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

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

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 0.13 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 39.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
July 20, 2012 FDA ONYX PHARMS
July 4, 2016 PMDA Ono Pharmaceutical

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 1294.53 18.22 484 12975 43994 46628609
Intercepted product preparation error 208.91 18.22 36 13423 103 46672500
Off label use 195.03 18.22 372 13087 379469 46293134
Thrombocytopenia 152.62 18.22 185 13274 126396 46546207
Platelet count decreased 130.07 18.22 152 13307 99872 46572731
Death 122.11 18.22 286 13173 335262 46337341
Tumour lysis syndrome 117.41 18.22 52 13407 7184 46665419
Unevaluable event 117.27 18.22 101 13358 46074 46626529
Cytopenia 117.03 18.22 53 13406 7715 46664888
Plasma cell myeloma recurrent 102.96 18.22 35 13424 2372 46670231
Pneumonia 100.91 18.22 286 13173 376034 46296569
Neuropathy peripheral 87.60 18.22 119 13340 90774 46581829
Thrombotic microangiopathy 86.54 18.22 44 13415 8262 46664341
Pyrexia 76.34 18.22 247 13212 348555 46324048
Pancytopenia 73.94 18.22 106 13353 84952 46587651
Disease progression 64.07 18.22 103 13356 91197 46581406
Light chain analysis increased 63.61 18.22 20 13439 1058 46671545
Cardiac failure 62.79 18.22 95 13364 79853 46592750
Fatigue 58.06 18.22 335 13124 608362 46064241
Plasma cell leukaemia 57.58 18.22 19 13440 1174 46671429
Body dysmorphic disorder 54.13 18.22 12 13447 157 46672446
White blood cell count decreased 53.54 18.22 107 13352 112124 46560479
Neutrophil count decreased 53.04 18.22 64 13395 43362 46629241
Anaemia 51.24 18.22 176 13283 255603 46417000
Plasmacytoma 50.74 18.22 21 13438 2456 46670147
Acute kidney injury 50.52 18.22 166 13293 235689 46436914
Drug hypersensitivity 47.29 18.22 7 13452 243818 46428785
Protein total increased 43.95 18.22 19 13440 2474 46670129
Sepsis 42.87 18.22 110 13349 135904 46536699
Laboratory test abnormal 42.44 18.22 42 13417 22805 46649798
Full blood count decreased 41.58 18.22 41 13418 22170 46650433
Atypical haemolytic uraemic syndrome 41.50 18.22 12 13447 476 46672127
Joint ankylosis 39.79 18.22 12 13447 552 46672051
Posterior reversible encephalopathy syndrome 36.14 18.22 32 13427 15109 46657494
Neutropenia 35.40 18.22 106 13353 143098 46529505
Condition aggravated 34.10 18.22 14 13445 245038 46427565
Completed suicide 31.20 18.22 3 13456 145917 46526686
Infusion site extravasation 30.58 18.22 19 13440 5237 46667366
Drug ineffective 30.14 18.22 98 13361 677740 45994863
Light chain analysis abnormal 28.99 18.22 7 13452 136 46672467
Acute pulmonary oedema 27.96 18.22 21 13438 7870 46664733
Drug interaction 27.61 18.22 12 13447 203082 46469521
Infusion site pain 27.45 18.22 23 13436 10084 46662519
Arthralgia 26.62 18.22 40 13419 364563 46308040
Bone lesion 26.62 18.22 17 13442 4914 46667689
Hypertensive crisis 25.23 18.22 25 13434 13590 46659013
Renal failure 25.19 18.22 81 13378 113513 46559090
Dyspnoea 24.93 18.22 242 13217 515306 46157297
Plasma cell myeloma refractory 24.22 18.22 4 13455 8 46672595
Bone pain 22.67 18.22 45 13414 46845 46625758
Cardiac disorder 22.31 18.22 43 13416 43815 46628788
Pulmonary oedema 22.30 18.22 47 13412 51058 46621545
Haemolytic anaemia 21.91 18.22 20 13439 9822 46662781
Hepatitis B reactivation 21.76 18.22 10 13449 1504 46671099
Pulmonary hypertension 21.73 18.22 38 13421 35955 46636648
Asthenia 20.77 18.22 157 13302 310918 46361685
Thrombotic thrombocytopenic purpura 19.92 18.22 13 13446 3897 46668706
Haemolytic uraemic syndrome 19.65 18.22 11 13448 2503 46670100
Pulmonary embolism 19.34 18.22 72 13387 108513 46564090
Anxiety 18.73 18.22 15 13444 181942 46490661
Musculoskeletal stiffness 18.55 18.22 3 13456 97990 46574613
Adverse drug reaction 18.43 18.22 40 13419 44322 46628281

