHEMBL
Ephrin type-A receptor 8 Kinase Kd 6.55 CHEMBL
AP2-associated protein kinase 1 Kinase Kd 5.64 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 6.03 CHEMBL
Cytoplasmic tyrosine-protein kinase BMX Kinase Kd 5.44 CHEMBL
LIM domain kinase 1 Kinase Kd 6.08 CHEMBL
5'-AMP-activated protein kinase catalytic subunit alpha-1 Kinase Kd 5.62 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 7.36 CHEMBL
Tyrosine-protein kinase Fer Kinase Kd 6.57 CHEMBL
Serine/threonine-protein kinase PLK4 Kinase Kd 7.22 CHEMBL
Aurora kinase C Kinase Kd 5.37 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 6.34 CHEMBL
Ephrin type-A receptor 5 Kinase Kd 6 CHEMBL
Ephrin type-A receptor 4 Kinase Kd 6.44 CHEMBL
Ephrin type-A receptor 6 Kinase Kd 7.19 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 6.17 CHEMBL
Aurora kinase A Kinase Kd 6.59 CHEMBL
Ephrin type-A receptor 3 Kinase Kd 6.15 CHEMBL
BMP-2-inducible protein kinase Kinase Kd 6.13 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 5.54 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5 Kinase Kd 7.10 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 6.05 CHEMBL
Ephrin type-B receptor 1 Kinase Kd 6.92 CHEMBL
Serine/threonine-protein kinase 4 Kinase Kd 6.24 CHEMBL
Activated CDC42 kinase 1 Kinase Kd 6.12 CHEMBL
Ephrin type-A receptor 7 Kinase Kd 6.33 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 7.74 CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 2 Kinase Kd 5.82 CHEMBL
Epithelial discoidin domain-containing receptor 1 Kinase Kd 6.29 CHEMBL
Ephrin type-B receptor 4 Kinase Kd 6.24 CHEMBL
Activin receptor type-1B Kinase Kd 6.07 CHEMBL
Activin receptor type-1 Kinase Kd 6.36 CHEMBL
Inhibitor of nuclear factor kappa-B kinase subunit beta Kinase Kd 5.26 CHEMBL
Tyrosine-protein kinase ITK/TSK Kinase Kd 5.70 CHEMBL
Tyrosine-protein kinase ZAP-70 Kinase Kd 5.38 CHEMBL
Tyrosine-protein kinase BTK Kinase Kd 5.11 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 8.11 CHEMBL
BDNF/NT-3 growth factors receptor Kinase Kd 7.43 CHEMBL
Tyrosine-protein kinase receptor TYRO3 Kinase Kd 6.10 CHEMBL
Cyclin-dependent kinase 7 Kinase Kd 6.48 CHEMBL
Serine/threonine-protein kinase D1 Kinase Kd 6 CHEMBL
Ribosomal protein S6 kinase beta-1 Kinase Kd 6.19 CHEMBL
Serine/threonine-protein kinase 3 Kinase Kd 6 CHEMBL
NUAK family SNF1-like kinase 2 Kinase Kd 6.92 CHEMBL
Non-receptor tyrosine-protein kinase TNK1 Kinase Kd 6.49 CHEMBL
Non-receptor tyrosine-protein kinase TYK2 Kinase Kd 6.68 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kinase IC50 7.96 CHEMBL
Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha Kinase Kd 5.49 CHEMBL
Protein-tyrosine kinase 2-beta Kinase Kd 6.72 CHEMBL
Serine/threonine-protein kinase RIO1 Kinase Kd 5.21 CHEMBL
Tyrosine-protein kinase receptor Tie-1 Kinase Kd 6.96 CHEMBL
NT-3 growth factor receptor Kinase Kd 7.09 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 6.07 CHEMBL
Inhibitor of nuclear factor kappa-B kinase subunit epsilon Kinase Kd 6.15 CHEMBL
