U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C40H57N5O7
Molecular Weight 719.9114
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARFILZOMIB

SMILES

CC(C)C[C@@]([H])(C(=O)[C@@]1(C)CO1)N=C([C@]([H])(Cc2ccccc2)N=C([C@]([H])(CC(C)C)N=C([C@]([H])(CCc3ccccc3)N=C(CN4CCOCC4)O)O)O)O

InChI

InChIKey=BLMPQMFVWMYDKT-NZTKNTHTSA-N
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

HIDE SMILES / InChI

Molecular Formula C40H57N5O7
Molecular Weight 719.9114
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: http://www.ncbi.nlm.nih.gov/pubmed/?term=23386784; http://www.ncbi.nlm.nih.gov/pubmed/?term=17591945

Carfilzomib is an epoxomicin derivate with potential antineoplastic activity. Kyprolis (carfilzomib's trade name) is a proteasome inhibitor that is indicated for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy as a single agent or in combination with dexamethasone or with lenalidomide plus dexamethasone. Carfilzomib is made up of four modified peptides. It 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. Inhibition of proteasome-mediated proteolysis results in an accumulation of polyubiquinated proteins, which may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor growth.

CNS Activity

Curator's Comment:: Carfilzomib did not cross the blood–brain barrier

Originator

Curator's Comment:: Carfilzomib was discovered by Proteolix, Inc. company acquired by Onyx Pharmaceuticals, Inc in October 2009 which has been marketing carfilzomib under the trade name KYPROLIS

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
KYPROLIS

Approved Use

Indicated in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed multiple myeloma who have received one to three prior lines of therapy; as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy

Launch Date

1342742400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1389 ng/mL
56 mg/m² single, intravenous
dose: 56 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered: DEXAMETHASONE
CARFILZOMIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
563 ng × h/mL
56 mg/m² single, intravenous
dose: 56 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered: DEXAMETHASONE
CARFILZOMIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.34 h
56 mg/m² single, intravenous
dose: 56 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered: DEXAMETHASONE
CARFILZOMIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
CARFILZOMIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Disc. AE: Sepsis, Colon cancer...
Other AEs: Lymphopenia, Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Sepsis (serious, 1 patient)
Colon cancer (serious, 1 patient)
Other AEs:
Lymphopenia (grade 3-5, 75%)
Thrombocytopenia (grade 3-5, 50%)
Anaemia (grade 3-5, 50%)
Neutropenia (grade 3-5, 50%)
Pyrexia (grade 1-2, 75%)
Blood creatinine increased (grade 1-2, 50%)
White blood cell count increased (grade 1-2, 25%)
White blood cell count decreased (grade 3-5, 25%)
Nausea (grade 1-2, 50%)
Stomatitis (grade 1-2, 50%)
Neutrophil count increased (grade 1-2, 25%)
Nasopharyngitis (grade 1-2, 25%)
Vomiting (grade 1-2, 50%)
C-reactive protein increased (grade 1-2, 50%)
Hypophosphataemia (grade 1-2, 50%)
Hypertension (grade 1-2, 50%)
Malaise (grade 1-2, 25%)
Aspartate aminotransferase increased (grade 1-2, 25%)
Blood lactate dehydrogenase increased (grade 1-2, 25%)
Haematocrit decreased (grade 1-2, 25%)
Red blood cell count decreased (grade 1-2, 25%)
Weight gain (grade 1-2, 25%)
Sources:
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Disc. AE: Congestive heart failure, Cardiac arrest...
AEs leading to
discontinuation/dose reduction:
Congestive heart failure (2%)
Cardiac arrest (1%)
Dyspnea (1%)
Blood creatinine increased (1%)
Acute renal failure (1%)
Sources:
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Disc. AE: Pneumonia, Pyrexia...
AEs leading to
discontinuation/dose reduction:
Pneumonia (2%)
Pyrexia (1%)
Thrombocytopenia (1%)
Sources:
70 mg/m2 2 times / week multiple, intravenous
Highest studied dose
Dose: 70 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 70 mg/m2, 2 times / week
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
DLT: Adverse event...
Dose limiting toxicities:
Adverse event
Sources:
AEs

