Marizomib

DRACPC ID  DRACPC0092

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

Type  Small Molecule

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

Structure

 

Show IUPAC/InChI/SMILES

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.





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