Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C40H57N5O7 |
| Molecular Weight | 719.9099 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN2CCOCC2)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]4(C)CO4
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
DescriptionCurator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/?term=23386784; http://www.ncbi.nlm.nih.gov/pubmed/?term=17591945
Curator's Comment: description was created based on several sources, including
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2364701 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Secondary | KYPROLIS Approved UseIndicated 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 Date2012 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1389 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28424963 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
563 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28424963 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.34 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28424963 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3% |
CARFILZOMIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 Sources: |
Disc. AE: Sepsis, Colon cancer... Other AEs: Lymphopenia, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Sepsis (serious, 1 patient) Other AEs:Colon cancer (serious, 1 patient) Lymphopenia (grade 3-5, 75%) Sources: 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%) |
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) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 Sources: |
Disc. AE: Congestive heart failure, Cardiac arrest... AEs leading to discontinuation/dose reduction: Congestive heart failure (2%) Sources: Cardiac arrest (1%) Dyspnea (1%) Blood creatinine increased (1%) Acute renal failure (1%) |
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: Page: p. 51 |
unhealthy, 63.0 years (range: 37- 87 years) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 Sources: Page: p. 51 |
Disc. AE: Pneumonia, Pyrexia... AEs leading to discontinuation/dose reduction: Pneumonia (2%) Sources: Page: p. 51Pyrexia (1%) Thrombocytopenia (1%) |
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 n = 2 Health Status: unhealthy Condition: multiple myeloma Age Group: adult Population Size: 2 Sources: |
DLT: Adverse event... |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 4 Health Status: unhealthy Condition: relapsed or refractory multiple myeloma Age Group: 58 years (range:46–75 years) Sex: M+F Population Size: 4 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) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 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) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 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) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 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) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 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) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 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: Page: p. 51 |
unhealthy, 63.0 years (range: 37- 87 years) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 Sources: Page: p. 51 |
| 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: Page: p. 51 |
unhealthy, 63.0 years (range: 37- 87 years) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 Sources: Page: p. 51 |
| 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: Page: p. 51 |
unhealthy, 63.0 years (range: 37- 87 years) n = 526 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 63.0 years (range: 37- 87 years) Sex: M+F Population Size: 526 Sources: Page: p. 51 |
| 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 n = 2 Health Status: unhealthy Condition: multiple myeloma Age Group: adult Population Size: 2 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| minor | yes (co-administration study) Comment: carfilzomib inhibits digoxin by 25% Page: 18.0 |
|||
| moderate [IC50 0.5 uM] | no (co-administration study) Comment: carfilzomib did not affect the cmax and auc of midazolam Page: 18.0 |
|||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| weak [IC50 3 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| major | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | no (co-administration study) Comment: carfilzomib has no effect on midazolam Page: 18.0 |
|||
| yes | yes (co-administration study) Comment: ketoconazole decreased carfilzomib efflux ratio Page: 18.0 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
|
| Gateways to clinical trials. | 2009 Apr |
|
| Ubiquitin Drug Discovery & Diagnostics 2009 - First Annual Conference. | 2009 Dec |
|
| Antiproliferative and proapoptotic effects of proteasome inhibitors and their combination with histone deacetylase inhibitors on leukemia cells. | 2009 Mar |
|
| 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 |
|
| Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. | 2009 Oct 15 |
|
| Relapsed multiple myeloma. | 2010 |
|
| New twists on proteasome inhibitors. | 2010 Dec |
|
| Targeting histone deacetyalses in the treatment of B- and T-cell malignancies. | 2010 Dec |
|
| Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies. | 2010 Jul |
|
| Proteasome inhibition and its therapeutic potential in multiple myeloma. | 2010 Sep 28 |
|
| 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.
For the combination regimen with lenalidomide and dexamethasone, administer Kyprolis intravenously as a 10-minute infusion 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. 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. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis. Discontinue Kyprolis after Cycle 18. Lenalidomide 25 mg is taken orally on Days 1–21 and dexamethasone 40 mg by mouth or intravenously on days 1, 8, 15, and 22 of the 28-day cycles. Continue treatment until disease progression or unacceptable toxicity occurs.
Route of Administration:
Intravenous
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FDA ORPHAN DRUG |
795120
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
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NDF-RT |
N0000175604
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
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FDA ORPHAN DRUG |
252507
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
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WHO-VATC |
QL01XX45
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
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||
|
EMA ASSESSMENT REPORTS |
KYPROLIS (AUTHORIZED: MULTIPLE MYELOMA)
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
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EU-Orphan Drug |
EU/3/08/548
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
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WHO-ATC |
L01XX45
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
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NCI_THESAURUS |
C2160
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
C52196
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
Carfilzomib
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
65347
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
8859
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
868540-17-4
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
72X6E3J5AR
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
72X6E3J5AR
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
C524865
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
SS-92
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
758252
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
m3107
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | Merck Index | ||
|
DB08889
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
1302966
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | RxNorm | ||
|
100000126282
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
SUB32911
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
Carfilzomib
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
DTXSID4048690
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
4483
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
7420
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
CHEMBL451887
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY | |||
|
11556711
Created by
admin on Fri Dec 15 15:54:47 GMT 2023 , Edited by admin on Fri Dec 15 15:54:47 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE INACTIVE (PARENT)
