Identification

Name
Carfilzomib
Accession Number
DB08889
Type
Small Molecule
Groups
Approved, Investigational
Description

Carfilzomib 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
Not Available
External IDs
PR-171
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KyprolisInjection, powder, lyophilized, for solution60 mg/30mLIntravenousOnyx Pharmaceuticals2012-07-20Not applicableUs
KyprolisInjection, powder, lyophilized, for solution10 mg/5mLIntravenousOnyx Pharmaceuticals2018-05-23Not applicableUs
KyprolisPowder, for solution60 mgIntravenousAmgen2016-02-11Not applicableCanada
KyprolisPowder, for solution30 mgIntravenousAmgen2017-02-06Not applicableCanada
KyprolisInjection, powder, lyophilized, for solution30 mg/15mLIntravenousOnyx Pharmaceuticals2016-07-15Not applicableUs
KyprolisPowder, for solution10 mgIntravenousAmgen2017-02-13Not applicableCanada
International/Other Brands
Kyprolis
Categories
UNII
72X6E3J5AR
CAS number
868540-17-4
Weight
Average: 719.9099
Monoisotopic: 719.425799203
Chemical Formula
C40H57N5O7
InChI Key
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[C@H](NC(=O)[C@H](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

Indication

Carfilzomib 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.

Associated Conditions
Pharmacodynamics

Intravenous 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 action

Carfilzomib 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.

TargetActionsOrganism
AProteasome subunit beta type-5
inhibitor
Human
AProteasome subunit beta type-8
inhibitor
Human
AProteasome subunit beta type-1
inhibitor
Human
AProteasome subunit beta type-9
inhibitor
Human
AProteasome subunit beta type-2
inhibitor
Human
AProteasome subunit beta type-10
inhibitor
Human
Absorption

Cmax, 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 binding

Over 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 elimination
Not Available
Half life

Following 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.

