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

Stem definitionDrug idCAS RN
proteasome inhibitors 5067 1072833-77-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ixazomib
  • ixazomib citrate
  • MLN2238
  • MLN9708
  • ninlaro
an oral proteasome inhibitor with antineoplastic activity; MLN2238 is the biologically active form of MLN9708
  • Molecular weight: 361.03
  • Formula: C14H19BCl2N2O4
  • CLOGP: 1.10
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 4
  • TPSA: 98.66
  • ALOGS: -4.47
  • ROTB: 7

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 3.61 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 97 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 30, 2017 PMDA Takeda Pharmaceutical Company Limited
Nov. 21, 2016 EMA Takeda Pharma A/S
Nov. 20, 2015 FDA MILLENNIUM PHARMS

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
Plasma cell myeloma 1503.16 21.08 564 15270 43914 46626314
Diarrhoea 579.61 21.08 818 15016 558784 46111444
Neuropathy peripheral 381.75 21.08 285 15549 90608 46579620
Death 360.16 21.08 501 15333 335047 46335181
Adverse event 277.53 21.08 162 15672 34022 46636206
Thrombocytopenia 198.41 21.08 229 15605 126352 46543876
Platelet count decreased 187.86 21.08 199 15635 99825 46570403
Pneumonia 180.02 21.08 394 15440 375926 46294302
Off label use 160.80 21.08 379 15455 379462 46290766
Plasma cell myeloma recurrent 148.44 21.08 48 15786 2359 46667869
Product physical issue 98.38 21.08 43 15791 4884 46665344
No adverse event 98 21.08 86 15748 34145 46636083
White blood cell count decreased 94.17 21.08 150 15684 112081 46558147
Full blood count decreased 84.89 21.08 66 15768 22145 46648083
Nausea 81.91 21.08 452 15382 687002 45983226
Adverse drug reaction 79.13 21.08 86 15748 44276 46625952
Constipation 75.70 21.08 176 15658 173921 46496307
Laboratory test abnormal 74.78 21.08 62 15772 22785 46647443
Cytopenia 68.78 21.08 39 15795 7729 46662499
Influenza 62.39 21.08 110 15724 89160 46581068
Neutrophil count decreased 61.92 21.08 75 15759 43351 46626877
Product dose omission issue 57.10 21.08 155 15679 168365 46501863
Vomiting 55.14 21.08 300 15534 452494 46217734
Fatigue 53.78 21.08 371 15463 608326 46061902
Rash 41.82 21.08 234 15600 356278 46313950
Peripheral swelling 38.95 21.08 130 15704 157941 46512287
Plasmacytoma 38.01 21.08 18 15816 2459 46667769
Dehydration 37.36 21.08 129 15705 159411 46510817
Drug ineffective 36.36 21.08 114 15720 677724 45992504
Drug interaction 36.01 21.08 12 15822 203082 46467146
Toxicity to various agents 33.43 21.08 15 15819 211751 46458477
Product packaging quantity issue 33.05 21.08 13 15821 1131 46669097
Body dysmorphic disorder 31.57 21.08 8 15826 161 46670067
Arthralgia 30.42 21.08 48 15786 364555 46305673
Vitiligo 30.23 21.08 12 15822 1069 46669159
Asthenia 29.92 21.08 194 15640 310881 46359347
Neutropenia 29.44 21.08 111 15723 143093 46527135
Plasma cell leukaemia 29.09 21.08 12 15822 1181 46669047
Paraesthesia 28.38 21.08 96 15738 117341 46552887
Cataract 27.94 21.08 53 15781 45362 46624866
Accidental exposure to product 27.76 21.08 35 15799 21046 46649182
VIth nerve paresis 26.06 21.08 6 15828 79 46670149
Muscle spasms 25.77 21.08 96 15738 123017 46547211
Product blister packaging issue 25.60 21.08 7 15827 191 46670037
Drug hypersensitivity 24.47 21.08 28 15806 243797 46426431
Light chain analysis increased 23.46 21.08 10 15824 1068 46669160
Hypoglossal nerve paresis 23.43 21.08 6 15828 126 46670102
Depression 22.54 21.08 15 15819 170089 46500139
Tumour lysis syndrome 22.35 21.08 19 15815 7217 46663011
Blood immunoglobulin G increased 22.31 21.08 10 15824 1204 46669024
Joint ankylosis 22.06 21.08 8 15826 556 46669672
Blood potassium decreased 21.68 21.08 43 15791 38020 46632208
Condition aggravated 21.63 21.08 31 15803 245021 46425207
Hypertension 21.43 21.08 21 15813 196335 46473893

