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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H29N3O5
Molecular Weight 331.4079
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MARIMASTAT

SMILES

CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO)C(C)(C)C

InChI

InChIKey=OCSMOTCMPXTDND-OUAUKWLOSA-N
InChI=1S/C15H29N3O5/c1-8(2)7-9(10(19)13(21)18-23)12(20)17-11(14(22)16-6)15(3,4)5/h8-11,19,23H,7H2,1-6H3,(H,16,22)(H,17,20)(H,18,21)/t9-,10+,11-/m1/s1

HIDE SMILES / InChI

Molecular Formula C15H29N3O5
Molecular Weight 331.4079
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Marimastat is a broad spectrum matrix metalloprotease (MMP) inhibitor. It is an angiogenesis and metastasis inhibitor. It mimics the peptide structure of natural MMP substrates and binds to matrix metalloproteases, thereby preventing the degradation of the basement membrane by these proteases. This antiprotease action prevents the migration of endothelial cells needed to form new blood vessels. Inhibition of MMPs also prevents the entry and exit of tumor cells into existing blood cells, thereby preventing metastasis. Marimastat has been in pivotal phase III trials in glioblastoma, breast, ovarian and small and non-small cell lung cancer, but these trials have all been discontinued because marimastat failed to show superior efficacy over either standard chemotherapy or placebo.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
1.1 nM [Ki]
84.0 nM [Ki]
11.0 nM [Ki]
0.4 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
108.2 μg/L
25 mg single, oral
MARIMASTAT plasma
Homo sapiens
1965.8 μg/L
800 mg single, oral
MARIMASTAT plasma
Homo sapiens
540 ng/mL
100 mg 2 times / day steady-state, oral
MARIMASTAT plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
606 μg × h/L
25 mg single, oral
MARIMASTAT plasma
Homo sapiens
13765.9 μg × h/L
800 mg single, oral
MARIMASTAT plasma
Homo sapiens
2623 ng × h/mL
100 mg 2 times / day steady-state, oral
MARIMASTAT plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
7.5 h
25 mg single, oral
MARIMASTAT plasma
Homo sapiens
7 h
800 mg single, oral
MARIMASTAT plasma
Homo sapiens
4.9 h
100 mg 2 times / day steady-state, oral
MARIMASTAT plasma
Homo sapiens

Doses

AEs

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Patients received marimastat 10 mg bid.
Route of Administration: Oral
In Vitro Use Guide
Marimastat (100 nM) significantly inhibits the expression of metalloproteinase 14 in U251, U87, GBM39, and GBM43 tumor cells. Marimastat specifically inhibits the growth of glioma cells and has no effect on normal human astrocytes.
Substance Class Chemical
Record UNII
D5EQV23TDS
Record Status Validated (UNII)
Record Version