Toxicity

Most 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not 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
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Carfilzomib.Experimental
AmiodaroneThe serum concentration of Carfilzomib can be increased when it is combined with Amiodarone.Approved, Investigational
AmlodipineThe serum concentration of Carfilzomib can be increased when it is combined with Amlodipine.Approved
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Carfilzomib.Approved, Investigational, Withdrawn
ApalutamideThe serum concentration of Carfilzomib can be decreased when it is combined with Apalutamide.Approved, Investigational
Beclomethasone dipropionateThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Beclomethasone dipropionate.Approved, Investigational
Benzyl alcoholThe serum concentration of Carfilzomib can be increased when it is combined with Benzyl alcohol.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
BudesonideThe risk or severity of adverse effects can be increased when Budesonide is combined with Carfilzomib.Approved
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
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Carfilzomib.Approved, Investigational
CarvedilolThe serum concentration of Carfilzomib can be increased when it is combined with Carvedilol.Approved, Investigational
ClozapineThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Carfilzomib.Approved, Investigational
CyclosporineThe risk or severity of adverse effects can be increased when Cyclosporine is combined with Carfilzomib.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Carfilzomib.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Carfilzomib.Approved
DexamethasoneThe risk or severity of adverse effects can be increased when Dexamethasone is combined with Carfilzomib.Approved, Investigational, Vet Approved
DexniguldipineThe serum concentration of Carfilzomib can be increased when it is combined with Dexniguldipine.Experimental
DexverapamilThe serum concentration of Carfilzomib can be increased when it is combined with Dexverapamil.Experimental
DigitoxinDigitoxin may decrease the cardiotoxic activities of Carfilzomib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Carfilzomib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Carfilzomib.Approved
DiltiazemThe serum concentration of Carfilzomib can be increased when it is combined with Diltiazem.Approved, Investigational
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
EmopamilThe serum concentration of Carfilzomib can be increased when it is combined with Emopamil.Experimental
EverolimusThe risk or severity of adverse effects can be increased when Everolimus is combined with Carfilzomib.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
FluoxetineThe serum concentration of Carfilzomib can be increased when it is combined with Fluoxetine.Approved, Vet Approved
Fluticasone propionateThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Fluticasone propionate.Approved
FluvoxamineThe serum concentration of Carfilzomib can be increased when it is combined with Fluvoxamine.Approved, Investigational
GallopamilThe serum concentration of Carfilzomib can be increased when it is combined with Gallopamil.Investigational
GemcitabineThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Carfilzomib.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Carfilzomib.Experimental
GlyburideThe serum concentration of Carfilzomib can be increased when it is combined with Glyburide.Approved
GlycerinThe serum concentration of Carfilzomib can be increased when it is combined with Glycerin.Approved, Investigational
HydrocortisoneThe risk or severity of adverse effects can be increased when Hydrocortisone is combined with Carfilzomib.Approved, Vet Approved
Hydrocortisone acetateThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Hydrocortisone acetate.Approved, Vet Approved
Hydrocortisone butyrateThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Hydrocortisone butyrate.Approved, Vet Approved
IbuprofenThe serum concentration of Carfilzomib can be increased when it is combined with Ibuprofen.Approved
IrinotecanThe risk or severity of adverse effects can be increased when Irinotecan is combined with Carfilzomib.Approved, Investigational
IsavuconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Isavuconazole.Approved, Investigational
IsradipineThe serum concentration of Carfilzomib can be increased when it is combined with Isradipine.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Carfilzomib.Experimental
LidocaineThe serum concentration of Carfilzomib can be increased when it is combined with Lidocaine.Approved, Vet Approved
LipegfilgrastimCarfilzomib may increase the myelosuppressive activities of Lipegfilgrastim.Approved, Investigational
LomerizineThe serum concentration of Carfilzomib can be increased when it is combined with Lomerizine.Experimental
LoperamideThe serum concentration of Carfilzomib can be increased when it is combined with Loperamide.Approved
LoratadineThe serum concentration of Carfilzomib can be increased when it is combined with Loratadine.Approved, Investigational
LosartanThe serum concentration of Carfilzomib can be increased when it is combined with Losartan.Approved
LumacaftorThe serum concentration of Carfilzomib can be decreased when it is combined with Lumacaftor.Approved
MetamizoleThe risk or severity of myelosuppression can be increased when Metamizole is combined with Carfilzomib.Approved, Investigational, Withdrawn
MethimazoleThe risk or severity of adverse effects can be increased when Methimazole is combined with Carfilzomib.Approved
MethylprednisoloneThe risk or severity of adverse effects can be increased when Methylprednisolone is combined with Carfilzomib.Approved, Vet Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Carfilzomib.Experimental
MibefradilThe serum concentration of Carfilzomib can be increased when it is combined with Mibefradil.Investigational, Withdrawn
MiconazoleThe serum concentration of Carfilzomib can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
NicardipineThe serum concentration of Carfilzomib can be increased when it is combined with Nicardipine.Approved, Investigational
NiguldipineThe serum concentration of Carfilzomib can be increased when it is combined with Niguldipine.Experimental
NimodipineThe serum concentration of Carfilzomib can be increased when it is combined with Nimodipine.Approved, Investigational
NisoldipineThe serum concentration of Carfilzomib can be increased when it is combined with Nisoldipine.Approved
NitrendipineThe serum concentration of Carfilzomib can be increased when it is combined with Nitrendipine.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Carfilzomib.Experimental, Investigational
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
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Carfilzomib.Approved, Vet Approved
ParoxetineThe serum concentration of Carfilzomib can be increased when it is combined with Paroxetine.Approved, Investigational
PeruvosidePeruvoside may decrease the cardiotoxic activities of Carfilzomib.Experimental
PitolisantThe serum concentration of Carfilzomib can be decreased when it is combined with Pitolisant.Approved, Investigational
PrednisoloneThe risk or severity of adverse effects can be increased when Prednisolone is combined with Carfilzomib.Approved, Vet Approved
PromethazineThe serum concentration of Carfilzomib can be increased when it is combined with Promethazine.Approved, Investigational
PropafenoneThe serum concentration of Carfilzomib can be increased when it is combined with Propafenone.Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Carfilzomib.Experimental
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
RifampicinThe serum concentration of Carfilzomib can be increased when it is combined with Rifampicin.Approved
SulfasalazineThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Sulfasalazine.Approved
TetrandrineThe risk or severity of adverse effects can be increased when Carfilzomib is combined with Tetrandrine.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Carfilzomib.Approved, Investigational
VemurafenibThe serum concentration of Carfilzomib can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe serum concentration of Carfilzomib can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Carfilzomib can be increased when it is combined with Verapamil.Approved
ZidovudineThe risk or severity of adverse effects can be increased when Zidovudine is combined with Carfilzomib.Approved
Food Interactions
Not Available

