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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
Kyprolisinjection, powder, lyophilized, for solution60 mg/30mLintravenousOnyx Pharmaceuticals, Inc.2012-07-20Not applicableUs
Kyprolispowder for solution60 mgintravenousAmgen Canada Inc2016-02-11Not applicableCanada
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 KeyInChIKey=BLMPQMFVWMYDKT-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
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
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.
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.
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
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 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
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
Interactions
Drug Interactions
Drug
AcetaminophenThe serum concentration of Carfilzomib can be increased when it is combined with Acetaminophen.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Carfilzomib.
AfatinibThe serum concentration of Carfilzomib can be increased when it is combined with Afatinib.
AlbendazoleThe serum concentration of Carfilzomib can be increased when it is combined with Albendazole.
AldosteroneThe serum concentration of Carfilzomib can be decreased when it is combined with Aldosterone.
AlectinibThe serum concentration of Carfilzomib can be increased when it is combined with Alectinib.
AlfentanilThe serum concentration of Carfilzomib can be increased when it is combined with Alfentanil.
AmantadineThe serum concentration of Carfilzomib can be increased when it is combined with Amantadine.
Aminohippuric acidThe serum concentration of Carfilzomib can be increased when it is combined with Aminohippuric acid.
AmiodaroneThe serum concentration of Carfilzomib can be decreased when it is combined with Amiodarone.
AmitriptylineThe serum concentration of Carfilzomib can be increased when it is combined with Amitriptyline.
AmlodipineThe serum concentration of Carfilzomib can be increased when it is combined with Amlodipine.
AmprenavirThe serum concentration of Carfilzomib can be decreased when it is combined with Amprenavir.
AmsacrineThe serum concentration of Carfilzomib can be increased when it is combined with Amsacrine.
AstemizoleThe serum concentration of Carfilzomib can be increased when it is combined with Astemizole.
AtazanavirThe serum concentration of Carfilzomib can be increased when it is combined with Atazanavir.
AtenololThe serum concentration of Carfilzomib can be increased when it is combined with Atenolol.
AtorvastatinThe serum concentration of Carfilzomib can be increased when it is combined with Atorvastatin.
AzelastineThe serum concentration of Carfilzomib can be increased when it is combined with Azelastine.
AzithromycinThe serum concentration of Carfilzomib can be increased when it is combined with Azithromycin.
BenzocaineThe serum concentration of Carfilzomib can be increased when it is combined with Benzocaine.
BepridilThe serum concentration of Carfilzomib can be increased when it is combined with Bepridil.
BevacizumabBevacizumab may increase the cardiotoxic activities of Carfilzomib.
BiperidenThe serum concentration of Carfilzomib can be increased when it is combined with Biperiden.
BosutinibThe serum concentration of Carfilzomib can be increased when it is combined with Bosutinib.
BromocriptineThe serum concentration of Carfilzomib can be increased when it is combined with Bromocriptine.
BuprenorphineThe serum concentration of Carfilzomib can be increased when it is combined with Buprenorphine.
BuspironeThe serum concentration of Carfilzomib can be increased when it is combined with Buspirone.
CabazitaxelThe serum concentration of Carfilzomib can be increased when it is combined with Cabazitaxel.
CaffeineThe serum concentration of Carfilzomib can be increased when it is combined with Caffeine.
CanagliflozinThe serum concentration of Carfilzomib can be increased when it is combined with Canagliflozin.
CandesartanThe serum concentration of Carfilzomib can be increased when it is combined with Candesartan.
CaptoprilThe serum concentration of Carfilzomib can be increased when it is combined with Captopril.
CarbamazepineThe serum concentration of Carfilzomib can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of Carfilzomib can be increased when it is combined with Carvedilol.
CaspofunginThe serum concentration of Carfilzomib can be increased when it is combined with Caspofungin.
ChloroquineThe serum concentration of Carfilzomib can be increased when it is combined with Chloroquine.
ChlorpromazineThe serum concentration of Carfilzomib can be increased when it is combined with Chlorpromazine.
ChlorpropamideThe serum concentration of Carfilzomib can be increased when it is combined with Chlorpropamide.
ChlorprothixeneThe serum concentration of Carfilzomib can be increased when it is combined with Chlorprothixene.
CholesterolThe serum concentration of Carfilzomib can be increased when it is combined with Cholesterol.
Cholic AcidThe serum concentration of Carfilzomib can be decreased when it is combined with Cholic Acid.
