| Stereochemistry | ABSOLUTE |
| Molecular Formula | C15H20ClNO4 |
| Molecular Weight | 313.777 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@@]12OC(=O)[C@@]1(NC(=O)[C@@H]2CCCl)[C@@H](O)[C@H]3CCCC=C3
InChI
InChIKey=NGWSFRIPKNWYAO-SHTIJGAHSA-N
InChI=1S/C15H20ClNO4/c1-14-10(7-8-16)12(19)17-15(14,13(20)21-14)11(18)9-5-3-2-4-6-9/h3,5,9-11,18H,2,4,6-8H2,1H3,(H,17,19)/t9-,10+,11+,14+,15+/m1/s1
Marizomib is a natural beta-lactone produced by the marine bacterium Salinispora tropica. Marizomib has a broad inhibition profile for the 20S proteasome and has been shown to inhibit the CT-L (beta5) CT-T-laspase-like (C-L, beta1) and trypsin-like (T-L, beta2) activities of the 20S proteasome. The drug is being tested in phase II clinical trials for the treatment of Multiple Myeloma and Malignant Glioma and in phase I in patients with Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma
CNS Activity
Originator
Approval Year
Doses
AEs
Sourcing
PubMed
Sample Use Guides
Patients with Multiple Myeloma receive marizomib at a dose of 0.5 mg/m2 as an intravenous infusion over 2 hours on Days 1, 4, 8, and 11 in each 21-day cycle. Patients with Malignant Glioma received marizomib at a dose of 0.8 mg/m2 as a 10-minute, IV infusion on Days 1, 8, and 15 of every 28-day cycle. Patients with Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma received marizomib as an intravenous injection over 1 to 10 minutes at doses ranging from 0.15 to 0.7 mg/m2 on Days 1, 8, and 15 of each 28-day Cycle in combination with oral vorinostat (300 mg).
Route of Administration:
Intravenous
PC-3 cells were plated in 96-well flat-bottomed plates and allowed to attach for 24 h at 37 degrees Celsius. The RPMI 8226 cells were plated in 96-well flat-bottomed plates on the day of testing. Serially
diluted marizomib (2 pM–20 uM) was added to the cells and incubated for 48 h. IC50 values were 10 nM and 35 nM for RPMI 8226 and PC-3 cells, respectively.
ACTIVE MOIETY