AEs

AESignificanceDosePopulation
Aspartate aminotransferase increased grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Blood lactate dehydrogenase increased grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Haematocrit decreased grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Malaise grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Nasopharyngitis grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Neutrophil count increased grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Red blood cell count decreased grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Weight gain grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
White blood cell count increased grade 1-2, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Blood creatinine increased grade 1-2, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
C-reactive protein increased grade 1-2, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Hypertension grade 1-2, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Hypophosphataemia grade 1-2, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Nausea grade 1-2, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Stomatitis grade 1-2, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Vomiting grade 1-2, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Pyrexia grade 1-2, 75%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
White blood cell count decreased grade 3-5, 25%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Anaemia grade 3-5, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Neutropenia grade 3-5, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Thrombocytopenia grade 3-5, 50%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Lymphopenia grade 3-5, 75%
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Colon cancer serious, 1 patient
Disc. AE
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Sepsis serious, 1 patient
Disc. AE
56 mg/m2 2 times / week multiple, intravenous
MTD
Dose: 56 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 56 mg/m2, 2 times / week
Sources:
unhealthy, 58 years (range:46–75 years)
Health Status: unhealthy
Age Group: 58 years (range:46–75 years)
Sex: M+F
Sources:
Acute renal failure 1%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Blood creatinine increased 1%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Cardiac arrest 1%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Dyspnea 1%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Congestive heart failure 2%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Pyrexia 1%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Thrombocytopenia 1%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Pneumonia 2%
Disc. AE
20 mg/m2 2 times / week steady, intravenous
Recommended
Dose: 20 mg/m2, 2 times / week
Route: intravenous
Route: steady
Dose: 20 mg/m2, 2 times / week
Sources:
unhealthy, 63.0 years (range: 37- 87 years)
Health Status: unhealthy
Age Group: 63.0 years (range: 37- 87 years)
Sex: M+F
Sources:
Adverse event DLT, Disc. AE
70 mg/m2 2 times / week multiple, intravenous
Highest studied dose
Dose: 70 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 70 mg/m2, 2 times / week
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
minor
yes (co-administration study)
Comment: carfilzomib inhibits digoxin by 25%
Page: 18
moderate [IC50 0.5 uM]
no (co-administration study)
Comment: carfilzomib did not affect the cmax and auc of midazolam
Page: 18
no
no
no
no
no
no
no
weak [IC50 3 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
no
no
no
no
no
no
no (co-administration study)
Comment: carfilzomib has no effect on midazolam
Page: 18
yes
yes (co-administration study)
Comment: ketoconazole decreased carfilzomib efflux ratio
Page: 18
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Epoxomicin, a new antitumor agent of microbial origin.
1992 Nov
Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma.
2007 Nov 1
Practical considerations for multiple myeloma: an overview of recent data and current options.
2008 Aug
Mechanisms of proteasome inhibitor action and resistance in cancer.
2008 Aug-Oct
The potential of proteasome inhibitors in cancer therapy.
2008 Jun
Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma.
2008 Jun 1
Gateways to clinical trials.
2008 Mar
The BH3-only mimetic ABT-737 synergizes the antineoplastic activity of proteasome inhibitors in lymphoid malignancies.
2008 Oct 1
Targeting the UPS as therapy in multiple myeloma.
2008 Oct 21
The development and pharmacology of proteasome inhibitors for the management and treatment of cancer.
2009
Novel therapies for relapsed myeloma.
2009
Gateways to clinical trials.
2009 Apr
Ubiquitin Drug Discovery & Diagnostics 2009 - First Annual Conference.
2009 Dec
Discovery of novel proteasome inhibitors using a high-content cell-based screening system.
2009 Dec 30
Clinical development of novel proteasome inhibitors for cancer treatment.
2009 Jul
New drugs in multiple myeloma and the significance of autologous stem cell transplants.
2009 Mar
Antiproliferative and proapoptotic effects of proteasome inhibitors and their combination with histone deacetylase inhibitors on leukemia cells.
2009 Mar
Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047).
2009 May 14
Gateways to clinical trials.
2009 Nov
Proteasome inhibitors in the treatment of multiple myeloma.
2009 Nov
Acquisition of a multidrug-resistant phenotype with a proteasome inhibitor in multiple myeloma.
2009 Nov
A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies.
2009 Nov 15
Future novel single agent and combination therapies.
2009 Nov-Dec
Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome.
2009 Oct 15
Relapsed multiple myeloma.
2010
State-of-the-Art Management of Complications of Myeloma and Its Treatment.
2010
Proteasome inhibitors: recent advances and new perspectives in medicinal chemistry.
2010
Bortezomib.
2010
Novel disease targets and management approaches for diffuse large B-cell lymphoma.
2010 Aug
New twists on proteasome inhibitors.
2010 Dec
Targeting histone deacetyalses in the treatment of B- and T-cell malignancies.
2010 Dec
Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70.
2010 Jan
Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies.
2010 Jul
Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy.
2010 Jun 15
The pan-HDAC inhibitor vorinostat potentiates the activity of the proteasome inhibitor carfilzomib in human DLBCL cells in vitro and in vivo.
2010 Jun 3
Characterization of a new series of non-covalent proteasome inhibitors with exquisite potency and selectivity for the 20S beta5-subunit.
2010 Sep 15
Proteasome inhibition and its therapeutic potential in multiple myeloma.
2010 Sep 28
A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation.
2011 Jun 19
Carfilzomib.
2013 Feb 7
Possible role of selective, irreversible, proteasome inhibitor (carfilzomib) in the treatment of rat hepatocellular carcinoma.
2014 May 25
Patents

