MARIZOMIB

Investigational

Details

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

Structure Search

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

HIDE SMILES / InChI

Molecular Formula	C15H20ClNO4
Molecular Weight	313.777
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22978849

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

Targets

Primary Target	Pharmacology	Potency
Proteasome subunit beta type-2 3 Target ID: P49721 Gene ID: 5690.0 Gene Symbol: PSMB2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22978849	Inhibitor 8504	28.0 nM [IC50]
Proteasome subunit beta type-5 5 Target ID: P28074\|\|\|Q86T01 Gene ID: 5693.0 Gene Symbol: PSMB5 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22978849	Inhibitor 8504	3.5 nM [IC50]
Proteasome subunit beta type-1 3 Target ID: P20618 Gene ID: 5689.0 Gene Symbol: PSMB1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22978849	Inhibitor 8504	430.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00461045	Primary	Phase II 1147	Unknown Approved Use Unknown
Malignant glioma 10 Sources: https://www.clinicaltrials.gov/ct2/show/NCT02330562	Primary	Phase II 1147	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 438	Unknown Approved Use Unknown
Pancreatic adenocarcinoma 3 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 438	Unknown Approved Use Unknown
Melanoma 88 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 438	Unknown Approved Use Unknown
Lymphoma 60 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
30.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22080430/	0.7 mg/m² 1 times / week multiple, intravenous dose: 0.7 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		MARIZOMIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
34.53 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27117181	0.9 mg/m² 1 times / week multiple, intravenous dose: 0.9 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		MARIZOMIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
310.2 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22080430/	0.7 mg/m² 1 times / week multiple, intravenous dose: 0.7 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		MARIZOMIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.1 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22080430/	0.7 mg/m² 1 times / week multiple, intravenous dose: 0.7 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		MARIZOMIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
30 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27117181	0.9 mg/m² 1 times / week multiple, intravenous dose: 0.9 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		MARIZOMIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.9 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 0.9 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 0.9 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	DLT: Gait disturbance, Insomnia... Dose limiting toxicities: Gait disturbance (50%) Insomnia (50%) Hallucination visual (50%) Feeling drunk (50%) Sources: https://pubmed.ncbi.nlm.nih.gov/27117181
0.5 mg/m2 2 times / week multiple, intravenous MTD Dose: 0.5 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 0.5 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	Sources: https://pubmed.ncbi.nlm.nih.gov/27117181
0.7 mg/m2 1 times / week multiple, intravenous MTD Dose: 0.7 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 0.7 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	Sources: https://pubmed.ncbi.nlm.nih.gov/27117181
0.7 mg/m2 1 times / week multiple, intravenous RP2D Dose: 0.7 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 0.7 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27009059	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27009059	DLT: Confusional state, Hallucinations... Dose limiting toxicities: Confusional state (grade 3, 7.7%) Hallucinations (grade 2, 7.7%) Mental status changes (grade 3, 7.7%) Balance disorder (grade 3, 7.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/27009059
0.5 mg/m2 2 times / week multiple, intravenous Studied dose Dose: 0.5 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 0.5 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	DLT: Hallucination visual, Cognitive disorder... Dose limiting toxicities: Hallucination visual (grade 3, 11.1%) Cognitive disorder (grade 3, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/27117181
0.6 mg/m2 2 times / day multiple, intravenous Studied dose Dose: 0.6 mg/m2, 2 times / day Route: intravenous Route: multiple Dose: 0.6 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	DLT: Visual disturbance, cognitive impairmen... Dose limiting toxicities: Visual disturbance (grade 1, 25%) cognitive impairmen (grade 3, 25%) Orientation disturbe (grade 3, 25%) Unsteady gait (grade 3, 25%) Auditory hallucinations (grade 3, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/27117181
0.8 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 0.8 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 0.8 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	DLT: Dizziness, Hallucination... Dose limiting toxicities: Dizziness (33.3%) Hallucination (33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/27117181

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	MRP 9 P-gp 2052

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP 9	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21303921/	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28676669/	weak

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	2531AH	https://aksci.com/item_detail.php?cat=2531AH
ApexBio Technology	A4010	https://www.apexbt.com/catalogsearch/result/?q=A4010
BLD Pharm	BD284709	http://www.bldpharm.com/search/Search.html?keyword=BD284709
Cayman Chemical	10007311	http://www.caymanchem.com/app/template/Product.vm/catalog/10007311
Chem Scene	CS-0002986	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0002986
eMolecules	49383303	https://orderbb.emolecules.com/search/#?query=49383303
mcule	MCULE-2585874528	https://mcule.com/MCULE-2585874528/
MedChem Express	HY-10985	https://www.medchemexpress.com/search.html?q=HY-10985&ft=&fa=&fp=
Molnova	M14488	https://www.molnova.com/en/serch-list.html?keywords=M14488
MolPort	MolPort-035-395-768	https://www.molport.com/shop/molecule-link/MolPort-035-395-768
Toronto Research Chemicals	C991908	https://www.trc-canada.com/product-detail/?CatNum=C991908

PubMed

Title	Date	PubMed
[The teaching of epidemiology in Italy].	1988-12	2978849

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:03:47 GMT 2025` Edited by `admin` on `Mon Mar 31 18:03:47 GMT 2025`
Record UNII	703P9YDP7F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SALINOSPORAMIDE A

Preferred Name

English

MARIZOMIB

Official Name

English

marizomib [INN]

Common Name

English

6-OXA-2-AZABICYCLO(3.2.0)HEPTANE-3,7-DIONE, 4-(2-CHLOROETHYL)-1-((S)-(1S)-2-CYCLOHEXEN-1-YLHYDROXYMETHYL)-5-METHYL-, (1R,4R,5S)-

Systematic Name

English

MARIZOMIB [USAN]

Common Name

English

NPI-0052

Code

English

(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

Systematic Name

English

SALINOSPORAMIDE A [MI]

Common Name

English

Marizomib [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2160