References

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
KEGG Drug
D08880
PubChem Compound
11556711
PubChem Substance
175427135
ChemSpider
9731489
BindingDB
50277889
ChEBI
65347
ChEMBL
CHEMBL451887
PharmGKB
PA166165203
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carfilzomib
ATC Codes
L01XX45 — Carfilzomib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (310 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentMultiple Myeloma (MM)1
1Active Not RecruitingNot AvailableEnd-Stage Renal Disease (ESRD) / Relapsed Multiple Myeloma1
1Active Not RecruitingTreatmentMalignant Lymphomas1
1Active Not RecruitingTreatmentMultiple Myeloma (MM)4
1Active Not RecruitingTreatmentPlasma Cell Myeloma3
1Active Not RecruitingTreatmentRecurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Stage I Cutaneous T-cell Non-Hodgkin Lymphoma / Stage IA Mycosis Fungoides/Sezary Syndrome / Stage IB Mycosis Fungoides/Sezary Syndrome / Stage II Cutaneous T-cell Non-Hodgkin Lymphoma / Stage IIA Mycosis Fungoides/Sezary Syndrome / Stage IIB Mycosis Fungoides/Sezary Syndrome / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IIIA Mycosis Fungoides/Sezary Syndrome / Stage IIIB Mycosis Fungoides/Sezary Syndrome / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IVA Mycosis Fungoides/Sezary Syndrome / Stage IVB Mycosis Fungoides/Sezary Syndrome1
1CompletedNot AvailableHepatic Impairment / Malignancies, Hematologic / Tumors, Solid1
1CompletedTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult T-Cell Leukemia/Lymphoma1
1CompletedTreatmentAll / Blast Crisis / Leukemia Acute Myeloid Leukemia (AML) / Multiple Myeloma (MM) / Smith-Magenis Syndrome1
1CompletedTreatmentAmyloidosis / Systemic Light Chain Amyloidosis1
1CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia / Hematopoietic/Lymphoid Cancer / Leukemia, Prolymphocytic / Recurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia1
1CompletedTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL) / Peripheral T-Cell Lymphoma (PTCL)1
1CompletedTreatmentHodgkins Disease (HD) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Waldenström's Macroglobulinemia (WM)1
1CompletedTreatmentLeukemias1
1CompletedTreatmentMalignancies / Neoplasms1
1CompletedTreatmentMalignant Lymphomas1
1CompletedTreatmentMultiple Myeloma (MM)2
1CompletedTreatmentRelapsed Multiple Myeloma1
1Not Yet RecruitingTreatmentBreast Adenocarcinoma / Recurrent Breast Carcinoma / Recurrent Hodgkin Lymphoma / Recurrent Mycosis Fungoides / Recurrent Non-Hodgkin Lymphoma / Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Refractory Hodgkin Lymphoma / Refractory Nodal Marginal Zone Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory, advanced Mycosis fungoides / Refractory, primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Breast Cancer AJCC v6 and v71
1Not Yet RecruitingTreatmentRecurrent Plasma Cell Myeloma1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1RecruitingTreatmentAnemias / Hypercalcemia / Lytic Bone Lesion / Osteopenia / Pathologic fracture / Recurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
1RecruitingTreatmentContiguous Stage II Adult Lymphoblastic Lymphoma / Noncontiguous Stage II Adult Lymphoblastic Lymphoma / Stage I Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia1
1RecruitingTreatmentLeukemias / Pediatric Leukemia / Pediatric Solid Tumors1
1RecruitingTreatmentLeukemias / Refractory Solid Tumors / Relapsed Solid Tumors1
1RecruitingTreatmentMalignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentMultiple Myeloma (MM)1
1RecruitingTreatmentRefractory Multiple Myeloma1
1RecruitingTreatmentTransplants and Implants1
1SuspendedTreatmentHypercalcemia / Plasmacytoma / Recurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
1TerminatedTreatmentCancers1
1, 2Active Not RecruitingTreatmentAdvanced Malignancies / Cancer, Advanced / Metastatic Cancers / Tumors, Solid1
1, 2Active Not RecruitingTreatmentCancer of the Ovary / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancer Small Cell Lung Cancer (SCLC) / Malignant Lymphomas / Multiple Myeloma (MM) / Renal Cancers / Tumors, Solid1
1, 2Active Not RecruitingTreatmentDS Stage I Plasma Cell Myeloma / DS Stage II Plasma Cell Myeloma / DS Stage III Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
1, 2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD) / Malignancies, Hematologic / Relapses1
1, 2Active Not RecruitingTreatmentMalignant Lymphomas2
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)9
1, 2Active Not RecruitingTreatmentRelapsed or Refractory / Relapsed or Refractory B- / T-Cell Lymphomas1
1, 2CompletedTreatmentExtensive-Stage Small-Cell Lung Cancer1
1, 2CompletedTreatmentMultiple Myeloma (MM)2
1, 2CompletedTreatmentMultiple Myeloma (MM) / Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
1, 2CompletedTreatmentPlasma Cell Myeloma1
