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Identification
NameCarfilzomib
Accession NumberDB08889
TypeSmall Molecule
GroupsApproved
DescriptionCarfilzomib is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptidyl epoxide and an analog of epoxomicin. It is also a selective proteasome inhibitor. FDA approved on July 20, 2012.
Structure
Thumb
Synonyms
Kyprolis
PR-171
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KyprolisPowder, for solution60 mgIntravenousAmgen Canada Inc2016-02-11Not applicableCanada
KyprolisInjection, powder, lyophilized, for solution60 mg/30mLIntravenousOnyx Pharmaceuticals, Inc.2012-07-20Not applicableUs
KyprolisInjection, powder, lyophilized, for solution30 mg/15mLIntravenousOnyx Pharmaceuticals, Inc.2016-07-15Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII72X6E3J5AR
CAS number868540-17-4
WeightAverage: 719.9099
Monoisotopic: 719.425799203
Chemical FormulaC40H57N5O7
InChI KeyBLMPQMFVWMYDKT-NZTKNTHTSA-N
InChI
InChI=1S/C40H57N5O7/c1-27(2)22-32(36(47)40(5)26-52-40)42-39(50)34(24-30-14-10-7-11-15-30)44-38(49)33(23-28(3)4)43-37(48)31(17-16-29-12-8-6-9-13-29)41-35(46)25-45-18-20-51-21-19-45/h6-15,27-28,31-34H,16-26H2,1-5H3,(H,41,46)(H,42,50)(H,43,48)(H,44,49)/t31-,32-,33-,34-,40+/m0/s1
IUPAC Name
(2S)-4-methyl-N-[(1S)-1-{[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]carbamoyl}-2-phenylethyl]-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]-4-phenylbutanamido]pentanamide
SMILES
CC(C)C[[email protected]](NC(=O)[[email protected]](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1
Pharmacology
IndicationCarfilzomib is indicated for the 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. Approval is based on response rate.
Structured Indications
PharmacodynamicsIntravenous carfilzomib administration resulted in suppression of proteasome chymotrypsin-like activity when measured in blood 1 hour after the first dose. On Day 1 of Cycle 1, proteasome inhibition in peripheral blood mononuclear cells (PBMCs) ranged from 79% to 89% at 15 mg/m2, and from 82% to 83% at 20 mg/m2. In addition, carfilzomib administration resulted in inhibition of the LMP2 and MECL1 subunits of the immunoproteasome ranging from 26% to 32% and 41% to 49%, respectively, at 20 mg/m2. Proteasome inhibition was maintained for ≥ 48 hours following the first dose of carfilzomib for each week of dosing. Resistance against carfilzomib has been observed and although the mechanism has not been confirmed, it is thought that up-regulation of P-glycoprotein may be a contributing factor. Furthermore, studies suggest that carfilzomib is more potent than bortezomib.
Mechanism of actionCarfilzomib is made up of four modified peptides and acts as a proteasome inhibitor. Carfilzomib irreversibly and selectively binds to N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. This 20S core has 3 catalytic active sites: the chymotrypsin, trypsin, and caspase-like sites. Inhibition of the chymotrypsin-like site by carfilzomib (β5 and β5i subunits) is the most effective target in decreasing cellular proliferation, ultimately resulting in cell cycle arrest and apoptosis of cancerous cells. At higher doses, carfilzomib will inhibit the trypsin-and capase-like sites.
TargetKindPharmacological actionActionsOrganismUniProt ID
Proteasome subunit beta type-5Proteinyes
inhibitor
HumanP28074 details
Proteasome subunit beta type-8Proteinyes
inhibitor
HumanP28062 details
Proteasome subunit beta type-1Proteinyes
inhibitor
HumanP20618 details
Proteasome subunit beta type-9Proteinyes
inhibitor
HumanP28065 details
Proteasome subunit beta type-2Proteinyes
inhibitor
HumanP49721 details
Proteasome subunit beta type-10Proteinyes
inhibitor
HumanP40306 details
Related Articles
AbsorptionCmax, single IV dose of 27 mg/m^2 = 4232 ng/mL; AUC, single IV dose of 27 mg/m^2 = 379 ng•hr/mL; Carfilzomib does not accumulation in the systemic. At doses between 20 and 36 mg/m2, there was a dose-dependent increase in exposure.
