ponatinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4716 943319-70-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ponatinib
  • iclusig
  • AP24534
  • ponatinib hydrochloride
  • ponatinib HCl
a pan-Bcr-Abl protein kinase Inhibitor
  • Molecular weight: 532.57
  • Formula: C29H27F3N6O
  • CLOGP: 5.77
  • LIPINSKI: 2
  • HAC: 7
  • HDO: 1
  • TPSA: 65.77
  • ALOGS: -5.26
  • ROTB: 7

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Dec. 14, 2012 FDA ARIAD

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
Acute lymphocytic leukaemia 248.57 21.98 59 5409 2714 46677880
Acute lymphocytic leukaemia recurrent 211.01 21.98 49 5419 2046 46678548
Chronic myeloid leukaemia 128.63 21.98 34 5434 2424 46678170
Chronic myeloid leukaemia recurrent 128.01 21.98 22 5446 184 46680410
Philadelphia chromosome positive 126.29 21.98 23 5445 276 46680318
Cytogenetic analysis abnormal 123.00 21.98 25 5443 551 46680043
Neoplasm progression 106.10 21.98 55 5413 26628 46653966
Blast crisis in myelogenous leukaemia 90.65 21.98 19 5449 489 46680105
Rash 82.08 21.98 148 5320 356364 46324230
Peripheral arterial occlusive disease 76.52 21.98 25 5443 3727 46676867
Dry skin 74.48 21.98 51 5417 40965 46639629
Therapeutic response delayed 61.45 21.98 14 5454 535 46680059
Stem cell transplant 53.80 21.98 16 5452 1750 46678844
Hypertension 49.47 21.98 85 5383 196271 46484323
Thrombocytopenia 46.13 21.98 65 5403 126516 46554078
Death 44.03 21.98 111 5357 335437 46345157
Chronic myeloid leukaemia transformation 42.64 21.98 8 5460 114 46680480
Catabolic state 40.78 21.98 7 5461 58 46680536
Platelet count decreased 40.40 21.98 54 5414 99970 46580624
Cytopenia 39.68 21.98 19 5449 7749 46672845
Graft versus host disease 39.49 21.98 18 5450 6570 46674024
Leukaemia recurrent 36.17 21.98 11 5457 1298 46679296
Product administered to patient of inappropriate age 35.66 21.98 13 5455 2683 46677911
Drug resistance 34.86 21.98 23 5445 17345 46663249
Blast cell crisis 34.12 21.98 6 5462 58 46680536
Pleural effusion 33.81 21.98 45 5423 82907 46597687
Ichthyosis acquired 32.21 21.98 4 5464 0 46680594
Chemotherapy 31.62 21.98 10 5458 1342 46679252
Peripheral artery stenosis 30.86 21.98 8 5460 527 46680067
Pyrexia 29.80 21.98 99 5369 348703 46331891
Lipase increased 29.27 21.98 16 5452 8587 46672007
Off label use 28.27 21.98 103 5365 379738 46300856
Soft tissue necrosis 28.10 21.98 7 5461 393 46680201
Pancytopenia 27.06 21.98 41 5427 85017 46595577
Central nervous system leukaemia 25.35 21.98 5 5463 94 46680500
Carotid artery stenosis 24.57 21.98 12 5456 5108 46675486
Capillary leak syndrome 24.54 21.98 9 5459 1888 46678706
Ischaemic stroke 23.91 21.98 18 5450 16704 46663890
Bone pain 23.15 21.98 28 5440 46862 46633732
Pancreatitis 23.10 21.98 27 5441 43600 46636994

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
Acute lymphocytic leukaemia recurrent 249.03 22.96 66 6286 2601 29943525
Acute lymphocytic leukaemia 198.78 22.96 57 6295 3015 29943111
Neoplasm progression 195.55 22.96 89 6263 17934 29928192
Chronic myeloid leukaemia 145.40 22.96 43 6309 2534 29943592
Chronic myeloid leukaemia transformation 131 22.96 24 6328 154 29945972
Drug resistance 130.40 22.96 70 6282 20063 29926063
Cytogenetic analysis abnormal 105.03 22.96 23 6329 394 29945732
Chronic myeloid leukaemia recurrent 91.62 22.96 17 6335 118 29946008
Blast crisis in myelogenous leukaemia 88.83 22.96 21 6331 513 29945613
Philadelphia chromosome positive 65.24 22.96 14 6338 217 29945909
Peripheral arterial occlusive disease 63.89 22.96 28 6324 5140 29940986
Autoimmune lymphoproliferative syndrome 63.82 22.96 13 6339 154 29945972
Blast cell crisis 52.87 22.96 10 6342 78 29946048
Loss of therapeutic response 51.49 22.96 10 6342 91 29946035
Viral haemorrhagic cystitis 51.33 22.96 15 6337 846 29945280
Lipase increased 50.12 22.96 28 6324 8648 29937478
Hepatotoxicity 46.20 22.96 35 6317 18110 29928016
Pleural effusion 46.10 22.96 67 6285 73999 29872127
Death 42.22 22.96 168 6184 357115 29589011
Stem cell transplant 41.54 22.96 16 6336 2115 29944011
Bone marrow transplant 41.15 22.96 13 6339 955 29945171
Haematopoietic stem cell mobilisation 40.26 22.96 9 6343 170 29945956
Gallbladder oedema 39.36 22.96 9 6343 189 29945937
Thrombocytopenia 36.62 22.96 86 6266 136958 29809168
Peripheral vascular disorder 36.15 22.96 19 6333 5200 29940926
Pancreatitis 35.19 22.96 41 6311 36449 29909677
Platelet count decreased 34.43 22.96 72 6280 106057 29840069
Peripheral artery stenosis 34.29 22.96 11 6341 849 29945277
Drug intolerance 34.20 22.96 45 6307 45246 29900880
Off label use 33.27 22.96 122 6230 249168 29696958
Post transplant lymphoproliferative disorder 33.05 22.96 18 6334 5288 29940838
Transplant 32.96 22.96 10 6342 642 29945484
Central nervous system leukaemia 31.76 22.96 8 6344 256 29945870
Cytopenia 30.49 22.96 20 6332 8236 29937890
Bone pain 30.32 22.96 28 6324 18998 29927128
Epstein-Barr virus infection 29.13 22.96 18 6334 6688 29939438
Clonal evolution 26.56 22.96 6 6346 119 29946007
Dry skin 26.41 22.96 28 6324 22426 29923700
Gastrointestinal wall thickening 25.68 22.96 9 6343 912 29945214
Peripheral artery occlusion 25.16 22.96 10 6342 1436 29944690
Hypertension 23.95 22.96 68 6284 121286 29824840