CilazaprilThe serum concentration of Carfilzomib can be increased when it is combined with Cilazapril.
CimetidineThe serum concentration of Carfilzomib can be decreased when it is combined with Cimetidine.
CiprofloxacinThe serum concentration of Carfilzomib can be increased when it is combined with Ciprofloxacin.
CitalopramThe serum concentration of Carfilzomib can be increased when it is combined with Citalopram.
ClarithromycinThe serum concentration of Carfilzomib can be increased when it is combined with Clarithromycin.
ClofazimineThe serum concentration of Carfilzomib can be increased when it is combined with Clofazimine.
ClomipramineThe serum concentration of Carfilzomib can be increased when it is combined with Clomipramine.
ClotrimazoleThe serum concentration of Carfilzomib can be decreased when it is combined with Clotrimazole.
ClozapineThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Clozapine.
CobicistatThe serum concentration of Carfilzomib can be increased when it is combined with Cobicistat.
ColchicineThe serum concentration of Carfilzomib can be increased when it is combined with Colchicine.
ColforsinThe serum concentration of Carfilzomib can be increased when it is combined with Colforsin.
CrizotinibThe serum concentration of Carfilzomib can be increased when it is combined with Crizotinib.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Carfilzomib.
CyclosporineThe serum concentration of Carfilzomib can be decreased when it is combined with Cyclosporine.
DaclatasvirThe serum concentration of Carfilzomib can be increased when it is combined with Daclatasvir.
DactinomycinThe serum concentration of Carfilzomib can be increased when it is combined with Dactinomycin.
DasatinibThe serum concentration of Carfilzomib can be increased when it is combined with Dasatinib.
DaunorubicinThe serum concentration of Carfilzomib can be decreased when it is combined with Daunorubicin.
DesipramineThe serum concentration of Carfilzomib can be increased when it is combined with Desipramine.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Carfilzomib.
DesloratadineThe serum concentration of Carfilzomib can be increased when it is combined with Desloratadine.
DexamethasoneThe serum concentration of Carfilzomib can be decreased when it is combined with Dexamethasone.
DextromethorphanThe serum concentration of Carfilzomib can be increased when it is combined with Dextromethorphan.
DiclofenacThe serum concentration of Carfilzomib can be increased when it is combined with Diclofenac.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Carfilzomib.
DigoxinDigoxin may decrease the cardiotoxic activities of Carfilzomib.
DihydroergotamineThe serum concentration of Carfilzomib can be increased when it is combined with Dihydroergotamine.
DiltiazemThe serum concentration of Carfilzomib can be increased when it is combined with Diltiazem.
DipyridamoleThe serum concentration of Carfilzomib can be increased when it is combined with Dipyridamole.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Carfilzomib.
DoxazosinThe serum concentration of Carfilzomib can be increased when it is combined with Doxazosin.
DoxepinThe serum concentration of Carfilzomib can be increased when it is combined with Doxepin.
DoxorubicinThe serum concentration of Carfilzomib can be decreased when it is combined with Doxorubicin.
DronabinolThe serum concentration of Carfilzomib can be increased when it is combined with Dronabinol.
DronedaroneThe serum concentration of Carfilzomib can be increased when it is combined with Dronedarone.
ElbasvirThe serum concentration of Carfilzomib can be increased when it is combined with Elbasvir.
EnalaprilThe serum concentration of Carfilzomib can be increased when it is combined with Enalapril.
EnzalutamideThe serum concentration of Carfilzomib can be increased when it is combined with Enzalutamide.
ErgonovineThe serum concentration of Carfilzomib can be increased when it is combined with Ergonovine.
ErgotamineThe serum concentration of Carfilzomib can be increased when it is combined with Ergotamine.
ErythromycinThe serum concentration of Carfilzomib can be decreased when it is combined with Erythromycin.
EstramustineThe serum concentration of Carfilzomib can be increased when it is combined with Estramustine.
EstriolThe serum concentration of Carfilzomib can be decreased when it is combined with Estriol.
EstroneThe serum concentration of Carfilzomib can be decreased when it is combined with Estrone.
EtoposideThe serum concentration of Carfilzomib can be increased when it is combined with Etoposide.
EtravirineThe serum concentration of Carfilzomib can be increased when it is combined with Etravirine.
FelodipineThe serum concentration of Carfilzomib can be increased when it is combined with Felodipine.
FentanylThe serum concentration of Carfilzomib can be increased when it is combined with Fentanyl.
FexofenadineThe serum concentration of Carfilzomib can be increased when it is combined with Fexofenadine.