Volume of distribution

Vd, steady state, 20 mg/m^2 = 28 L

Protein bindingOver the concentration range of 0.4 - 4 micromolar, carfilzomib was 97% protein bound.
Metabolism

Carfilzomib was rapidly and extensively metabolized by the liver. The predominant metabolites were the peptide fragments and the diol of carfilzomib which suggests that the main metabolic pathways are peptidase cleavage and epoxide hydrolysis. The cytochrome P450 enzyme system is minimally involved in the metabolism of carfilzomib. All metabolites are inactive.

Route of eliminationNot Available
Half lifeFollowing intravenous administration of doses ≥ 15 mg/m^2, carfilzomib was rapidly cleared from the systemic circulation with a half-life of ≤ 1 hour on Day 1 of Cycle 1.
Clearance

Systemic clearance = 151 – 263 L/hour. As this value exceeds hepatic blood flow, it suggests that carfilozmib is cleared extrahepatically.

ToxicityMost commonly reported adverse reactions (incidence ≥ 30%) are fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. The two dose limiting toxicities are thrombocytopenia and febrile neutropenia. Maximum tolerate dose = 15 mg/m^2
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Carfilzomib can be increased when it is combined with Acetaminophen.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Carfilzomib.Approved
AfatinibThe serum concentration of Carfilzomib can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Carfilzomib can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Carfilzomib can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Carfilzomib can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Carfilzomib can be increased when it is combined with Alfentanil.Approved, Illicit
AmantadineThe serum concentration of Carfilzomib can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Carfilzomib can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe serum concentration of Carfilzomib can be decreased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Carfilzomib can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Carfilzomib can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Carfilzomib can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Carfilzomib can be increased when it is combined with Amsacrine.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Carfilzomib.Investigational
AstemizoleThe serum concentration of Carfilzomib can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Carfilzomib can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Carfilzomib can be increased when it is combined with Atenolol.Approved
AtorvastatinThe serum concentration of Carfilzomib can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Carfilzomib can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Carfilzomib can be increased when it is combined with Azithromycin.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Carfilzomib.Investigational
BenzocaineThe serum concentration of Carfilzomib can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Carfilzomib can be increased when it is combined with Bepridil.Approved, Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Carfilzomib.Approved, Investigational
BiperidenThe serum concentration of Carfilzomib can be increased when it is combined with Biperiden.Approved
BosutinibThe serum concentration of Carfilzomib can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Carfilzomib can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Carfilzomib can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Carfilzomib can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Carfilzomib.Approved
CaffeineThe serum concentration of Carfilzomib can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Carfilzomib can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Carfilzomib can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Carfilzomib can be increased when it is combined with Captopril.Approved
CarbamazepineThe serum concentration of Carfilzomib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Carfilzomib can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Carfilzomib can be increased when it is combined with Caspofungin.Approved
ChloroquineThe serum concentration of Carfilzomib can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Carfilzomib can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Carfilzomib can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Carfilzomib can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Carfilzomib can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Carfilzomib can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Carfilzomib can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Carfilzomib can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Carfilzomib can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Carfilzomib can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Carfilzomib can be increased when it is combined with Clarithromycin.Approved
ClofazimineThe serum concentration of Carfilzomib can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Carfilzomib can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe serum concentration of Carfilzomib can be decreased when it is combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Clozapine.Approved
CobicistatThe serum concentration of Carfilzomib can be increased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Carfilzomib can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Carfilzomib can be increased when it is combined with Colforsin.Experimental
CrizotinibThe serum concentration of Carfilzomib can be increased when it is combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Carfilzomib.Approved, Investigational
CyclosporineThe serum concentration of Carfilzomib can be decreased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DaclatasvirThe serum concentration of Carfilzomib can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Carfilzomib can be increased when it is combined with Dactinomycin.Approved
DasatinibThe serum concentration of Carfilzomib can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Carfilzomib can be decreased when it is combined with Daunorubicin.Approved
DesipramineThe serum concentration of Carfilzomib can be increased when it is combined with Desipramine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Carfilzomib.Approved
