MARIMASTAT

Investigational

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 Search

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

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.hmdb.ca/metabolites/HMDB0014924 | https://www.ncbi.nlm.nih.gov/pubmed/12757409

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 Target	Pharmacology	Potency
Matrix metalloproteinase-1 8 Target ID: CHEMBL332 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12873504	Inhibitor 8504	1.1 nM [Ki]
Matrix metalloproteinase 3 13 Target ID: CHEMBL283 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12873504	Inhibitor 8504	84.0 nM [Ki]
Matrix metalloproteinase 9 20 Target ID: CHEMBL321 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12873504	Inhibitor 8504	11.0 nM [Ki]
ADAM17 3 Target ID: CHEMBL3706 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12873504	Inhibitor 8504	0.4 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15570070	Primary	Phase III 665	Unknown Approved Use Unknown
Metastatic breast cancer 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12757409	Primary	Phase III 665	Unknown Approved Use Unknown
Small-cell lung cancer 41 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12757409	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
108.2 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9489589/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	MARIMASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1965.8 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9489589/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	MARIMASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
540 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9626215	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	MARIMASTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
606 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9489589/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	MARIMASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
13765.9 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9489589/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	MARIMASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2623 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9626215	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	MARIMASTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
7.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9489589/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	MARIMASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9489589/	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	MARIMASTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9626215	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	MARIMASTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9626215	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9626215	DLT: Inflammatory polyarthritis... Other AEs: Myalgia, Edema... Dose limiting toxicities: Inflammatory polyarthritis (1 pt) Other AEs: Myalgia (grade 3, 2 patients) Edema (grade 2, 2 patients) Fatigue (grade 2, 1 pt) Hepatic toxicity (grade 2, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/9626215
20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	DLT: Arthralgia... Dose limiting toxicities: Arthralgia (grades 3-4, 42.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/15958628
40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	DLT: Arthralgia... Dose limiting toxicities: Arthralgia (grades 3-4, 88.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/15958628
5 mg 1 times / day multiple, oral Studied dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	DLT: Arthralgia... Dose limiting toxicities: Arthralgia (grades 3-4, 5.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/15958628

AEs

AE	Significance	Dose	Population
Inflammatory polyarthritis	1 pt DLT, Disc. AE	100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9626215	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9626215
Fatigue	grade 2, 1 pt	100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9626215	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9626215
Hepatic toxicity	grade 2, 1 pt	100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9626215	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9626215
Edema	grade 2, 2 patients	100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9626215	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9626215
Myalgia	grade 3, 2 patients	100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9626215	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9626215
Arthralgia	grades 3-4, 42.9% DLT	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15958628
Arthralgia	grades 3-4, 88.9% DLT	40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15958628
Arthralgia	grades 3-4, 5.9% DLT	5 mg 1 times / day multiple, oral Studied dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15958628	unhealthy Health Status: unhealthy Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15958628

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087 substrate 1946

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/12942041/	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12942041/	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12942041/	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P007Y8Y	https://www.1pchem.com/search?query=1P007Y8Y
AK Scientific	3803AH	https://aksci.com/item_detail.php?cat=3803AH
Alfa Chemistry	ACM154039608	http://www.alfa-chemistry.com/search.aspx?q=ACM154039608
AOBIOUS INC	AOB5057	http://aobious.com/aobious/search?search_query=AOB5057
ApexBio Technology	A4049	https://www.apexbt.com/catalogsearch/result/?q=A4049
AstaTech	F17409	http://astatechinc.com/CPSResult.php?CRNO=F17409
BLD Pharm	BD225980	http://www.bldpharm.com/search/Search.html?keyword=BD225980
BOC Sciences	154039-60-8	http://www.bocsci.com/description.asp?cas=154039-60-8
Chem Scene	CS-3456	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3456
ChemShuttle	141867	https://www.chemshuttle.com/catalogsearch/result/?q=141867
Debye Scientific	DB-064014	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-064014
eMolecules	195291884	https://orderbb.emolecules.com/search/#?query=195291884
eMolecules	31634939	https://orderbb.emolecules.com/search/#?query=31634939
Excenen	EX-A643	http://www.excenen.com/searchresultlist.php?id=EX-A643
KeyOrganics	AS-57129	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-57129
Lab Network	LN01286816	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01286816
mcule	MCULE-5291153045	https://mcule.com/MCULE-5291153045/
mcule	MCULE-9966474465	https://mcule.com/MCULE-9966474465/
MedChem Express	HY-12169	https://www.medchemexpress.com/search.html?q=HY-12169&ft=&fa=&fp=
Molnova	M12177	https://www.molnova.com/en/serch-list.html?keywords=M12177
MolPort	MolPort-006-167-635	https://www.molport.com/shop/molecule-link/MolPort-006-167-635
Selleck Chemicals	S7156	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7156
TargetMol	T6885	https://www.targetmol.com/search?keyword=T6885
Tocris	2631	https://www.tocris.com/search.php?Type=QuickSearch&Value=2631
Wonderchem	WD059T6	http://www.wonder-chem.com/search.html?text=WD059T6