1, 2Not Yet RecruitingTreatmentAmyloidosis1
1, 2RecruitingTreatmentCD20 Positive / Contiguous Stage II Adult Diffuse Large Cell Lymphoma / Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Stage I Adult Diffuse Large Cell Lymphoma / Stage I Diffuse Large B-Cell Lymphoma / Stage II Diffuse Large B-Cell Lymphoma / Stage III Adult Diffuse Large Cell Lymphoma / Stage III Diffuse Large B-Cell Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Diffuse Large B-Cell Lymphoma1
1, 2RecruitingTreatmentContiguous Stage II Adult Diffuse Large Cell Lymphoma / Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma / Stage I Adult Diffuse Large Cell Lymphoma / Stage III Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma1
1, 2RecruitingTreatmentHodgkins Disease (HD) / Non-Hodgkin's Lymphoma (NHL)1
1, 2RecruitingTreatmentIrinotecan Sensitive Cancers / Non Small Cell Lung Carcinoma (NSCLC) / Small Cell Lung Carcinoma1
1, 2RecruitingTreatmentMultiple Myeloma (MM)5
1, 2RecruitingTreatmentMultiple Myeloma (MM) / Refractory Multiple Myeloma / Relapsed/Refractory Multiple Myeloma1
1, 2RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL)1
1, 2TerminatedTreatmentLeukemia, Plasma Cell / Multiple Myeloma (MM)1
1, 2WithdrawnTreatmentMultiple Myeloma (MM)1
2Active Not RecruitingTreatmentChronic Graft Versus Host Disease1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)8
2Active Not RecruitingTreatmentNeuroendocrine Cancer1
2Active Not RecruitingTreatmentPrior Bortezomib Therapy Acceptable / Waldenstroms1
2Active Not RecruitingTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2Active Not RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
2Active Not RecruitingTreatmentRenal Cancers1
2Active Not RecruitingTreatmentSmoldering Multiple Myeloma (SMM) / Smoldering Multiple Myeloma at High Risk of Progression to Symptomatic Multiple Myeloma1
2Active Not RecruitingTreatmentStage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
2CompletedTreatmentImpaired Renal Function / Multiple Myeloma (MM)1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMetastatic Castration Resistant Prostate Cancer1
2CompletedTreatmentMultiple Myeloma (MM)3
2CompletedTreatmentMultiple Myeloma (MM) / Tumors, Solid1
2CompletedTreatmentRefractory Multiple Myeloma / Relapse Multiple Myeloma1
2CompletedTreatmentWaldenström's Macroglobulinemia (WM)1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM)1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM) / Plasma Cell Myeloma1
2Not Yet RecruitingTreatmentPlasma Cell Myeloma1
2Not Yet RecruitingTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2Not Yet RecruitingTreatmentSmoldering Multiple Myeloma (SMM)1
2RecruitingTreatmentLung Transplant Rejection1
2RecruitingTreatmentMarginal Zone Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Waldenstrom Macroglobulinemia / Refractory Marginal Zone Lymphoma / Refractory Waldenstrom Macroglobulinemia / Waldenström's Macroglobulinemia (WM)1
2RecruitingTreatmentMultiple Myeloma (MM)12
2RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
2RecruitingTreatmentRelapsed and/or Refractory Multiple Myeloma1
2TerminatedTreatmentMultiple Myeloma (MM)1
2TerminatedTreatmentRefractory Multiple Myeloma1
2WithdrawnTreatmentMultiple Myeloma (MM)2
2WithdrawnTreatmentPlasma Cell Myeloma1
2WithdrawnTreatmentRefractory Multiple Myeloma / Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
3Active Not RecruitingTreatmentMultiple Myeloma (MM)2
3Active Not RecruitingTreatmentRelapsed Multiple Myeloma1
3Active Not RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
3Active Not RecruitingTreatmentRelapsed and Refractory Multiple Myeloma1
3CompletedTreatmentMultiple Myeloma (MM)3
3RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingTreatmentPlasma Cell Myeloma1
3RecruitingTreatmentPlasma Cell Myeloma / Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
4RecruitingTreatmentRelapsed and/or Refractory Multiple Myeloma1
Not AvailableApproved for MarketingNot AvailableMultiple Myeloma (MM)1
Not AvailableNo Longer AvailableNot AvailableMultiple Myeloma (MM)1
Not AvailableRecruitingNot AvailableMultiple Myeloma in Relapse1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous10 mg/5mL
Injection, powder, lyophilized, for solutionIntravenous30 mg/15mL
Injection, powder, lyophilized, for solutionIntravenous60 mg/30mL
Powder, for solutionIntravenous10 mg
Powder, for solutionIntravenous30 mg
Powder, for solutionIntravenous60 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7491704No2005-04-142025-04-14Us
US8129346No2006-12-252026-12-25Us
US8207127No2005-04-142025-04-14Us
US8207125No2005-04-142025-04-14Us
US7417042No2006-06-072026-06-07Us
US8207126No2005-04-142025-04-14Us
US7232818No2005-04-142025-04-14Us
US8207297No2005-04-142025-04-14Us
US7737112No2007-12-072027-12-07Us
US9493582No2013-02-272033-02-27Us
US9511109No2009-10-212029-10-21Us