DesloratadineThe serum concentration of Carfilzomib can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Carfilzomib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Carfilzomib can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Carfilzomib can be increased when it is combined with Diclofenac.Approved, Vet Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Carfilzomib.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Carfilzomib.Approved
DihydroergotamineThe serum concentration of Carfilzomib can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Carfilzomib can be increased when it is combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Carfilzomib can be increased when it is combined with Dipyridamole.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Carfilzomib.Approved, Investigational
DoxazosinThe serum concentration of Carfilzomib can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Carfilzomib can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Carfilzomib can be decreased when it is combined with Doxorubicin.Approved, Investigational
DronabinolThe serum concentration of Carfilzomib can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Carfilzomib can be increased when it is combined with Dronedarone.Approved
ElbasvirThe serum concentration of Carfilzomib can be increased when it is combined with Elbasvir.Approved
EnalaprilThe serum concentration of Carfilzomib can be increased when it is combined with Enalapril.Approved, Vet Approved
EnzalutamideThe serum concentration of Carfilzomib can be increased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Carfilzomib can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Carfilzomib can be increased when it is combined with Ergotamine.Approved
ErythromycinThe serum concentration of Carfilzomib can be decreased when it is combined with Erythromycin.Approved, Vet Approved
EstramustineThe serum concentration of Carfilzomib can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Carfilzomib can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Carfilzomib can be decreased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Carfilzomib can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Carfilzomib can be increased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Carfilzomib can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Carfilzomib can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Carfilzomib can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Carfilzomib can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Fluconazole.Approved
FluoxetineThe serum concentration of Carfilzomib can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Carfilzomib can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Carfilzomib can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Carfilzomib can be increased when it is combined with Flurazepam.Approved, Illicit
FluvoxamineThe serum concentration of Carfilzomib can be increased when it is combined with Fluvoxamine.Approved, Investigational
GefitinibThe serum concentration of Carfilzomib can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Carfilzomib can be increased when it is combined with Genistein.Investigational
GlyburideThe serum concentration of Carfilzomib can be increased when it is combined with Glyburide.Approved
GlycerolThe serum concentration of Carfilzomib can be increased when it is combined with Glycerol.Experimental
Gramicidin DThe serum concentration of Carfilzomib can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Carfilzomib can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Carfilzomib can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Carfilzomib can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IdelalisibThe serum concentration of Carfilzomib can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Carfilzomib can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Carfilzomib can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Carfilzomib can be decreased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Carfilzomib can be increased when it is combined with Indomethacin.Approved, Investigational
IsavuconazoniumThe serum concentration of Carfilzomib can be increased when it is combined with Isavuconazonium.Approved, Investigational
ItraconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Carfilzomib can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Carfilzomib can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Carfilzomib can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Carfilzomib can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Carfilzomib can be increased when it is combined with Lapatinib.Approved, Investigational
LevofloxacinThe serum concentration of Carfilzomib can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Carfilzomib can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Carfilzomib can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Carfilzomib can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Carfilzomib can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Carfilzomib can be increased when it is combined with Lisinopril.Approved, Investigational
LomitapideThe serum concentration of Carfilzomib can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Carfilzomib can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Carfilzomib can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Carfilzomib can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Carfilzomib can be increased when it is combined with Losartan.Approved
LovastatinThe serum concentration of Carfilzomib can be increased when it is combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Carfilzomib can be decreased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Carfilzomib can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Carfilzomib can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Carfilzomib can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Carfilzomib can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Carfilzomib can be increased when it is combined with Meprobamate.Approved, Illicit
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Carfilzomib.Withdrawn
MethadoneThe serum concentration of Carfilzomib can be increased when it is combined with Methadone.Approved