PubMed

Title	Date	PubMed
Gastric cancer. Treatment of advanced disease and new drugs.	2005-09-01	15970566
Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases.	2005-07-15	15950618
Marimastat in the treatment of patients with biochemically relapsed prostate cancer: a prospective randomized, double-blind, phase I/II trial.	2005-06-15	15958628
The effect of marimastat, a metalloprotease inhibitor, on allergen-induced asthmatic hyper-reactivity.	2005-06-01	15893540
Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.	2005-05-01	15867243
Matrix metalloproteinase inhibition impairs the processing, formation and mineralization of dental tissues during mouse molar development.	2005-04-01	15748894
Docetaxel in the management of advanced pancreatic cancer.	2005-04	16015551
Analysis of combination anti-angiogenesis therapy on markers of coagulation, platelet activation and angiogenesis in patients with advanced cancer.	2005-03-10	15723715
Macrophage elastase (MMP-12): a pro-inflammatory mediator?	2005-03	15962117
Epidermal growth factor receptor-dependent and -independent pathways in hydrogen peroxide-induced mitogen-activated protein kinase activation in cardiomyocytes and heart fibroblasts.	2005-03	15574683
ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage.	2004-12-03	15381692
Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196.	2004-12-01	15570070
Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.	2004-11-01	15354209
Decreased production of collagen Type III in cultured smooth muscle cells from varicose vein patients is due to a degradation by MMPs: possible implication of MMP-3.	2004-10-19	16088212
Phase II study of a triplet regimen in advanced colorectal cancer using methotrexate, oxaliplatin and 5-fluorouracil.	2004-10-18	15381935
Molecular neuro-oncology and the development of targeted therapeutic strategies for brain tumors. Part 3: brain tumor invasiveness.	2004-10	15485315
SRC family kinases mediate epidermal growth factor receptor ligand cleavage, proliferation, and invasion of head and neck cancer cells.	2004-09-01	15342401
Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer.	2004-07-05	15162145
Synthesis of marimastat and a marimastat conjugate for affinity chromatography and surface plasmon resonance studies.	2004-05-20	15149188
Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera.	2004-04-05	15054465
Novel therapies for pancreatic adenocarcinoma.	2004-04	15191689
Involvement of matrix metalloproteinases in the onset of dentin mineralization.	2004-04	15056115
ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma.	2004-03-08	14997207
Matrix metalloproteinase inhibitors.	2004-03	14751086
A phase I and pharmacological study of the matrix metalloproteinase inhibitor BB-3644 in patients with solid tumours.	2004-02-23	14970856
Crystal structure of the catalytic domain of human ADAM33.	2004-01-02	14659745
[Expression of matrix metalloproteinases in patients with malignant tumors].	2004	15630339
Recent translational research: antiangiogenic therapy for breast cancer - where do we stand?	2004	15084233
Levels and molecular forms of MMP-7 (matrilysin-1) and MMP-8 (collagenase-2) in diseased human peri-implant sulcular fluid.	2003-12	14632921
Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer.	2003-12	14611919
Comparison of prognostic factors in patients in phase I trials of cytotoxic drugs vs new noncytotoxic agents.	2003-10-06	14520440
[Angiogenesis and metastasis in colorectal cancer].	2003-09	14574863
Anti-angiogenesis in cancer therapy.	2003-08	12962008
A phase I and pharmacologic study of the combination of marimastat and paclitaxel in patients with advanced malignancy.	2003-08	12942041
Angiogenesis inhibitors under study for the treatment of lung cancer.	2003-08	12867064
Functional characterization of adherent synovial fluid cells in rheumatoid arthritis: destructive potential in vitro and in vivo.	2003-07	12847681
In vitro and in vivo endochondral bone formation models allow identification of anti-angiogenic compounds.	2003-07	12819020
The interaction of metal ions and Marimastat with matrix metalloproteinase 9.	2003-06-01	12763661
Broad-spectrum matrix metalloproteinase inhibitor marimastat-induced musculoskeletal side effects in rats.	2003-06	12794843
Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura.	2003-05-19	12771921
Emerging drugs for non-small cell lung cancer.	2003-05	14610920
Advances in molecular therapies in patients with brain tumors.	2003-04-25	12712007
Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy.	2003-04-22	12698191
[Matrix metalloproteinases and atherosclerosis. Therapeutic aspects].	2003-04-19	12702469
Gateways to clinical trials.	2003-04-15	12690708
Randomised double blind placebo control study of adjuvant treatment with the metalloproteinase inhibitor, Marimastat in patients with inoperable colorectal hepatic metastases: significant survival advantage in patients with musculoskeletal side-effects.	2003-04-12	12680160
Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition.	2003	14524532
Marimastat: BB 2516, TA 2516.	2003	12757409
Drugs in development: bisphosphonates and metalloproteinase inhibitors.	2003	12716443
The role of the matrix metalloproteinases during in vitro vessel formation.	2002	12831062

Patents

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 Created by `admin` on `Mon Mar 31 18:11:57 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:57 GMT 2025`
Record UNII	D5EQV23TDS
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BB-2516

Preferred Name

English

MARIMASTAT

Official Name

English

KB-R 8898

Code

English

GI-5712

Code

English

GI5712

Code

English

TA2516

Code

English

MARIMASTAT [MART.]

Common Name

English

MARIMASTAT [USAN]

Common Name

English

NSC-719333

Code

English

TA-2516

Code

English

MARIMASTAT [MI]

Common Name

English

BB2516

Code

English

BUTANEDIAMIDE, N(SUP 4)-(2,2-DIMETHYL-1-((METHYLAMINO)CARBONYL)PROPYL)-N1,2-DIHYDROXY-3-(2-METHYLPROPYL)-, (2S-(N4(R*),2R*,3S*))-

Common Name

English

marimastat [INN]

Common Name

English

(2S,3R)-3-[[(1S)-2,2-Dimethyl-1-(methylcarbamoyl)propyl]carbamoyl]-2-hydroxy-5-methylhexanohydroxamic acid

Systematic Name

English

Marimastat [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1970