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 1423.52 19.36 656 15789 52806 29883227
Off label use 269.20 19.36 485 15960 248805 29687228
Intercepted product preparation error 159.46 19.36 51 16394 1475 29934558
Thrombocytopenia 130.02 19.36 253 16192 136791 29799242
Unevaluable event 129.14 19.36 120 16325 31665 29904368
Pneumonia 125.85 19.36 435 16010 333871 29602162
Plasma cell myeloma recurrent 116.13 19.36 50 16395 3364 29932669
Neuropathy peripheral 102.01 19.36 157 16288 70318 29865715
Fatigue 101.72 19.36 395 16050 320278 29615755
Cytopenia 97.03 19.36 59 16386 8197 29927836
Disease progression 95.29 19.36 163 16282 79711 29856322
Plasmacytoma 94.35 19.36 43 16402 3313 29932720
Platelet count decreased 93.37 19.36 190 16255 105939 29830094
Plasma cell leukaemia 92.90 19.36 30 16415 895 29935138
Drug interaction 92.67 19.36 4 16441 199564 29736469
Death 87.60 19.36 407 16038 356876 29579157
Thrombotic microangiopathy 77.49 19.36 52 16393 8558 29927475
Light chain analysis increased 63.03 19.36 23 16422 997 29935036
Cardiac failure 55.90 19.36 134 16311 83284 29852749
Tumour lysis syndrome 54.91 19.36 50 16395 12835 29923198
Deep vein thrombosis 51.55 19.36 107 16338 60394 29875639
Thrombotic thrombocytopenic purpura 49.52 19.36 28 16417 3397 29932636
Infusion site extravasation 45.94 19.36 24 16421 2489 29933544
Laboratory test abnormal 45.61 19.36 52 16393 17390 29918643
Pyrexia 45.23 19.36 296 16149 294193 29641840
Infusion site pain 41.96 19.36 23 16422 2627 29933406
Neutropenia 40.96 19.36 159 16286 128381 29807652
Influenza 39.61 19.36 79 16366 43319 29892714
Therapy partial responder 37.36 19.36 24 16421 3667 29932366
Cardiac disorder 36.86 19.36 73 16372 39820 29896213
Infection 36.67 19.36 110 16335 77964 29858069
White blood cell count decreased 36.38 19.36 115 16330 83832 29852201
Hypercalcaemia 35.67 19.36 39 16406 12456 29923577
Ejection fraction decreased 34.31 19.36 42 16403 15133 29920900
Dyspnoea 34.27 19.36 305 16140 332990 29603043
Condition aggravated 33.41 19.36 17 16428 137849 29798184
Bone lesion 31.24 19.36 19 16426 2638 29933395
Haemolytic uraemic syndrome 30.66 19.36 17 16428 1985 29934048
Blood immunoglobulin M increased 30.59 19.36 9 16436 195 29935838
Cerebral toxoplasmosis 29.63 19.36 15 16430 1457 29934576
Atrial fibrillation 29.09 19.36 127 16318 107997 29828036
Morganella infection 28.78 19.36 10 16435 375 29935658
Infusion site erythema 28.05 19.36 15 16430 1631 29934402
Progressive multifocal leukoencephalopathy 27.24 19.36 29 16416 8984 29927049
Protein total increased 27.03 19.36 16 16429 2114 29933919
JC virus infection 26.87 19.36 15 16430 1775 29934258
Paraproteinaemia 26.52 19.36 9 16436 314 29935719
Infusion site swelling 25.51 19.36 14 16431 1602 29934431
Leukopenia 25.29 19.36 78 16367 56081 29879952
Pancytopenia 25.27 19.36 103 16342 84949 29851084
Infusion site thrombosis 24.50 19.36 5 16440 20 29936013
Bronchopneumopathy 24.23 19.36 9 16436 410 29935623
Brain natriuretic peptide increased 24.06 19.36 19 16426 4016 29932017
Monoclonal immunoglobulin present 23.54 19.36 11 16434 897 29935136
Acute kidney injury 23.31 19.36 241 16204 273601 29662432
Hospitalisation 23.25 19.36 65 16380 44254 29891779
Haemolytic anaemia 23.10 19.36 28 16417 9982 29926051
Seizure 22.59 19.36 13 16432 98462 29837571
Bronchial haemorrhage 22.59 19.36 10 16435 719 29935314
Rhabdomyolysis 22.27 19.36 4 16441 63576 29872457
Sepsis 20.47 19.36 144 16301 146251 29789782
Pulmonary hypertension 20.25 19.36 37 16408 18999 29917034
Vascular pain 19.70 19.36 6 16439 147 29935886
Overdose 19.53 19.36 11 16434 84326 29851707

