MARIZOMIB

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

[H][C@@]1(CCCC=C1)[C@H](O)[C@@]23NC(=O)[C@H](CCCl)[C@]2(C)OC3=O

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 8297	28.0 nM [IC50]
Proteasome subunit beta type-5 6 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 8297	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 8297	430.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00461045	Primary	Phase II 1132	Unknown Approved Use Unknown
Malignant glioma 10 Sources: https://www.clinicaltrials.gov/ct2/show/NCT02330562	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 428	Unknown Approved Use Unknown
Pancreatic adenocarcinoma 3 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 428	Unknown Approved Use Unknown
Melanoma 88 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 428	Unknown Approved Use Unknown
Lymphoma 58 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00667082	Primary	Phase I 428	Unknown Approved Use 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 Page: p.4563	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563	DLT: Insomnia, Hallucination visual... Dose limiting toxicities: Insomnia (50%) Hallucination visual (50%) Gait disturbance (50%) Feeling drunk (50%) Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563
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 Page: p.4563	unhealthy, ADULT n = 10 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563	Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563
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 Page: p.4563	unhealthy, ADULT n = 12 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563	Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563
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 n = 13 Health Status: unhealthy Condition: multiple myeloma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/27009059	DLT: Confusional state, Balance disorder... Dose limiting toxicities: Confusional state (grade 3, 7.7%) Balance disorder (grade 3, 7.7%) Hallucinations (grade 2, 7.7%) Mental status changes (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 Page: p.4563	unhealthy, ADULT n = 9 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563	DLT: Cognitive disorder, Hallucination visual... Dose limiting toxicities: Cognitive disorder (grade 3, 11.1%) Hallucination visual (grade 3, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563
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 n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/27117181	DLT: cognitive impairmen, Auditory hallucinations... Dose limiting toxicities: cognitive impairmen (grade 3, 25%) Auditory hallucinations (grade 3, 25%) Unsteady gait (grade 3, 25%) Visual disturbance (grade 1, 25%) Orientation disturbe (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 Page: p.4563	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563	DLT: Dizziness, Hallucination... Dose limiting toxicities: Dizziness (33.3%) Hallucination (33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/27117181 Page: p.4563

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	MRP 7 P-gp 1537

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP 7	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21303921/	no
P-gp 1537	substrate 3367 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
MedChem Express	HY-10985	https://www.medchemexpress.com/search.html?q=HY-10985&ft=&fa=&fp=
MolPort	MolPort-035-395-768	https://www.molport.com/shop/molecule-link/MolPort-035-395-768
Molnova	M14488	https://www.molnova.com/en/serch-list.html?keywords=M14488
Toronto Research Chemicals	C991908	https://www.trc-canada.com/product-detail/?CatNum=C991908
eMolecules	49383303	https://orderbb.emolecules.com/search/#?query=49383303
mcule	MCULE-2585874528	https://mcule.com/MCULE-2585874528/

PubMed

Title	Date	PubMed

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 `Fri Dec 15 15:38:07 UTC 2023` Edited by `admin` on `Fri Dec 15 15:38:07 UTC 2023`
Record UNII	703P9YDP7F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MARIZOMIB

Official Name

English

marizomib [INN]

Common Name

English

SALINOSPORAMIDE A

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