MetoprololThe serum concentration of Carfilzomib can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Carfilzomib can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Carfilzomib can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Carfilzomib can be decreased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Carfilzomib can be increased when it is combined with Mitomycin.Approved
MitoxantroneThe serum concentration of Carfilzomib can be decreased when it is combined with Mitoxantrone.Approved, Investigational
MorphineThe serum concentration of Carfilzomib can be increased when it is combined with Morphine.Approved, Investigational
NaltrexoneThe serum concentration of Carfilzomib can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Carfilzomib can be increased when it is combined with Naringenin.Experimental
NefazodoneThe serum concentration of Carfilzomib can be decreased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Carfilzomib can be decreased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Carfilzomib can be increased when it is combined with Neostigmine.Approved, Vet Approved
NicardipineThe serum concentration of Carfilzomib can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Carfilzomib can be decreased when it is combined with Nifedipine.Approved
NilotinibThe serum concentration of Carfilzomib can be increased when it is combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Carfilzomib can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Carfilzomib can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Carfilzomib can be increased when it is combined with Nitrendipine.Approved
NorethisteroneThe serum concentration of Carfilzomib can be decreased when it is combined with Norethisterone.Approved
OmeprazoleThe serum concentration of Carfilzomib can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OuabainOuabain may decrease the cardiotoxic activities of Carfilzomib.Approved
P-NitrophenolThe serum concentration of Carfilzomib can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Carfilzomib.Approved, Vet Approved
Palmitic AcidThe serum concentration of Carfilzomib can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Carfilzomib can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Carfilzomib can be increased when it is combined with Paroxetine.Approved, Investigational
PerindoprilThe serum concentration of Carfilzomib can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe serum concentration of Carfilzomib can be decreased when it is combined with Phenobarbital.Approved
PimozideThe serum concentration of Carfilzomib can be increased when it is combined with Pimozide.Approved
Platelet Activating FactorThe serum concentration of Carfilzomib can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Carfilzomib can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Carfilzomib can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Carfilzomib can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Carfilzomib can be increased when it is combined with Prednisone.Approved, Vet Approved
ProbenecidThe serum concentration of Carfilzomib can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Carfilzomib can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Carfilzomib can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Carfilzomib can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Carfilzomib can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Carfilzomib can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Carfilzomib can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Carfilzomib can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Carfilzomib can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Carfilzomib can be increased when it is combined with Quinine.Approved
RanitidineThe serum concentration of Carfilzomib can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Carfilzomib can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Carfilzomib can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Carfilzomib can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Carfilzomib can be decreased when it is combined with Reserpine.Approved
RifampicinThe serum concentration of Carfilzomib can be decreased when it is combined with Rifampicin.Approved
RilpivirineThe serum concentration of Carfilzomib can be increased when it is combined with Rilpivirine.Approved
RitonavirThe serum concentration of Carfilzomib can be decreased when it is combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Carfilzomib can be increased when it is combined with Rolapitant.Approved
SaquinavirThe serum concentration of Carfilzomib can be decreased when it is combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Carfilzomib can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Carfilzomib can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Carfilzomib can be increased when it is combined with Sertraline.Approved
SimeprevirThe serum concentration of Carfilzomib can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Carfilzomib can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Carfilzomib can be decreased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Carfilzomib can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Carfilzomib can be increased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Carfilzomib can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Carfilzomib can be increased when it is combined with Staurosporine.Experimental
StreptozocinThe serum concentration of Carfilzomib can be decreased when it is combined with Streptozocin.Approved
SulfinpyrazoneThe serum concentration of Carfilzomib can be increased when it is combined with Sulfinpyrazone.Approved
SumatriptanThe serum concentration of Carfilzomib can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Carfilzomib can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Carfilzomib can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Carfilzomib can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Carfilzomib can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Carfilzomib can be increased when it is combined with Taurocholic Acid.Experimental
TelmisartanThe serum concentration of Carfilzomib can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Carfilzomib can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Carfilzomib can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Carfilzomib can be increased when it is combined with Terfenadine.Withdrawn
TesmilifeneThe serum concentration of Carfilzomib can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Carfilzomib can be increased when it is combined with Testosterone.Approved, Investigational