Sample Use Guides

For monotherapy, administer Kyprolis intravenously as a 10-minute or 30-minute infusion depending on the regimen as described: for monotherapy using the 20/27 mg/m^2 regimen, administer Kyprolis intravenously as a 10-minute infusion. In Cycles 1 through 12, administer Kyprolis on two consecutive days, each week for three weeks followed by a 12-day rest period. Each 28-day period is considered one treatment cycle. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis. The recommended starting dose of Kyprolis is 20 mg/m^2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m^2 on Day 8 of Cycle 1. Treatment may continue until disease progression or unacceptable toxicity occurs.
Route of Administration: Intravenous
To determine whether JNK activation is important in mediating carfilzomib-induced apoptosis, RPMI 8226 cells were exposed to a pulse of 100 nM carfilzomib
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:31:25 UTC 2021
Edited
by admin
on Fri Jun 25 21:31:25 UTC 2021
Record UNII
72X6E3J5AR
Record Status Validated (UNII)
Record Version
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Name Type Language
CARFILZOMIB
DASH   INN   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
CARFILZOMIB [ORANGE BOOK]
Common Name English
PR-171
Code English
NSC-758252
Code English
L-PHENYLALANINAMIDE, (.ALPHA.S)-.ALPHA.-((4-MORPHOLINYLACETYL)AMINO)BENZENEBUTANOYL-L-LEUCYL-N-((1S)-3-METHYL-1-(((2R)-2-METHYLOXIRANYL)CARBONYL)BUTYL)-
Common Name English
(2S)-N-((1S)-1-BENZYL-2-(((1S)-3-METHYL-1-(((2R)-2-METHYLOXIRAN-2-YL)CARBONYL)BUTYL)AMINO)-2-OXOETHYL)-4-METHYL-2-(((2S)-2-((MORPHOLIN-4-YLACETYL)AMINO)-4-PHENYLBUTANOYL)AMINO)PENTANAMIDE
Common Name English
KYPROLIS
Brand Name English
CARFILZOMIB [WHO-DD]
Common Name English
CARFILZOMIB [MI]
Common Name English
CARFILZOMIB [USAN]
Common Name English
CARFILZOMIB [VANDF]
Common Name English
CARFILZOMIB [JAN]
Common Name English
CARFILZOMIB [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 795120
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
NDF-RT N0000175604
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
FDA ORPHAN DRUG 252507
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
WHO-VATC QL01XX45
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
EMA ASSESSMENT REPORTS KYPROLIS (AUTHORIZED: MULTIPLE MYELOMA)
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
EU-Orphan Drug EU/3/08/548
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
WHO-ATC L01XX45
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
NCI_THESAURUS C2160
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C52196
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
WIKIPEDIA
Carfilzomib
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
INN
8859
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
CAS
868540-17-4
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
FDA UNII
72X6E3J5AR
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
MESH
C524865
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
MERCK INDEX
M3107
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB08889
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
RXCUI
1302966
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY RxNorm
EVMPD
SUB32911
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
LACTMED
Carfilzomib
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
EPA CompTox
868540-17-4
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
DRUG CENTRAL
4483
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
IUPHAR
7420
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
ChEMBL
CHEMBL451887
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
PUBCHEM
11556711
Created by admin on Fri Jun 25 21:31:25 UTC 2021 , Edited by admin on Fri Jun 25 21:31:25 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
WEAK
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
IC50
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
MAJOR
PLASMA; URINE
METABOLITE INACTIVE -> PARENT
Cytochrome P450-mediated mechanisms played a minor role in overall carfilzomib metabolism
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC