carfilzomib indications/contra

Stem definitionDrug idCAS RN
proteasome inhibitors 4483 868540-17-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • carfilzomib
  • kyprolis
  • PR-171
  • PR 171
epoxomicin derivative proteasome inhibitor with antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells
  • Molecular weight: 719.92
  • Formula: C40H57N5O7
  • CLOGP: 6.40
  • LIPINSKI: 3
  • HAC: 12
  • HDO: 4
  • TPSA: 158.47
  • ALOGS: -5.17
  • ROTB: 20

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
July 20, 2012 FDA ONYX 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
Off label use 1193.36 39.08 464 5414 53513 3326468
Plasma cell myeloma 927.37 39.08 278 5600 14322 3365659
Fatigue 796.15 39.08 432 5446 106808 3273173
Death 633.34 39.08 423 5455 151901 3228080
Disease progression 606.50 39.08 248 5630 32011 3347970
Dyspnoea 530.20 39.08 328 5550 102606 3277375
Pneumonia 450.03 39.08 258 5620 69885 3310096
Pyrexia 410.17 39.08 256 5622 80859 3299122
Unevaluable event 389.97 39.08 141 5737 12935 3367046
Platelet count decreased 353.72 39.08 162 5716 27306 3352675
Asthenia 340.86 39.08 211 5667 65454 3314527
Neuropathy peripheral 300.44 39.08 125 5753 16682 3363299
Anaemia 282.62 39.08 175 5703 54158 3325823
Thrombocytopenia 278.00 39.08 149 5729 35119 3344862
Acute kidney injury 253.12 39.08 158 5720 49525 3330456
Cardiac failure 250.42 39.08 116 5762 19989 3359992
Diarrhoea 210.08 39.08 190 5688 104158 3275823
Nausea 207.77 39.08 208 5670 129437 3250544
Sepsis 203.59 39.08 118 5760 32255 3347726
Malaise 200.68 39.08 152 5726 65025 3314956
Atrial fibrillation 190.75 39.08 102 5776 23839 3356142
White blood cell count decreased 186.81 39.08 102 5776 24845 3355136
Cytopenia 170.03 39.08 44 5834 1284 3378697
Hypertension 167.56 39.08 111 5767 38355 3341626
Feeling abnormal 161.54 39.08 96 5782 27429 3352552
Back pain 156.69 39.08 106 5772 37899 3342082
Pancytopenia 149.30 39.08 80 5798 18740 3361241
Renal failure 148.12 39.08 97 5781 32843 3347138
Insomnia 147.67 39.08 100 5778 35798 3344183
Light chain analysis increased 146.46 39.08 28 5850 186 3379795

Pharmacologic Action:

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SourceCodeDescription
ATC L01XX45 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA MoA N0000175075 Proteasome Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
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

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 7491704 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 8129346 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 8207127 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 7491704 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 8129346 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 8207127 April 14, 2025 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS 9511109 Oct. 21, 2029 KYPROLIS IS INDICATED IN COMBINATION WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS 9511109 Oct. 21, 2029 KYPROLIS IS INDICATED IN COMBINATION WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS July 24, 2018 EXPANDED INDICATION FOR USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE PRIOR LINES OF THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS July 24, 2018 EXPANDED INDICATION FOR USE IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE PRIOR LINES OF THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS Jan. 21, 2019 AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE OR MORE LINES OF THERAPY
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS Jan. 21, 2019 REVISED INDICATION FOR USE IN COMBINATION WITH DEXAMETHASONE OR WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY.
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS Jan. 21, 2019 AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE OR MORE LINES OF THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS Jan. 21, 2019 REVISED INDICATION FOR USE IN COMBINATION WITH DEXAMETHASONE OR WITH LENALIDOMIDE PLUS DEXAMETHASONE FOR THE TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY.
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS July 20, 2019 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS July 20, 2019 TREATMENT OF PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST TWO PRIOR THERAPIES INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT AND HAVE DEMONSTRATED DISEASE PROGRESSION ON OR WITHIN 60 DAYS OF COMPLETION OF THE LAST THERAPY

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proteasome subunit beta type-5 Enzyme INHIBITOR IC50 8.22 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Cathepsin B Enzyme IC50 4.96 CHEMBL
Proteasome subunit beta type-8 Enzyme IC50 7.85 CHEMBL

External reference:

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IDSource
7420 IUPHAR_LIGAND_ID
D08880 KEGG_DRUG
4031662 VUID
N0000185509 NUI
C2001856 UMLSCUI
72X6E3J5AR UNII
8859 INN_ID
CHEMBL451887 ChEMBL_ID
C519125 MESH_SUPPLEMENTAL_RECORD_UI
DB08889 DRUGBANK_ID
C524865 MESH_SUPPLEMENTAL_RECORD_UI
1302966 RXNORM
014536 NDDF
28679 MMSL
d07882 MMSL
4031662 VANDF
N0000185509 NDFRT
713463006 SNOMEDCT_US
714783001 SNOMEDCT_US
11556711 PUBCHEM_CID
CHEBI:65347 CHEBI

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-101 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 60 mg INTRAVENOUS NDA 16 sections
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-102 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 30 mg INTRAVENOUS NDA 16 sections