LIM domain kinase 2 Kinase Kd 6.16 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 3 Kinase Kd 5.48 CHEMBL
Serine/threonine-protein kinase 26 Kinase Kd 5.55 CHEMBL
Serine/threonine-protein kinase Nek7 Kinase Kd 5.24 CHEMBL
Insulin receptor-related protein Kinase Kd 6.22 CHEMBL
Interleukin-1 receptor-associated kinase 3 Kinase Kd 7.51 CHEMBL
Serine/threonine-protein kinase RIO3 Kinase Kd 5.40 CHEMBL
Serine/threonine-protein kinase SIK2 Kinase Kd 6.70 CHEMBL
SRSF protein kinase 1 Kinase Kd 5.74 CHEMBL
Serine/threonine-protein kinase TNNI3K Kinase Kd 6.96 CHEMBL
Ankyrin repeat and protein kinase domain-containing protein 1 Kinase Kd 6.11 CHEMBL
Myotonin-protein kinase Kinase Kd 5.85 CHEMBL
Leukocyte tyrosine kinase receptor Kinase Kd 7.92 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1 Kinase Kd 7.41 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 3 Kinase Kd 7.12 CHEMBL
Aurora kinase B Kinase Kd 7.12 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 6.96 CHEMBL
Tyrosine-protein kinase Mer Kinase Kd 8.44 CHEMBL
Cyclin-dependent kinase 11B Kinase Kd 6.12 CHEMBL
Cyclin-dependent kinase 11A Kinase Kd 6.38 CHEMBL
Muscle, skeletal receptor tyrosine-protein kinase Kinase Kd 6.64 CHEMBL
Serine/threonine-protein kinase DCLK1 Kinase Kd 6.48 CHEMBL
Serine/threonine-protein kinase DCLK2 Kinase Kd 6.43 CHEMBL
Serine/threonine-protein kinase Nek9 Kinase Kd 6.10 CHEMBL
AarF domain-containing protein kinase 4 Kinase Kd 5.96 CHEMBL
Dual specificity testis-specific protein kinase 1 Kinase Kd 6.42 CHEMBL
TGF-beta receptor type-1 Kinase Kd 6 CHEMBL
Ephrin type-A receptor 1 Kinase Kd 6.85 CHEMBL
Mitogen-activated protein kinase 6 Kinase Kd 5.47 CHEMBL
Mitogen-activated protein kinase 7 Kinase Kd 6.29 CHEMBL
Serine/threonine-protein kinase D2 Kinase Kd 5.19 CHEMBL
Serine/threonine-protein kinase D3 Kinase Kd 6.29 CHEMBL
Interferon-induced, double-stranded RNA-activated protein kinase Kinase Kd 5.96 CHEMBL
Receptor-interacting serine/threonine-protein kinase 1 Kinase Kd 5.80 CHEMBL
Tyrosine-protein kinase Fes/Fps Kinase Kd 6.35 CHEMBL
Proto-oncogene tyrosine-protein kinase ROS Kinase Kd 8.39 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2 Kinase Kd 7.10 CHEMBL
Misshapen-like kinase 1 Kinase Kd 5.36 CHEMBL
Serine/threonine-protein kinase TBK1 Kinase Kd 6.16 CHEMBL
Interleukin-1 receptor-associated kinase 4 Kinase Kd 5.44 CHEMBL
Cyclin-dependent kinase-like 2 Kinase Kd 5.68 CHEMBL
Protein delta homolog 1 Membrane other Kd 6.77 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 2 Kinase Kd 5.40 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 8.22 CHEMBL
G protein-coupled receptor kinase 4 Kinase Kd 5.38 CHEMBL
Homeodomain-interacting protein kinase 4 Kinase Kd 5.44 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 7.31 CHEMBL
Mitogen-activated protein kinase kinase kinase 13 Kinase Kd 6.64 CHEMBL
Mitogen-activated protein kinase kinase kinase 2 Kinase Kd 7.14 CHEMBL
