Marizomib
DCTPepD ID DCTPepD0092
Active Ingredients Marizomib
Description A naturally-occurring salinosporamide, isolated from the marine actinomycete Salinospora tropica, with potential antineoplastic activity. Marizomib irreversibly binds to and inhibits the 20S catalytic core subunit of the proteasome by covalently modifying its active site threonine residues; inhibition of ubiquitin-proteasome mediated proteolysis results in an accumulation of poly-ubiquitinated proteins, which may result in the disruption of cellular processes, cell cycle arrest, the induction of apoptosis, and the inhibition of tumor growth and angiogenesis. This agent more may more potent and selective than the proteasome inhibitor bortezomib.
Synonyms (1R,4R,5S)-4-(2-chloroethyl)-1-{(S)-[(1S)-cyclohex-2-en-1-yl]hydroxymethyl}-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione; Marizomib; ML 858; NPI-0052; Salinosporamide A; Salinosporin A
Disease Melanoma, Lymphoma, Glioblastoma, Malignant Glioma
Classification
Amino acid and derivative
Structure Information
Molecular Formula C15H20ClNO4
Molecular Weight 313.77
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name (1R,4R,5S)-4-(2-chloroethyl)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione
InChI 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
InChI_Key NGWSFRIPKNWYAO-SHTIJGAHSA-N
SMILES O=C([C@H](CCCl)[C@]1(C)O2)N[C@@]1([C@H]([C@@H]3C=CCCC3)O)C2=O
External Codes
PubChem CID 11347535
DrugBank Accession Number DB11762
NCI Thesaurus Code C64634
UNII 703P9YDP7F GSRS
CAS 437742-34-2
Drug approval
Drug indication
Marizomib has been used in trials studying the treatment of Cancer, Melanoma, Lymphoma, Glioblastoma, and Malignant Glioma, among others.
The drug is not approved.
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT04341311 | Phase 1 Trial of Marizomib Alone and in Combination With Panobinostat for Children With Diffuse Intrinsic Pontine Glioma | Diffuse Intrinsic Pontine Glioma; Pediatric Brainstem Glioma; Pediatric Brainstem Gliosarcoma, Recurrent; Pediatric Cancer; Pediatric Brain Tumor; Diffuse Glioma | Phase 1 | Treatment |
| NCT02103335 | A Phase 1, Multicenter, Open-label, Dose-Escalation Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma | Multiple Myeloma in Relapse; Refractory Multiple Myeloma; Multiple Myeloma | Phase 1 | Treatment |
| NCT00667082 | NPI-0052 and Vorinostat in Patients With Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma | Non-Small Cell Lung Cancer; Pancreatic Cancer; Melanoma; Lymphoma; Multiple Myeloma | Phase 1 | Treatment |
| NCT00629473 | A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies | Advanced Cancer | Phase 1 | Treatment |
| NCT03345095 | A Phase III Trial of Marizomib in Combination With Standard Temozolomide-based Radiochemotherapy Versus Standard Temozolomide-based Radiochemotherapy Alone in Patients With Newly Diagnosed Glioblastoma | Newly Diagnosed Glioblastoma | Phase 3 | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