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
Plasma cell myeloma 1676.35 21.70 712 14080 52750 29884936
Death 372.46 21.70 643 14149 356640 29581046
Neuropathy peripheral 344.88 21.70 282 14510 70193 29867493
Pneumonia 285.77 21.70 553 14239 333753 29603933
Adverse event 241.93 21.70 128 14664 15213 29922473
Off label use 239.25 21.70 434 14358 248856 29688830
Diarrhoea 194.49 21.70 474 14318 333629 29604057
No adverse event 154.20 21.70 100 14692 17319 29920367
Thrombocytopenia 153.47 21.70 256 14536 136788 29800898
Plasma cell myeloma recurrent 149.00 21.70 58 14734 3356 29934330
Product physical issue 139.37 21.70 49 14743 2125 29935561
Platelet count decreased 133.34 21.70 209 14583 105920 29831766
Full blood count decreased 119.26 21.70 82 14710 15635 29922051
Laboratory test abnormal 109.32 21.70 81 14711 17361 29920325
Influenza 94.92 21.70 112 14680 43286 29894400
Drug interaction 82.04 21.70 4 14788 199564 29738122
Adverse drug reaction 81.46 21.70 77 14715 23068 29914618
Rash 69.33 21.70 230 14562 191659 29746027
Constipation 64.79 21.70 160 14632 112746 29824940
Fatigue 64.36 21.70 320 14472 320353 29617333
White blood cell count decreased 62.61 21.70 132 14660 83815 29853871
Toxicity to various agents 60.58 21.70 8 14784 177175 29760511
Product dose omission issue 60.30 21.70 137 14655 91494 29846192
Cytopenia 55.46 21.70 40 14752 8216 29929470
Peripheral swelling 55.08 21.70 104 14688 60970 29876716
Light chain analysis increased 50.49 21.70 19 14773 1001 29936685
Accidental exposure to product 44.14 21.70 38 14754 10077 29927609
Monoclonal immunoglobulin present 41.65 21.70 16 14776 892 29936794
Product blister packaging issue 37.66 21.70 8 14784 46 29937640
Back pain 36.94 21.70 123 14669 102473 29835213
Product packaging quantity issue 34.58 21.70 13 14779 683 29937003
Morganella infection 33.83 21.70 11 14781 374 29937312
Thrombosis 29.81 21.70 65 14727 42166 29895520
Product packaging issue 27.64 21.70 10 14782 471 29937215
Bronchial haemorrhage 26.98 21.70 11 14781 718 29936968
Plasmacytoma 26.60 21.70 18 14774 3338 29934348
Muscle spasms 26.28 21.70 81 14711 64757 29872929
Tachycardia 25.97 21.70 3 14789 73736 29863950
Product use in unapproved indication 25.94 21.70 3 14789 73690 29863996
Full blood count increased 25.69 21.70 11 14781 812 29936874
Hypertension 24.22 21.70 15 14777 121339 29816347
Laryngeal cancer metastatic 23.96 21.70 6 14786 77 29937609
Nasopharyngitis 23.36 21.70 73 14719 58776 29878910
Hypotension 22.90 21.70 40 14752 200525 29737161
Hospitalisation 22.44 21.70 60 14732 44259 29893427
Otitis externa bacterial 22.07 21.70 4 14788 8 29937678
COVID-19 22.06 21.70 35 14757 17843 29919843
Alanine aminotransferase increased 21.75 21.70 5 14787 74271 29863415

Pharmacologic Action:

SourceCodeDescription
ATC L01XG03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Proteasome inhibitors
FDA MoA N0000175075 Proteasome Inhibitors
FDA EPC N0000175604 Proteasome Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:50266 prodrugs
CHEBI has role CHEBI:52726 proteasome inhibitors
CHEBI has role CHEBI:68495 type i programmed cell-death inducer
CHEBI has role CHEBI:71031 orphan drugs
CHEBI has role CHEBI:49103 drug metabolites

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Multiple myeloma indication 109989006 DOID:9538

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.27 acidic
pKa2 12.17 acidic
pKa3 13.45 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 2.3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL Nov. 20, 2022 USE IN COMBINULLTION WITH LENULLLIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 3MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL Nov. 20, 2022 USE IN COMBINULLTION WITH LENULLLIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY
EQ 4MG BASE NINLARO TAKEDA PHARMS USA N208462 Nov. 20, 2015 RX CAPSULE ORAL Nov. 20, 2022 USE IN COMBINULLTION WITH LENULLLIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proteasome subunit beta type-5 Enzyme INHIBITOR IC50 8.47 SCIENTIFIC LITERATURE DRUG LABEL
Proteasome subunit beta type-2 Enzyme INHIBITOR IC50 5.46 SCIENTIFIC LITERATURE
Proteasome subunit beta type-1 Enzyme INHIBITOR IC50 7.51 SCIENTIFIC LITERATURE

External reference:

IDSource
D10130 KEGG_DRUG
1239908-20-3 SECONDARY_CAS_RN
4035138 VANDF
C3273711 UMLSCUI
CHEBI:90942 CHEBI
6V8 PDB_CHEM_ID
CHEMBL2141296 ChEMBL_ID
CHEMBL3545432 ChEMBL_ID
DB09570 DRUGBANK_ID
C548400 MESH_SUPPLEMENTAL_RECORD_UI
C000595706 MESH_SUPPLEMENTAL_RECORD_UI
8450 IUPHAR_LIGAND_ID
9411 INN_ID
71050168A2 UNII
25183872 PUBCHEM_CID
1723734 RXNORM
237159 MMSL
31293 MMSL
d08398 MMSL
016599 NDDF
016600 NDDF
715256005 SNOMEDCT_US
781324002 SNOMEDCT_US
784168005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-078 CAPSULE 2.30 mg ORAL NDA 29 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-079 CAPSULE 3 mg ORAL NDA 29 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-080 CAPSULE 4 mg ORAL NDA 29 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-230 CAPSULE 2.30 mg ORAL NDA 30 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-390 CAPSULE 3 mg ORAL NDA 30 sections
NINLARO HUMAN PRESCRIPTION DRUG LABEL 1 63020-400 CAPSULE 4 mg ORAL NDA 30 sections