bortezomib indications/contra

Stem definitionDrug idCAS RN
proteasome inhibitors 391 179324-69-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • LDP-341
  • PS-341
  • bortezomib
  • velcade
  • radiciol
A pyrazine and boronic acid derivative that functions as a reversible PROTEASOME INHIBITOR. It is used as an ANTINEOPLASTIC AGENT in the treatment of MULTIPLE MYELOMA and MANTLE CELL LYMPHOMA.
  • Molecular weight: 384.24
  • Formula: C19H25BN4O4
  • CLOGP: 0.78
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 4
  • TPSA: 124.44
  • ALOGS: -3.86
  • ROTB: 9

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
May 13, 2003 FDA MILLENNIUM PHARMS

FDA Adverse Event Reporting System

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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
Neuropathy peripheral 6219.06 39.23 1625 16929 15182 3352123
Plasma cell myeloma 3245.40 39.23 950 17604 13650 3353655
Thrombocytopenia 2978.68 39.23 1103 17451 34165 3333140
Disease progression 2247.07 39.23 878 17676 31381 3335924
Pneumonia 2136.21 39.23 1066 17488 69077 3298228
Diarrhoea 2109.99 39.23 1206 17348 103142 3264163
Platelet count decreased 1795.91 39.23 715 17839 26753 3340552
Death 1758.62 39.23 1235 17319 151089 3216216
Pyrexia 1667.93 39.23 950 17604 80165 3287140
Anaemia 1428.80 39.23 750 17804 53583 3313722
Neutropenia 1376.11 39.23 627 17927 32759 3334546
Sepsis 1208.82 39.23 568 17986 31805 3335500
Constipation 1117.42 39.23 530 18024 30282 3337023
Fatigue 1084.89 39.23 806 17748 106434 3260871
Herpes zoster 1073.04 39.23 387 18167 10885 3356420
Hypotension 1015.94 39.23 581 17973 48933 3318372
Febrile neutropenia 952.82 39.23 410 18144 18565 3348740
Infection 908.12 39.23 433 18121 24969 3342336
Nausea 898.25 39.23 781 17773 128864 3238441
Asthenia 891.36 39.23 592 17962 65073 3302232
Dehydration 871.71 39.23 461 18093 33188 3334117
Tumour lysis syndrome 786.63 39.23 211 18343 2108 3365197
Dyspnoea 755.94 39.23 642 17912 102292 3265013
Vomiting 754.46 39.23 605 17949 88926 3278379
Pleural effusion 738.10 39.23 342 18212 18437 3348868
Pancytopenia 737.38 39.23 342 18212 18478 3348827
Acute kidney injury 717.15 39.23 466 18088 49217 3318088
Orthostatic hypotension 713.21 39.23 233 18321 4803 3362502
Renal failure 710.51 39.23 400 18154 32540 3334765
Atrial fibrillation 696.86 39.23 355 18199 23586 3343719

Pharmacologic Action:

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SourceCodeDescription
ATC L01XX32 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA MoA N0000175075 Proteasome Inhibitors
MeSH PA D000970 Antineoplastic Agents
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35820 antiprotozoal drug
CHEBI has role CHEBI:52726 proteasome inhibitor

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Multiple myeloma indication 109989006 DOID:9538
Mantle cell lymphoma indication 443487006
Orthostatic hypotension contraindication 28651003
Dehydration contraindication 34095006
Low blood pressure contraindication 45007003
Chronic heart failure contraindication 48447003
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Interstitial pneumonia contraindication 64667001 DOID:3082
Adult respiratory distress syndrome contraindication 67782005 DOID:11394
Pulmonary hypertension contraindication 70995007 DOID:6432
Diabetes mellitus contraindication 73211009 DOID:9351
Intestinal obstruction contraindication 81060008 DOID:8437
Prolonged QT interval contraindication 111975006
Pneumonia contraindication 233604007 DOID:552
Disease of liver contraindication 235856003 DOID:409
Syncope contraindication 271594007
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Peripheral nerve disease contraindication 302226006 DOID:574
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Posterior reversible encephalopathy syndrome contraindication 450886002
Chemotherapy-Induced Hyperuricemia contraindication

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.39 acidic
pKa2 12.09 acidic
pKa3 13.65 acidic
pKa4 2.9 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
3.5MG/VIAL VELCADE MILLENNIUM PHARMS N021602 May 13, 2003 RX INJECTABLE INTRAVENOUS, SUBCUTANEOUS Feb. 8, 2018 PEDIATRIC EXCLUSIVITY
3.5MG/VIAL VELCADE MILLENNIUM PHARMS N021602 May 13, 2003 RX INJECTABLE INTRAVENOUS, SUBCUTANEOUS April 8, 2018 PEDIATRIC EXCLUSIVITY
3.5MG/VIAL VELCADE MILLENNIUM PHARMS N021602 May 13, 2003 RX INJECTABLE INTRAVENOUS, SUBCUTANEOUS Sept. 14, 2018 PROVIDES FOR UPDATES TO THE PEDIATRIC USE SECTION BASED ON THE PEDIATRIC STUDY REPORT ENTITLED, 'A PHASE II PILOT TRIAL OF BORTEZOMIB IN COMBINATION WITH INTENSIVE RE-INDUCTION THERAPY IN CHILDREN WITH RELAPSED ACUTE LYMPHOBLASTIC LYMPHOMA (LL)'
3.5MG/VIAL VELCADE MILLENNIUM PHARMS N021602 May 13, 2003 RX INJECTABLE INTRAVENOUS, SUBCUTANEOUS March 14, 2019 PEDIATRIC EXCLUSIVITY
3.5MG/VIAL VELCADE MILLENNIUM PHARMS N021602 May 13, 2003 RX INJECTABLE INTRAVENOUS, SUBCUTANEOUS Oct. 8, 2021 TREATMENT OF PATIENTS WITH MANTLE CELL LYMPHOMA WHO HAVE NOT RECEIVED AT LEAST 1 PRIOR THERAPY
3.5MG/VIAL VELCADE MILLENNIUM PHARMS N021602 May 13, 2003 RX INJECTABLE INTRAVENOUS, SUBCUTANEOUS April 8, 2022 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proteasome subunit beta type-2 Enzyme INHIBITOR IC50 6.23 CHEMBL CHEMBL
Proteasome subunit beta type-1 Enzyme INHIBITOR IC50 7.28 CHEMBL CHEMBL
Proteasome subunit beta type-8 Enzyme INHIBITOR IC50 8.09 CHEMBL CHEMBL
Proteasome subunit beta type-5 Enzyme INHIBITOR Ki 9.26 CHEMBL CHEMBL
Proteasome subunit alpha type-1 Enzyme INHIBITOR Ki 9.21 WOMBAT-PK CHEMBL
Lysosomal protective protein Enzyme IC50 5.04 CHEMBL
Chymase Enzyme IC50 5.92 CHEMBL
Chymotrypsinogen B Enzyme Ki 6.49 CHEMBL
Nuclear factor NF-kappa-B complex Unclassified IC50 8.01 CHEMBL
Neutrophil elastase Enzyme Ki 5.64 CHEMBL
26S proteasome non-ATPase regulatory subunit 1 Cytosolic other Ki 7.74 WOMBAT-PK
Cytochrome P450 2C19 Enzyme Ki 4.74 WOMBAT-PK
PH and SEC7 domain-containing protein 1 Unclassified Ki 7.74 WOMBAT-PK
Prothrombin Enzyme Ki 4.89 CHEMBL
Cathepsin G Enzyme Ki 6.20 CHEMBL
Alpha-chymotrypsin Unclassified Ki 5.62 CHEMBL

External reference:

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IDSource
DB00188 DRUGBANK_ID
4021393 VUID
N0000148811 NUI
C1176309 UMLSCUI
6391 IUPHAR_LIGAND_ID
D03150 KEGG_DRUG
69G8BD63PP UNII
8331 INN_ID
358258 RXNORM
d04871 MMSL
17263 MMSL
398907002 SNOMEDCT_US
407097007 SNOMEDCT_US
4021393 VANDF
N0000148811 NDFRT
009985 NDDF
N0000010079 NDFRT
CHEMBL325041 ChEMBL_ID
387447 PUBCHEM_CID
D000069286 MESH_DESCRIPTOR_UI
CHEBI:52717 CHEBI
BO2 PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
VELCADE HUMAN PRESCRIPTION DRUG LABEL 1 63020-049 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 3.50 mg INTRAVENOUS NDA 19 sections
Bortezomib HUMAN PRESCRIPTION DRUG LABEL 1 63323-721 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1 mg INTRAVENOUS NDA 17 sections