ILOMASTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H28N4O4
Molecular Weight	388.4607
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(C)C)CC(=O)NO

InChI

InChIKey=NITYDPDXAAFEIT-DYVFJYSZSA-N

InChI=1S/C20H28N4O4/c1-12(2)8-13(10-18(25)24-28)19(26)23-17(20(27)21-3)9-14-11-22-16-7-5-4-6-15(14)16/h4-7,11-13,17,22,28H,8-10H2,1-3H3,(H,21,27)(H,23,26)(H,24,25)/t13-,17+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H28N4O4
Molecular Weight	388.4607
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1322694 | https://www.ncbi.nlm.nih.gov/pubmed/29088927 | https://www.ncbi.nlm.nih.gov/pubmed/28692737

Ilomastat (also known as galardin or GM 6001) is a broad-spectrum matrix metalloproteinase inhibitor. It is a member of the hydroxamic acid class of reversible metallopeptidase inhibitors. The hydroxamic acid binds the catalytic zinc(2+) ion in a bidentate manner, blocking substrate access to the active site and rendering the metal incapable of peptide hydrolysis. Preclinical studies have shown that ilomastat can inhibit conjunctival scarring after glaucoma filtration surgery in rabbits, in lens capsules following simulated cataract surgery, and in models of vitreoretinal contraction.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Matrix metalloproteinase-1 8 Target ID: CHEMBL332 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8504	3.3 nM [IC50]
Matrix metalloproteinase-2 13 Target ID: CHEMBL333 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8504	10.0 nM [IC50]
Matrix metalloproteinase 3 13 Target ID: CHEMBL283 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8504	7.0 nM [IC50]
Matrix metalloproteinase 7 3 Target ID: CHEMBL4073 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8504	33.0 nM [IC50]
Matrix metalloproteinase 8 6 Target ID: CHEMBL4588 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17623656	Inhibitor 8504	9.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

PubMed

Title	Date	PubMed
Action of hexachlorobenzene on tumor growth and metastasis in different experimental models.	2013-05-01	23462309
Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption.	2013-05	23525277
Characterisation of acetylcholinesterase release from neuronal cells.	2013-03-25	23047022
Proteolysis controls endogenous substance P levels.	2013	23894327
Autocrine effect of EGFR ligands on the pro-inflammatory response induced by PM(2.5) exposure in human bronchial epithelial cells.	2012-10	22581348
A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells.	2012-01-15	22155090
Permissive effect of EGFR-activated pathways on RVI and their anti-apoptotic effect in hypertonicity-exposed mIMCD3 cells.	2011-12	21568938
Zinc-triggered induction of tissue plasminogen activator by brain-derived neurotrophic factor and metalloproteinases.	2011-09	21615740
Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1.	2010-09-01	20660715
Ovarian steroids, mitogen-activated protein kinases, and/or aspartic proteinases cooperate to control endometrial remodeling by regulating gene expression in the stroma and glands.	2010-09	20660070
ATP induced microglial cell migration through non-transcriptional activation of matrix metalloproteinase-9.	2010-02	20195827
Potent homocysteine-induced ERK phosphorylation in cultured neurons depends on self-sensitization via system Xc(-).	2010-01-15	19850060
Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production.	2009-11-01	19661247
Chronic treatment of astrocytes with therapeutically relevant fluoxetine concentrations enhances cPLA2 expression secondary to 5-HT2B-induced, transactivation-mediated ERK1/2 phosphorylation.	2009-11	19662385
Evaluation of protease inhibitors and an antioxidant for treatment of sulfur mustard-induced toxic lung injury.	2009-09-01	18852015
Fluoxetine-mediated 5-HT2B receptor stimulation in astrocytes causes EGF receptor transactivation and ERK phosphorylation.	2008-12	18758753
Expression profiles of matrix metalloproteinase 9 in teleost fish provide evidence for its active role in initiation and resolution of inflammation.	2008-12	18557954
Protective effect of ilomastat on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats.	2008-10-07	18837084
Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation.	2008-09-23	18787115
Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production.	2008-04	18006877
Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by diverse classes of metal ligands.	2007-11-01	17680773
Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects.	2007-09-21	17623656
Methylmercury induces activation of Notch signaling.	2006-12	16757030
Effects of alpha1D-adrenergic receptors on shedding of biologically active EGF in freshly isolated lacrimal gland epithelial cells.	2006-11	16760267
Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a PKCdelta-dependent pathway in murine lung.	2006-05	16571779
Src homology 2-containing phosphotyrosine phosphatase regulates endothelin-1-induced epidermal growth factor receptor transactivation in rat renal tubular cell NRK-52E.	2006-04	16261333
Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases.	2005-11	16279945
Selective inhibition of TNF-alpha-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib.	2005-05-09	15841081
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
Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation.	2005-02-15	15531749
Structure-based virtual screening and biological evaluation of potent and selective ADAM12 inhibitors.	2004-12-20	15546732
Heparin-binding epidermal growth factor cleavage mediates zinc-induced epidermal growth factor receptor phosphorylation.	2004-04	12972402
Tetrahydroisoquinoline based sulfonamide hydroxamates as potent matrix metalloproteinase inhibitors.	2004-01-05	14684295
Tamoxifen induces apoptosis in Fas+ tumor cells by upregulating the expression of Fas ligand.	2003-04	12721755
Decreased expression of membrane IL-5 receptor alpha on human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated process.	2002-12-01	12444155
Inhibition of human skin fibroblast collagenase, thermolysin, and Pseudomonas aeruginosa elastase by peptide hydroxamic acids.	1992-08-11	1322694

Patents

Sample Use Guides

In Vivo Use Guide

Rabbits received 0.1 mL of 100 uM ilomastat.

Route of Administration: Other

In Vitro Use Guide

Ilomastat inhibits human skin fibroblast collagenase with Ki of 0.4 nM when assayed with a synthetic thioester substrate at pH 6.5, with 50-fold selectivity over two bacterial enzymes, thermolysin, and Pseudomonas aeruginosa elastase.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:42:39 GMT 2025` Edited by `admin` on `Wed Apr 02 08:42:39 GMT 2025`
Record UNII	I0403ML141
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ILOMASTAT

Official Name

English

GM6001

Preferred Name

English

(R)-N(SUP 1)-HYDROXY-N-((S)-2-INDOL-3-YL-1-(METHYLCARBAMOYL)ETHYL)-2-ISOBUTYLSUCCINAMIDE

Systematic Name

English

ilomastat [INN]

Common Name

English

GALARDIN

Common Name

English

ILOMASTAT [USAN]

Common Name

English

(S-(R*,S*))-N(SUP 4)-HYDROXY-N(SUP 1)-(1H-INDOL-3-YLMETHYL)-2-(METHYLAMINO)-2-OXOETHYL)-2-(2-METHYLOPROPYL)BUTANEDIAMIDE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

63991