FidaxomicinThe serum concentration of Carfilzomib can be increased when it is combined with Fidaxomicin.
FluconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Fluconazole.
FluoxetineThe serum concentration of Carfilzomib can be increased when it is combined with Fluoxetine.
FlupentixolThe serum concentration of Carfilzomib can be increased when it is combined with Flupentixol.
FluphenazineThe serum concentration of Carfilzomib can be increased when it is combined with Fluphenazine.
FlurazepamThe serum concentration of Carfilzomib can be increased when it is combined with Flurazepam.
FluvoxamineThe serum concentration of Carfilzomib can be increased when it is combined with Fluvoxamine.
GefitinibThe serum concentration of Carfilzomib can be increased when it is combined with Gefitinib.
GenisteinThe serum concentration of Carfilzomib can be increased when it is combined with Genistein.
GlyburideThe serum concentration of Carfilzomib can be increased when it is combined with Glyburide.
GlycerolThe serum concentration of Carfilzomib can be increased when it is combined with Glycerol.
Gramicidin DThe serum concentration of Carfilzomib can be increased when it is combined with Gramicidin D.
GrepafloxacinThe serum concentration of Carfilzomib can be increased when it is combined with Grepafloxacin.
HaloperidolThe serum concentration of Carfilzomib can be increased when it is combined with Haloperidol.
HydrocortisoneThe serum concentration of Carfilzomib can be increased when it is combined with Hydrocortisone.
IdelalisibThe serum concentration of Carfilzomib can be increased when it is combined with Idelalisib.
ImatinibThe serum concentration of Carfilzomib can be increased when it is combined with Imatinib.
ImipramineThe serum concentration of Carfilzomib can be increased when it is combined with Imipramine.
IndinavirThe serum concentration of Carfilzomib can be decreased when it is combined with Indinavir.
IndomethacinThe serum concentration of Carfilzomib can be increased when it is combined with Indomethacin.
IsavuconazoniumThe serum concentration of Carfilzomib can be increased when it is combined with Isavuconazonium.
ItraconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Carfilzomib can be increased when it is combined with Ivacaftor.
IvermectinThe serum concentration of Carfilzomib can be increased when it is combined with Ivermectin.
KetamineThe serum concentration of Carfilzomib can be increased when it is combined with Ketamine.
KetoconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Ketoconazole.
LansoprazoleThe serum concentration of Carfilzomib can be increased when it is combined with Lansoprazole.
LapatinibThe serum concentration of Carfilzomib can be increased when it is combined with Lapatinib.
LevofloxacinThe serum concentration of Carfilzomib can be increased when it is combined with Levofloxacin.
LevothyroxineThe serum concentration of Carfilzomib can be decreased when it is combined with Levothyroxine.
LidocaineThe serum concentration of Carfilzomib can be increased when it is combined with Lidocaine.
LiothyronineThe serum concentration of Carfilzomib can be decreased when it is combined with Liothyronine.
LiotrixThe serum concentration of Carfilzomib can be decreased when it is combined with Liotrix.
LisinoprilThe serum concentration of Carfilzomib can be increased when it is combined with Lisinopril.
LomitapideThe serum concentration of Carfilzomib can be increased when it is combined with Lomitapide.
LoperamideThe serum concentration of Carfilzomib can be increased when it is combined with Loperamide.
LopinavirThe serum concentration of Carfilzomib can be increased when it is combined with Lopinavir.
LoratadineThe serum concentration of Carfilzomib can be increased when it is combined with Loratadine.
LosartanThe serum concentration of Carfilzomib can be increased when it is combined with Losartan.
LovastatinThe serum concentration of Carfilzomib can be increased when it is combined with Lovastatin.
LumacaftorThe serum concentration of Carfilzomib can be decreased when it is combined with Lumacaftor.
MaprotilineThe serum concentration of Carfilzomib can be increased when it is combined with Maprotiline.
MebendazoleThe serum concentration of Carfilzomib can be increased when it is combined with Mebendazole.
MefloquineThe serum concentration of Carfilzomib can be increased when it is combined with Mefloquine.
Megestrol acetateThe serum concentration of Carfilzomib can be increased when it is combined with Megestrol acetate.
MeprobamateThe serum concentration of Carfilzomib can be increased when it is combined with Meprobamate.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Carfilzomib.
MethadoneThe serum concentration of Carfilzomib can be increased when it is combined with Methadone.
MetoprololThe serum concentration of Carfilzomib can be increased when it is combined with Metoprolol.
MibefradilThe serum concentration of Carfilzomib can be increased when it is combined with Mibefradil.
MiconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Miconazole.
MidazolamThe serum concentration of Carfilzomib can be decreased when it is combined with Midazolam.
MifepristoneThe serum concentration of Carfilzomib can be decreased when it is combined with Mifepristone.
MitomycinThe serum concentration of Carfilzomib can be increased when it is combined with Mitomycin.
MitoxantroneThe serum concentration of Carfilzomib can be decreased when it is combined with Mitoxantrone.
MorphineThe serum concentration of Carfilzomib can be increased when it is combined with Morphine.
NaltrexoneThe serum concentration of Carfilzomib can be increased when it is combined with Naltrexone.
NaringeninThe serum concentration of Carfilzomib can be increased when it is combined with Naringenin.
NefazodoneThe serum concentration of Carfilzomib can be decreased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Carfilzomib can be decreased when it is combined with Nelfinavir.
NeostigmineThe serum concentration of Carfilzomib can be increased when it is combined with Neostigmine.
NicardipineThe serum concentration of Carfilzomib can be increased when it is combined with Nicardipine.
NifedipineThe serum concentration of Carfilzomib can be decreased when it is combined with Nifedipine.
NilotinibThe serum concentration of Carfilzomib can be increased when it is combined with Nilotinib.
NisoldipineThe serum concentration of Carfilzomib can be increased when it is combined with Nisoldipine.
NitrazepamThe serum concentration of Carfilzomib can be increased when it is combined with Nitrazepam.
NitrendipineThe serum concentration of Carfilzomib can be increased when it is combined with Nitrendipine.
NorethisteroneThe serum concentration of Carfilzomib can be decreased when it is combined with Norethisterone.
OmeprazoleThe serum concentration of Carfilzomib can be increased when it is combined with Omeprazole.
OuabainOuabain may decrease the cardiotoxic activities of Carfilzomib.
P-NitrophenolThe serum concentration of Carfilzomib can be increased when it is combined with P-Nitrophenol.
PaclitaxelThe serum concentration of Carfilzomib can be increased when it is combined with Paclitaxel.
Palmitic AcidThe serum concentration of Carfilzomib can be increased when it is combined with Palmitic Acid.
PantoprazoleThe serum concentration of Carfilzomib can be increased when it is combined with Pantoprazole.
ParoxetineThe serum concentration of Carfilzomib can be increased when it is combined with Paroxetine.
PerindoprilThe serum concentration of Carfilzomib can be increased when it is combined with Perindopril.
PhenobarbitalThe serum concentration of Carfilzomib can be decreased when it is combined with Phenobarbital.
PimozideThe serum concentration of Carfilzomib can be increased when it is combined with Pimozide.
Platelet Activating FactorThe serum concentration of Carfilzomib can be decreased when it is combined with Platelet Activating Factor.
PonatinibThe serum concentration of Carfilzomib can be increased when it is combined with Ponatinib.
PosaconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Posaconazole.
PravastatinThe serum concentration of Carfilzomib can be increased when it is combined with Pravastatin.
PrazosinThe serum concentration of Carfilzomib can be increased when it is combined with Prazosin.
PrednisoneThe serum concentration of Carfilzomib can be increased when it is combined with Prednisone.
ProbenecidThe serum concentration of Carfilzomib can be increased when it is combined with Probenecid.
ProgesteroneThe serum concentration of Carfilzomib can be decreased when it is combined with Progesterone.
PromethazineThe serum concentration of Carfilzomib can be increased when it is combined with Promethazine.
PropafenoneThe serum concentration of Carfilzomib can be increased when it is combined with Propafenone.
PropranololThe serum concentration of Carfilzomib can be increased when it is combined with Propranolol.
ProtriptylineThe serum concentration of Carfilzomib can be increased when it is combined with Protriptyline.
QuercetinThe serum concentration of Carfilzomib can be increased when it is combined with Quercetin.
QuinacrineThe serum concentration of Carfilzomib can be increased when it is combined with Quinacrine.
QuinidineThe serum concentration of Carfilzomib can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Carfilzomib can be increased when it is combined with Quinine.
RanitidineThe serum concentration of Carfilzomib can be increased when it is combined with Ranitidine.
RanolazineThe serum concentration of Carfilzomib can be increased when it is combined with Ranolazine.
ReboxetineThe serum concentration of Carfilzomib can be increased when it is combined with Reboxetine.