Pharmacologic Action:

SourceCodeDescription
ATC L01EA05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
BCR-ABL tyrosine kinase inhibitors
FDA MoA N0000175076 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:38637 tyrosine kinase inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic myeloid leukemia indication 92818009 DOID:8552
Philadelphia chromosome-positive acute lymphoblastic leukemia indication 425688002

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.98 acidic
pKa2 8.49 Basic
pKa3 5.58 Basic
pKa4 4.36 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 10MG BASE ICLUSIG TAKEDA PHARMS USA N203469 Dec. 18, 2020 RX TABLET ORAL Dec. 18, 2023 CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINULLSE INHIBITORS
EQ 15MG BASE ICLUSIG TAKEDA PHARMS USA N203469 Dec. 14, 2012 RX TABLET ORAL Dec. 18, 2023 CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINULLSE INHIBITORS
EQ 30MG BASE ICLUSIG TAKEDA PHARMS USA N203469 April 23, 2015 RX TABLET ORAL Dec. 18, 2023 CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINULLSE INHIBITORS
EQ 45MG BASE ICLUSIG TAKEDA PHARMS USA N203469 Dec. 14, 2012 RX TABLET ORAL Dec. 18, 2023 CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINULLSE INHIBITORS

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Breakpoint cluster region protein Kinase INHIBITOR CHEMBL CHEMBL
Tyrosine-protein kinase ABL1 Kinase INHIBITOR IC50 9.43 WOMBAT-PK CHEMBL
Tyrosine-protein kinase Lyn Kinase INHIBITOR IC50 9.62 WOMBAT-PK
Mast/stem cell growth factor receptor Kit Kinase INHIBITOR IC50 7.90 WOMBAT-PK
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 8.82 WOMBAT-PK
Fibroblast growth factor receptor 1 Kinase INHIBITOR IC50 8.66 WOMBAT-PK
Platelet-derived growth factor receptor alpha Kinase INHIBITOR IC50 8.96 WOMBAT-PK
Receptor-type tyrosine-protein kinase FLT3 Kinase IC50 9.52 CHEMBL
Bcr/Abl fusion protein Kinase IC50 9.30 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 7.59 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 8.52 CHEMBL
Cyclin-dependent kinase 8 Kinase INHIBITOR Kd 8.17 IUPHAR
Cyclin-dependent kinase 19 Kinase INHIBITOR Kd 7.92 IUPHAR
Tyrosine-protein kinase CSK Kinase INHIBITOR IC50 8.27 WOMBAT-PK
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 9.05 CHEMBL

External reference:

IDSource
D09950 KEGG_DRUG
4032031 VUID
N0000186141 NUI
1114544-31-8 SECONDARY_CAS_RN
4032031 VANDF
C2703109 UMLSCUI
CHEBI:78543 CHEBI
0LI PDB_CHEM_ID
CHEMBL1171837 ChEMBL_ID
CHEMBL2105708 ChEMBL_ID
24826799 PUBCHEM_CID
DB08901 DRUGBANK_ID
C545373 MESH_SUPPLEMENTAL_RECORD_UI
5890 IUPHAR_LIGAND_ID
9362 INN_ID
4340891KFS UNII
1364347 RXNORM
196462 MMSL
29016 MMSL
31534 MMSL
d07936 MMSL
014797 NDDF
014798 NDDF
703796003 SNOMEDCT_US
703797007 SNOMEDCT_US
703798002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Iclusig HUMAN PRESCRIPTION DRUG LABEL 1 63020-533 TABLET, FILM COATED 30 mg ORAL NDA 33 sections
Iclusig HUMAN PRESCRIPTION DRUG LABEL 1 63020-534 TABLET, FILM COATED 45 mg ORAL NDA 33 sections
Iclusig HUMAN PRESCRIPTION DRUG LABEL 1 63020-535 TABLET, FILM COATED 15 mg ORAL NDA 33 sections
Iclusig HUMAN PRESCRIPTION DRUG LABEL 1 63020-536 TABLET, FILM COATED 10 mg ORAL NDA 33 sections