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Phenylalanine and derivatives / Leucine and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Amphetamines and derivatives / N-acyl amines / Morpholines / Trialkylamines / Secondary carboxylic acid amides / Ketones
show 7 more
Substituents
Alpha-oligopeptide / Phenylalanine or derivatives / Leucine or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Amphetamine or derivatives / N-acyl-amine / Morpholine
show 27 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
epoxide, tetrapeptide, morpholines (CHEBI:65347)

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 ...
Gene Name
PSMB5
Uniprot ID
P28074
Uniprot Name
Proteasome subunit beta type-5
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 ...
Gene Name
PSMB8
Uniprot ID
P28062
Uniprot Name
Proteasome subunit beta type-8
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 ...
Gene Name
PSMB1
Uniprot ID
P20618
Uniprot Name
Proteasome subunit beta type-1
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 ...
Gene Name
PSMB9
Uniprot ID
P28065
Uniprot Name
Proteasome subunit beta type-9
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 ...
Gene Name
PSMB2
Uniprot ID
P49721
Uniprot Name
Proteasome subunit beta type-2
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 ...
Gene Name
PSMB10
Uniprot ID
P40306
Uniprot Name
Proteasome subunit beta type-10
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
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da

Drug created on May 29, 2013 16:03 / Updated on August 15, 2018 09:55