RegorafenibThe serum concentration of Carfilzomib can be increased when it is combined with Regorafenib.
ReserpineThe serum concentration of Carfilzomib can be decreased when it is combined with Reserpine.
RifampicinThe serum concentration of Carfilzomib can be decreased when it is combined with Rifampicin.
RilpivirineThe serum concentration of Carfilzomib can be increased when it is combined with Rilpivirine.
RitonavirThe serum concentration of Carfilzomib can be decreased when it is combined with Ritonavir.
RolapitantThe serum concentration of Carfilzomib can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Carfilzomib can be decreased when it is combined with Saquinavir.
ScopolamineThe serum concentration of Carfilzomib can be increased when it is combined with Scopolamine.
SelegilineThe serum concentration of Carfilzomib can be increased when it is combined with Selegiline.
SertralineThe serum concentration of Carfilzomib can be increased when it is combined with Sertraline.
SimeprevirThe serum concentration of Carfilzomib can be increased when it is combined with Simeprevir.
SimvastatinThe serum concentration of Carfilzomib can be increased when it is combined with Simvastatin.
SirolimusThe serum concentration of Carfilzomib can be decreased when it is combined with Sirolimus.
SorafenibThe serum concentration of Carfilzomib can be increased when it is combined with Sorafenib.
SpironolactoneThe serum concentration of Carfilzomib can be increased when it is combined with Spironolactone.
St. John's WortThe serum concentration of Carfilzomib can be decreased when it is combined with St. John's Wort.
StaurosporineThe serum concentration of Carfilzomib can be increased when it is combined with Staurosporine.
StreptozocinThe serum concentration of Carfilzomib can be decreased when it is combined with Streptozocin.
SulfinpyrazoneThe serum concentration of Carfilzomib can be increased when it is combined with Sulfinpyrazone.
SumatriptanThe serum concentration of Carfilzomib can be increased when it is combined with Sumatriptan.
SunitinibThe serum concentration of Carfilzomib can be increased when it is combined with Sunitinib.
TacrineThe serum concentration of Carfilzomib can be increased when it is combined with Tacrine.
TacrolimusThe serum concentration of Carfilzomib can be decreased when it is combined with Tacrolimus.
TamoxifenThe serum concentration of Carfilzomib can be decreased when it is combined with Tamoxifen.
Taurocholic AcidThe serum concentration of Carfilzomib can be increased when it is combined with Taurocholic Acid.
TelmisartanThe serum concentration of Carfilzomib can be increased when it is combined with Telmisartan.
TemsirolimusThe serum concentration of Carfilzomib can be increased when it is combined with Temsirolimus.
TerazosinThe serum concentration of Carfilzomib can be increased when it is combined with Terazosin.
TerfenadineThe serum concentration of Carfilzomib can be increased when it is combined with Terfenadine.
TesmilifeneThe serum concentration of Carfilzomib can be decreased when it is combined with Tesmilifene.
TestosteroneThe serum concentration of Carfilzomib can be increased when it is combined with Testosterone.
TicagrelorThe serum concentration of Carfilzomib can be increased when it is combined with Ticagrelor.
TolvaptanThe serum concentration of Carfilzomib can be increased when it is combined with Tolvaptan.
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Carfilzomib.
TrazodoneThe serum concentration of Carfilzomib can be decreased when it is combined with Trazodone.
TrifluoperazineThe serum concentration of Carfilzomib can be increased when it is combined with Trifluoperazine.
TriflupromazineThe serum concentration of Carfilzomib can be increased when it is combined with Triflupromazine.
TrimethoprimThe serum concentration of Carfilzomib can be decreased when it is combined with Trimethoprim.
TrimipramineThe serum concentration of Carfilzomib can be increased when it is combined with Trimipramine.
TroleandomycinThe serum concentration of Carfilzomib can be increased when it is combined with Troleandomycin.
VenlafaxineThe serum concentration of Carfilzomib can be increased when it is combined with Venlafaxine.
VerapamilThe serum concentration of Carfilzomib can be decreased when it is combined with Verapamil.
VinblastineThe serum concentration of Carfilzomib can be decreased when it is combined with Vinblastine.
VincristineThe serum concentration of Carfilzomib can be decreased when it is combined with Vincristine.
VinorelbineThe serum concentration of Carfilzomib can be increased when it is combined with Vinorelbine.
ZimelidineThe serum concentration of Carfilzomib can be increased when it is combined with Zimelidine.
Food InteractionsNot Available

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 September 30, 2016 02:27