| 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
| Molecular Formula | C40H57N5O7 |
| Molecular Weight | 719.9099 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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
Originator
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
PubMed
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