TicagrelorThe serum concentration of Carfilzomib can be increased when it is combined with Ticagrelor.Approved
TolvaptanThe serum concentration of Carfilzomib can be increased when it is combined with Tolvaptan.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Carfilzomib.Approved, Investigational
TrazodoneThe serum concentration of Carfilzomib can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Carfilzomib can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Carfilzomib can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Carfilzomib can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Carfilzomib can be increased when it is combined with Trimipramine.Approved
TroleandomycinThe serum concentration of Carfilzomib can be increased when it is combined with Troleandomycin.Approved
VenlafaxineThe serum concentration of Carfilzomib can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Carfilzomib can be decreased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Carfilzomib can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Carfilzomib can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Carfilzomib can be increased when it is combined with Vinorelbine.Approved, Investigational
ZimelidineThe serum concentration of Carfilzomib can be increased when it is combined with Zimelidine.Withdrawn
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Kortuem KM, Stewart AK: Carfilzomib. Blood. 2013 Feb 7;121(6):893-7. doi: 10.1182/blood-2012-10-459883. [PubMed:23393020 ]
  2. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25. [PubMed:17591945 ]
External Links
ATC CodesL01XX45
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (310 KB)
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7982
Blood Brain Barrier-0.8941
Caco-2 permeable-0.6924
P-glycoprotein substrateSubstrate0.9378
P-glycoprotein inhibitor IInhibitor0.8224
P-glycoprotein inhibitor IINon-inhibitor0.9045
Renal organic cation transporterNon-inhibitor0.8642
CYP450 2C9 substrateNon-substrate0.8812
CYP450 2D6 substrateNon-substrate0.7587
CYP450 3A4 substrateSubstrate0.6641
CYP450 1A2 substrateNon-inhibitor0.9031
CYP450 2C9 inhibitorNon-inhibitor0.8546
CYP450 2D6 inhibitorNon-inhibitor0.7152
CYP450 2C19 inhibitorNon-inhibitor0.6665
CYP450 3A4 inhibitorInhibitor0.6532
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9676
Ames testNon AMES toxic0.7119
CarcinogenicityNon-carcinogens0.8431
BiodegradationNot ready biodegradable0.9942
Rat acute toxicity2.6381 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9831
hERG inhibition (predictor II)Non-inhibitor0.6044
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous30 mg/15mL
Injection, powder, lyophilized, for solutionIntravenous60 mg/30mL
Powder, for solutionIntravenous60 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7232818 No2005-04-142025-04-14Us
US7417042 No2006-06-072026-06-07Us
US7491704 No2005-04-142025-04-14Us
US7737112 No2007-12-072027-12-07Us
US8129346 No2006-12-252026-12-25Us
US8207125 No2005-04-142025-04-14Us
US8207126 No2005-04-142025-04-14Us
US8207127 No2005-04-142025-04-14Us
US8207297 No2005-04-142025-04-14Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA
pKa3.5FDA
Predicted Properties
PropertyValueSource
Water Solubility0.00484 mg/mLALOGPS
logP3.21ALOGPS
logP4.2ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)11.91ChemAxon
pKa (Strongest Basic)4.96ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area158.47 Å2ChemAxon
Rotatable Bond Count20ChemAxon
Refractivity198.02 m3·mol-1ChemAxon
Polarizability79.44 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPeptides
Alternative Parents
Substituents
  • Alpha peptide
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Phenylpropylamine
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Fatty acyl
  • Benzenoid
  • Oxazinane
  • N-acyl-amine
  • Morpholine
  • Fatty amide
  • Monocyclic benzene moiety
  • Alpha-aminoketone
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Ketone
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Oxirane
  • Dialkyl ether
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Threonine-type endopeptidase activity
Specific Function:
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This unit is responsible of the chymotrypsin-like activity of the proteasome and is one of the principal target of the proteasome in...
Gene Name:
PSMB5
Uniprot ID:
P28074
Molecular Weight:
28480.01 Da
References
  1. Kortuem KM, Stewart AK: Carfilzomib. Blood. 2013 Feb 7;121(6):893-7. doi: 10.1182/blood-2012-10-459883. [PubMed:23393020 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Threonine-type endopeptidase activity
Specific Function:
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the cap...
Gene Name:
PSMB8
Uniprot ID:
P28062
Molecular Weight:
30354.035 Da
References
  1. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25. [PubMed:17591945 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Threonine-type endopeptidase activity
Specific Function:
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.
Gene Name:
PSMB1
Uniprot ID:
P20618
Molecular Weight:
26489.09 Da
References
  1. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25. [PubMed:17591945 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Threonine-type endopeptidase activity
Specific Function:
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the cap...
Gene Name:
PSMB9
Uniprot ID:
P28065
Molecular Weight:
23264.1 Da
References
  1. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25. [PubMed:17591945 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Threonine-type endopeptidase activity
Specific Function:
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit has a trypsin-like activity.
Gene Name:
PSMB2
Uniprot ID:
P49721
Molecular Weight:
22836.02 Da
References
  1. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25. [PubMed:17591945 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Threonine-type endopeptidase activity
Specific Function:
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides.
Gene Name:
PSMB10
Uniprot ID:
P40306
Molecular Weight:
28936.08 Da
References
  1. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25. [PubMed:17591945 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Comments
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Drug created on May 29, 2013 16:03 / Updated on December 03, 2016 02:46