Pharmacologic Action:

SourceCodeDescription
ATC L01XG02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Proteasome inhibitors
FDA MoA N0000175075 Proteasome Inhibitors
FDA EPC N0000175604 Proteasome Inhibitor
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:52726 proteasome inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Multiple myeloma indication 109989006 DOID:9538
Relapse multiple myeloma indication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.37 acidic
pKa2 5.23 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS Sept. 28, 2021 ADDITION OF A ONCE WEEKLY DOSING REGIMEN FOR CARFILZOMIB IN COMBINULLTION WITH DEXAMETHASONE FOR 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 Sept. 28, 2021 ADDITION OF A ONCE WEEKLY DOSING REGIMEN FOR CARFILZOMIB IN COMBINULLTION WITH DEXAMETHASONE FOR 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 Sept. 28, 2021 ADDITION OF A ONCE WEEKLY DOSING REGIMEN FOR CARFILZOMIB IN COMBINULLTION WITH DEXAMETHASONE FOR PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY
10MG/VIAL KYPROLIS ONYX THERAP N202714 June 7, 2018 RX POWDER INTRAVENOUS Aug. 20, 2023 TREATMENT OF ADULT PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY IN COMBINULLTION WITH DARATUMUMAB AND DEXAMETHASONE
30MG/VIAL KYPROLIS ONYX THERAP N202714 June 3, 2016 RX POWDER INTRAVENOUS Aug. 20, 2023 TREATMENT OF ADULT PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY IN COMBINULLTION WITH DARATUMUMAB AND DEXAMETHASONE
60MG/VIAL KYPROLIS ONYX THERAP N202714 July 20, 2012 RX POWDER INTRAVENOUS Aug. 20, 2023 TREATMENT OF ADULT PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED ONE TO THREE LINES OF THERAPY IN COMBINULLTION WITH DARATUMUMAB AND DEXAMETHASONE

Bioactivity Summary:

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:

IDSource
D08880 KEGG_DRUG
4031662 VUID
N0000185509 NUI
4031662 VANDF
C2001856 UMLSCUI
CHEBI:65347 CHEBI
3BV PDB_CHEM_ID
CHEMBL451887 ChEMBL_ID
DB08889 DRUGBANK_ID
8859 INN_ID
C524865 MESH_SUPPLEMENTAL_RECORD_UI
11556711 PUBCHEM_CID
7420 IUPHAR_LIGAND_ID
C519125 MESH_SUPPLEMENTAL_RECORD_UI
72X6E3J5AR UNII
1302966 RXNORM
192152 MMSL
28679 MMSL
d07882 MMSL
014536 NDDF
713463006 SNOMEDCT_US
714783001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-101 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 60 mg INTRAVENOUS NDA 31 sections
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-102 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 30 mg INTRAVENOUS NDA 31 sections
KYPROLIS HUMAN PRESCRIPTION DRUG LABEL 1 76075-103 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 10 mg INTRAVENOUS NDA 31 sections