Mitogen-activated protein kinase kinase kinase 3 Kinase Kd 6.96 CHEMBL
Serine/threonine-protein kinase NIM1 Kinase Kd 5.34 CHEMBL
SRSF protein kinase 3 Kinase Kd 5.09 CHEMBL
Mitogen-activated protein kinase kinase kinase 7 Kinase Kd 5.74 CHEMBL
Serine/threonine-protein kinase TAO1 Kinase Kd 5.92 CHEMBL
Serine/threonine-protein kinase TAO3 Kinase Kd 6.31 CHEMBL
Serine/threonine-protein kinase ULK1 Kinase Kd 6 CHEMBL
Serine/threonine-protein kinase ULK2 Kinase Kd 5.80 CHEMBL
Serine/threonine-protein kinase ULK3 Kinase Kd 5.17 CHEMBL
Mitogen-activated protein kinase kinase kinase 19 Kinase Kd 6.01 CHEMBL
Mitogen-activated protein kinase kinase kinase 15 Kinase Kd 5.55 CHEMBL
Receptor-interacting serine/threonine-protein kinase 4 Kinase Kd 5.68 CHEMBL
Uncharacterized serine/threonine-protein kinase SBK3 Kinase Kd 6.62 CHEMBL
Serine/threonine-protein kinase 35 Kinase Kd 6.21 CHEMBL
Mitogen-activated protein kinase kinase kinase 1 Kinase Kd 5.96 CHEMBL
Bone morphogenetic protein receptor type-1B Kinase Kd 6.64 CHEMBL
Serine/threonine-protein kinase SBK1 Kinase Kd 5.89 CHEMBL
Peripheral plasma membrane protein CASK Kinase Kd 6.85 CHEMBL
Mitogen-activated protein kinase kinase kinase 12 Kinase Kd 6.77 CHEMBL
Serine/threonine-protein kinase TAO2 Kinase Kd 6.05 CHEMBL
Dual serine/threonine and tyrosine protein kinase Kinase Kd 6.35 CHEMBL
NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor) Kinase IC50 7.29 CHEMBL
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 Enzyme IC50 5.26 CHEMBL
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 5.17 CHEMBL
Mixed lineage kinase domain-like protein Kinase Kd 6.66 CHEMBL
Focal adhesion kinase 1 Kinase Kd 6.51 CHEMBL
Acyl-CoA dehydrogenase family member 11 Enzyme Kd 5.72 CHEMBL
Tyrosine-protein kinase JAK3 Kinase Kd 6.70 CHEMBL
Tyrosine-protein kinase ABL1 Kinase IC50 5.94 CHEMBL
Macrophage-stimulating protein receptor Kinase IC50 7.10 CHEMBL
Angiopoietin-1 receptor Kinase IC50 6.35 CHEMBL
ALK tyrosine kinase receptor Kinase IC50 7.10 CHEMBL

External reference:

IDSource
4030983 VUID
N0000183253 NUI
D09731 KEGG_DRUG
4030983 VANDF
C2974289 UMLSCUI
CHEBI:64310 CHEBI
VGH PDB_CHEM_ID
CHEMBL601719 ChEMBL_ID
D000077547 MESH_DESCRIPTOR_UI
DB08865 DRUGBANK_ID
4903 IUPHAR_LIGAND_ID
9301 INN_ID
53AH36668S UNII
11626560 PUBCHEM_CID
1148495 RXNORM
185331 MMSL
28080 MMSL
d07800 MMSL
013917 NDDF
703637000 SNOMEDCT_US
703638005 SNOMEDCT_US
53AH36668S INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Xalkori HUMAN PRESCRIPTION DRUG LABEL 1 0069-0251 CAPSULE, COATED PELLETS 20 mg ORAL NDA 30 sections
Xalkori HUMAN PRESCRIPTION DRUG LABEL 1 0069-0507 CAPSULE, COATED PELLETS 50 mg ORAL NDA 30 sections
Xalkori HUMAN PRESCRIPTION DRUG LABEL 1 0069-1500 CAPSULE, COATED PELLETS 150 mg ORAL NDA 30 sections
Xalkori HUMAN PRESCRIPTION DRUG LABEL 1 0069-8140 CAPSULE 250 mg ORAL NDA 30 sections
Xalkori HUMAN PRESCRIPTION DRUG LABEL 1 0069-8141 CAPSULE 200 mg ORAL NDA 30 sections